Dual properties of PEGDA-GelMA scaffold: Good long-term cerebral biocompatibility and motor outcome but limited potential for brain regeneration

Dual properties of PEGDA-GelMA scaffold: Good long-term cerebral biocompatibility and motor outcome but limited potential for brain regeneration | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Dual properties of PEGDA-GelMA scaffold: Good long-term cerebral biocompatibility and motor outcome but limited potential for brain regeneration Maylis Combeau, Vincent Lanternier, Adrien Brilhault, Julien Clauzel, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8711671/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract BACKGROUND Acute brain injuries represent a major clinical challenge, as current therapeutic strategies are insufficient to promote tissue regeneration and fully restore lost neurological functions. In this context, biomaterials have shown promise in promoting tissue repair. METHODS This study introduces an innovative strategy involving the 3D DLP (Digital Light Processing) printing of a degradable scaffold composed of PEGDA (polyethylene ‑glycol diacrylate) and GelMA (gelatin methacryloyl). The neuro‑implant combines the mechanical stability of PEGDA with the bioactivity and biocompatibility of gelatin, forming a porous and guiding architecture. This scaffold is implanted in rat brains injured by malonate injection. RESULTS DLP technology enabled the complex scaffold architecture specific to the cortex. A longitudinal follow‑up using behavioural assays and MR imaging at 3‑ and 6‑months post‑injury revealed a favourable in ‑vivo safety profile, contralesional functional MR activation, and improved grip strength of the impaired forelimb at 6 months (p = 0.057). MRI provided high‑quality images revealing the scaffold’s fine architecture in vivo and showed no degradation. Histological analysis confirmed chronic biocompatibility, with complete colonisation by viable endogenous cells, including a stable vascular network persisting at 6 months and a high density of neural progenitors (Sox2⁺, Dcx⁺) and mature oligodendrocytes (OSP⁺), offset by a surprising absence of mature, functional neurons and astrocytes. CONCLUSION Our results highlight the long‑term biocompatibility of the PEGDA–GelMA scaffold in the brain, but its functional regenerative potential is limited. Nevertheless, this implant appears capable of improving functional motor outcome; this improvement was not explained by neuron or astrocyte attraction. PEGDA–GelMA can serve as a structural bridge between healthy and damaged brain tissue, attracting endogenous cells. The implant stabilises the lesion site and may enhance brain plasticity mechanisms such as contralesional motor ‑cortex involvement. These findings provide an acellular basis for developing a regenerative, brain‑compatible structural platform targeting central nervous system lesions. 3D DLP printing PEGDA GelMA Tissue bioengineering Acute brain injury MRI Behaviour Brain repair Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Highlights • Long‑term biocompatibility of a PEGDA–GelMA scaffold implanted in the injured rat brain • Controlled degradation and structural stability of a PEGDA–GelMA scaffold over 6 months • A 3D DLP ‑printed PEGDA–GelMA scaffold without cells sustains significant colonisation • PEGDA–GelMA scaffold enables cell colonisation and vascularisation by host cells • PEGDA–GelMA scaffold promotes functional recovery at 6 months post‑injury Introduction Regenerative medicine aims to restore lost or impaired tissue functions by harnessing endogenous repair mechanisms and/or employing bioengineered substitutes [1]. Recent advances in bioengineering have led to the development of implantable biomaterial-based strategies capable of providing structural and bioactive support to promote cell adhesion, proliferation, migration, differentiation, and survival [2, 3]. Among these approaches, biomimetic scaffolds seek to replicate the extracellular matrix (ECM) and create a favourable environment for tissue regeneration [4]. The integration of advanced technologies, such as computer-aided design (CAD) and 3D bioprinting now enables the fabrication of complex, physiologically relevant structures with precision [5]. These constructs can not only reproduce the mechanical and biochemical properties of the ECM but also deliver cells and biomolecules in a spatially controlled manner [6, 7]. In the central nervous system, such architectures can help guide axonal regeneration by directing neurons toward their targets, thereby promoting reconnection between injured and healthy tissue [8]. To ensure optimal integration, long-term stability, and sustained functional repair, the use of biodegradable or bioeliminable materials is essential to allow complete cellular repopulation of the lesion site [9, 10]. Natural biomaterials offer excellent biocompatibility, biodegradability, and low cytotoxicity, but their application is hindered by insufficient mechanical strength required for implantation and tissue support [11]. In contrast, synthetic polymers provide better structural integrity but are less biocompatible and often require functionalisation with adhesion sites [12]. Thus, combining natural and synthetic polymers emerges as a promising strategy to balance biological compatibility with tunable mechanical and structural properties. Our preliminary studies have demonstrated the safety and non-toxicity of intracerebral implantation of PEGDA-GelMA in the short term [5, 13]. In the brain, it showed good stability and attractiveness at 1month post-injury, without eliciting a significant inflammatory response; it was colonised by a diversified population of neural progenitor cells and exhibited proper vascularization [13]. PEGDA-GelMA is a strategic hybrid hydrogel that blends synthetic and natural components. PEGDA belongs to the category of chemical hydrogels with high stability but low biological activity and compatibility [5, 14–16], while gelatin is a natural hydrogel with biomimetic relevance, essential biological components, and good cell signaling thanks to its RGD (Arginine-Glycine-Aspartic Acid) motifs [17]. To be photoprintable and acquire sufficient mechanical strength, it must be methacrylated. Together, these two biomaterials are mutually beneficial and form a promising combination for therapeutic applications in brain repair. To confirm and reinforce the potentially beneficial role of this biomaterial in brain regeneration, we set out to evaluate the biocompatibility and long-term regenerative capacity of PEGDA-GelMA in the rat brain. The resin was printed by digital light processing (DLP) into a 3D scaffold tailored to the targeted cortical anatomy. Because the degradation kinetics of PEGDA-GelMA in the brain tissue have not been described precisely, the first aim of this study was to determine its medium- and long-term stability and its degradation profile. The brain injury model validated by our group [5, 18–21] involves injection of a toxin, malonate, into the motor cortex, producing significant tissue damage and functional deficits. We also investigated the intrinsic biocompatibility kinetics of PEGDA-GelMA. Subsequently, we characterized its attractiveness at 3 and 6 months paying particular attention to the neurogenic niche, cell migration to the lesion zone, and the evolution of the neo-tissue formed within the scaffold over time. Finally, functionality was assessed by behavioural motors tests and functional MRI at 3 and 6 months. Materials and Methods Scaffold design As in previous studies, the scaffold was designed with Autodesk Fusion 360® computer‑aided design software. The structural objective was threefold: to guarantee porosity, to facilitate cellular infiltration, and to guide colonisation along three orthogonal directions using horizontal channels and vertical pillars (Fig. 3 ). We also had to ensure that the design could be inserted intracerebrally through a cranial flap with a maximum diameter of 5 mm. Lesion volumes were determined from post‑injury T2‑weighted MRI scans (see below for details). The CAD model is an adapted version of a patented brain-mimetic design [5]. While retaining its main features, the model was simplified to respect the printable resolution of PEGDA–GelMA resin. It consists of two parts: i) a top handle used for manipulation, and ii) a porous scaffold with channels and pillars of varying sizes (Fig. 3 ). The handle is surgically removed during implantation. PEGDA-GelMA scaffold preparation Scaffolds were printed on a LumenX™ 3D printer (CellInk Inc., Sweden), which uses DLP technology at 405 nm (violet) and offers a horizontal resolution of 50 µm (x,y). GelMA and PEGDA-200 Photo Ink™ (CellInk Inc.) were mixed in a 1:1 ratio. After photo-crosslinking, the modulus was about 22 ± 5 kPa for GelMA and 200 ± 20 kPa for PEGDA-200 (CellInk Inc). Prior to mixing, each ink was individually warmed to 37°C. The inks are supplied ready‑to‑use and require no additional additives. Printing parameters were: layer thickness 50 µm, initial exposure time 15 s, subsequent exposure 5 s; light output 20 mW cm⁻²; internal heating maintained at 75°C. Scaffold decontamination Before implantation, scaffolds underwent a decontamination procedure. They were rinsed three times (10 min each) with sterile Dulbecco’s phosphate‑buffered saline (PBS) and 1% penicillin–streptomycin (PenStrep, Gibco). The day before implantation, scaffolds were immersed in sterile 70% ethanol for 2 h at room temperature. They were then washed three times (3x 10 minutes) with PBS containing 1% PenStrep and stored overnight at 4°C. On the day of implantation, scaffolds were exposed to UV light for 30 min and stored in a sealed container with the same PBS/PenStrep solution. All decontamination steps followed Biosafety Level 2 guidelines. Animals Seventeen female Sprague‑Dawley rats (age 11 weeks; weight 280–320 g, Janvier Labs) were pair‑housed in enriched cages (30×18×32 cm). They were maintained at 20°C on a 12‑h light/12‑h dark cycle with ad libitum food and water. All procedures complied with EU Directive 2010/63 and were approved by the Direction Départementale de la Protection des Populations de la Haute‑Garonne and the Comité d’éthique pour l’expérimentation animale Midi‑Pyrénées (protocol n° APAFIS#22419‑2019101115259327v5). The 3Rs principles guided the minimal use of animals, and all experiments followed ARRIVE guidelines. The distribution of rats among groups is shown in Fig. 2 . At baseline: PEGDA–GelMA (P‑G) scaffold group (n = 8); Sham scaffold group (injured without implant, n = 8); sham lesion control (not injured, n = 1). P‑G and Sham rats received malonate‑induced brain injury. No sex differences were reported in this model [20, 21]. Half of the P‑G and Sham groups, plus the control rat, were sacrificed at 6 months; the others were sacrificed at 3 months. Some Sham rats exhibited hyper‑dilated ventricles that compressed the lesion, precluding histological analysis. These animals were excluded from that assessment. Two implanted rats were also excluded: one developed a head tumour and the other had a damaged, degraded scaffold after a second surgical suturing. Consequently, final group sizes for histology were reduced: at 3 months—P‑G (n = 3), Sham (n = 2); at 6 months—P‑G (n = 3), Sham (n = 2), control (n = 1). Results are presented as means ± SD. Motor function assessment Behaviour was monitored throughout the study to detect clinical signs and sensorimotor recovery. Motor function was evaluated at predetermined intervals using two tests previously validated by our team [5, 19, 22]: the Grip Strength Evaluation (maximum force exerted by each forelimb) and the Neurological Severity Scale (NSS). The measurement for each paw was conducted separately. The NSS comprises five tests focused on reflexes, stability, sensitivity, and mood; scores range from 0 to 16, with higher values indicating greater deficits. Brain injury induction Rats were anesthetised with isoflurane (3% induction, 2–3% maintenance) delivered at 0.7 L min⁻¹ O₂. They were placed in a stereotaxic frame (Bioseb lab). Pre‑medication consisted of intraperitoneal methylprednisolone (20 mg kg⁻¹, Centravet) and subcutaneous lidocaine (2%, 4 mg kg⁻¹, Centravet) for local scalp analgesia. The malonate model [19, 21] was used to induce the brain injury. One of the advantages of this technique is the ability to target key brain regions involved in human ischemic stroke, such as the sensorimotor cortex [20–22]. Malonate disrupts the Krebs cycle and respiratory chain enzymes, producing a chemical energy failure that mimics ischemic excitotoxicity with a penumbra [23–26]. Lesions were created by injecting 5 µL of a 3 M malonate solution (pH 7.4, PBS; Sigma‑Aldrich) into the motor cortex (M1) at coordinates 2.5 mm lateral and 0.5 mm anterior to Bregma, depth 2 mm [27]. The injured hemisphere corresponded to each rat’s dominant paw, as determined by grip strength. Malonate yields long‑term deficits suitable for therapeutic comparisons. Implantation Implantation and subsequent behavioural tests were performed blind. A second surgery was carried out on 16 rats 8 days post‑injury (peak neurogenesis [28]). Conditions matched the initial surgery. Scaffolds were inserted through a 5 mm cranial flap, removed, and repositioned at closure. Each injured rat received a wet PEGDA–GelMA scaffold (PBS‑filled pores). Eight rats had their scaffolds immediately removed (Sham group); the other eight retained them for the full protocol (P‑G group). In almost all animals, a synthetic cranial flap made of PCL pellets (CellInk) replaced the bone flap. The custom flap was fabricated in a 5 mm silicone mould to secure the hole, then sealed with dental cement. In vivo MRI Imaging used a 7 T preclinical scanner (Biospec 70/16, Bruker). A volume transmit coil and a 2×2 surface receiver were employed. Rats were positioned in a temperature‑regulated enclosure at 37°C and anaesthetised with Isoflurane/O₂ (1.5–2.5% adjusted to respiration). Anatomical T2 imaging used a Turbo‑RARE sequence (TE/TR = 35.7/5452 ms), producing coronal slices; volume matrix 256×256×48 voxels, resolution 0.137×0.137×0.500 mm³. Perfusion was acquired by pseudo‑continuous arterial spin labelling (pCASL) with cerebral blood flow maps (92×92×18 voxels, 0.326×0.326×0.9 mm³) combined with an inversion efficiency measure [29]. Functional BOLD imaging employed an echo‑planar sequence: TE = 11 ms, TR = 2000 ms, FOV = 30×30 mm², matrix 96×96 (resolution 313×313 µm²). Twenty‑one contiguous coronal slices (1 mm) were collected. Each run comprised 300 repetitions of 2 s with a block design (30 s stimulation/30 s rest); passive hindlimb stretching at 1 Hz, 2 N force was applied. Two 10-min runs per animal: contralesional first, then ipsilesional. fMRI data were analysed with SPM12 following standard preprocessing (slice‑timing, realignment, smoothing with a 0.625 mm FWHM Gaussian kernel). Three anatomical scans were performed at 24 h, 1 month, and 3 months post‑lesion; rats sacrificed at 6 months underwent an additional pre‑mortem scan. Lesions were manually segmented on T2 images with ITKsnap: volume was calculated taking into account atrophy and dilation of ventricles, as lesion volume + ipsilesional ventricule – contralesional ventricule [19]. Histology and immunofluorescence At 3 (n = 8) or 6 months (n = 9), animals received a lethal intraperitoneal injection of sodium pentobarbital (1 mL, 159 mg kg⁻¹, Centravet). Brain perfusion was performed with heparinised 0.9% NaCl (200 mL, 20 min) followed by 4% paraformaldehyde (250–300 mL, 40 min). Brains were post‑fixed in 10% buffered formalin for 24 h at 4°C and embedded in paraffin. Sections (8 µm thick) were cut with a Leica SM 2010R microtome; ~100 coronal sections per brain were obtained. Every twelfth section was stained H&E and Cresyl Violet acetate. Slides were examined on a Nikon Eclipse Ci and scanned (Panoramic 3D HISTEC). Sections at the lesion site were immunostained for GFAP (1:50, clone 6F2, Invitrogen) and Masson’s trichrome, an astrocytic marker, and Masson's Trichrome (a collagen fiber marker). For immunofluorescence, sections were identified using the Paxinos–Watson atlas [27]. Paraffin sections were deparaffinised, unmasked in Pt‑link low pH (K8005, Dako) for 30 min, then incubated in a humid chamber at room temperature for 30 min with a blocking buffer (1% BSA, Sigma‑Aldrich; 10% serum from donkey or goat, Thermo Fisher Scientific or Sigma-Aldrich, respectively). Primary antibodies were applied for 90 min (Table 1). After three 10‑min washes in PBS + 0.5% BSA, secondary antibodies conjugated to fluorochromes were incubated for 50 min at room temperature in the dark. Three additional 10‑min washes followed, then a fluorescent mounting medium with DAPI (Fluoroshield™, Sigma‑Aldrich) was applied. Images were captured on a Nikon Eclipse Ti2 and analysed with Fiji and Imaris. Statistical analysis Analyses were performed with GraphPad Prism 10. Behavioural data used non‑parametric tests; MRI data were analysed with linear mixed models. Each graph point represents one animal. Histological quantification involved 4–6 fields per rat from 2–3 sections. Statistical significance is indicated by asterisks, with the specific test detailed in each figure legend; non‑significant differences are marked “ns” or left unlabelled. Results Scaffold technical data The architecture shown in Fig. 3 was printed with patterns, spatial resolution and porosity suitable for tissue reconstruction. Cross‑sectional views (Fig. 3 ‑1D) of the CAD models allowed observation of the overall porous architecture, the organisation of interconnected layers and pillars, as well as the interior of the structures. Post‑printing photos (Fig. 3 ‑3AB) confirmed the porosity of the scaffolds and the removal of printing residues from pores and channels. Using an optical microscope we measured the one‑dimensional swelling of the scaffold in water; the average swelling was approximately 15.05 ± 2.8% (average 2‑D swellings of height and width, Suppl Fig. 1), comparable to previous findings with this material [5]. The average porosity was estimated at 53.78%, and the overall scaffold volume at 47.6 mm³ (values were computed from the 3D file and re‑adjusted with actual measurements of the printed scaffolds). It comprises a solid structure with a total volume of 22.03 mm³ and an empty, pore‑filled volume of 25.63 mm³. Compression tests performed on nine samples determined the deformation behaviour under increasing stress; the elastic modulus was estimated at 48 ± 10 kPa. This modulus renders the scaffold sufficiently rigid to support insertion into the injured brain and to withstand intracranial pressure, while also facilitating post‑impression rinses—necessary to remove photochemical waste—and decontamination baths prior to in vivo implantation without compromising its integrity. In vivo data Long-term sensorimotor improvement with PEGDA-GelMA scaffolds The cortico‑striatal lesion induced a motor deficit in the contralateral paw. Grip‑strength testing provided a sensitive, quantitative measure of forelimb strength; force was expressed in newtons and normalised to pre‑lesion reference values (Fig. 4 A). Post‑lesion performance of the contralateral forelimb showed a significant reduction (> 65%) in grip strength across all lesion groups (Sham scaffold: median = 31.5 ± 13.3%; P‑G scaffold: median = 31.3 ± 5.6%). In the early phase after implantation, the P‑G scaffold group exhibited a recovery profile similar to spontaneous recovery in Sham animals [5, 19, 20]. From the fourth month onward, spontaneous recovery in the Sham group slowed, reaching a plateau of ≈ 59.7 ± 7.9% over the four‑to‑six‑month period. Simultaneously, the P‑G scaffold curve exceeded that of the Sham group by a gain of 76.5 ± 4.8% at six months, yielding a trend toward significance (p = 0.057). Neurological deficits were evident, as shown by an NSS score of 12/16 (maximum deficit = 16) (Fig. 4 B). Both P‑G and Sham groups displayed similar spontaneous recovery over the following months, with no significant difference at six months. The sham‑injured animals (PBS injection without malonate) maintained relatively stable grip strength and NSS scores throughout the protocol, with only a slight transient decrease after control surgery. These findings suggest that P‑G scaffold implantation does not alter the early spontaneous motor recovery phase post‑brain injury; instead, therapeutic benefits on sensorimotor recovery appear to emerge in the chronic phase, beginning around month four and becoming more pronounced at six months. Longitudinal MRI follow-up As demonstrated in our previous safety and feasibility studies, T2w MRI imaging effectively monitors implanted scaffolds over one month [5, 13]. In this study we extended the longitudinal follow‑up to six months. The high spatial resolution of MRI (137 µm) allowed precise observation of the implant at both macroscopic (overall scaffold morphology and perilesional environment) and microstructural levels (identification of scaffold pores). Water-rich structures (PEGDA-GelMA hydrogels, damaged areas, and ventricles) appeared hyperintense on T2w images. Scaffold pores tended to be less hyperintense, healthy paranchyma regions displayed intermediate intensity, while white matter, periventricular, perilesional or peri-implant areas were hypointense (Fig. 5 A). These hypointensities near the implant and lesion arise from hypercellularity and may reflect migratory cells from the ventricle, thick glial scars, or collagen‑rich fibrotic tissue [5, 19]. At six months no thick hypointense rim was observed around the scaffold, suggesting an absence of dense glial scar or fibrosis. In implanted rats followed until six months, imaging revealed remarkable anatomical stability between the first and sixth months. Follow‑up images showed (i) no signs of rejection or encapsulation and (ii) preservation of scaffold shape, architecture, and porosity throughout the study period (Fig. 5 A). Scaffold volume matched lesion size: 51 ± 28 mm³ at one month for sham scaffolds and 66 ± 20 mm³ for P‑G scaffolds. Total lesion volumes (Fig. 5 A, first column; Fig. 5 B) increased significantly over time (p < 0.013), with progressive dilation of the ipsilateral ventricle in the Sham group between one and three months (*p = 0.02) and one and six months (**p = 0.009). This expansion was less pronounced in implanted animals, indicating a stabilising role of the scaffold in local brain architecture and in preventing ventricular dilation up to the skull. 3D volume reconstructions from MRI scans revealed average scaffold volumes of 52.6 ± 8.9 mm³ at one month, 47.5 ± 9.8 mm³ at three months, and 42.5 ± 4.4 mm³ at six months—consistent with the pre‑implantation volume (≈ 47.6 mm³) and suggesting no compression during implantation (Fig. 5 C). The average decrease over months was not significant (Fig. 5 C), and scaffold intensity remained unchanged, indicating temporal stability (Fig. 5 D). MR perfusion did not reveal cerebral blood flow within the scaffolds at three or six months; images resembled those obtained after one month [5]. Since P‑G scaffolds had not yet degraded at six months, they could not be replaced by sufficient vascularised tissue, rendering perfusion differences too subtle to detect. At three months, functional MRI showed localized activation within the scaffold in 2 of 8 implanted rats; this activation was absent at six months in one rat but a contralesional response appeared when moving the impaired limb. Perilesional activation was not observed in any animal. Frequently, movement of the paretic lower limb elicited activation in the contralesional sensorimotor cortex at the same position as for the healthy limb. Ex vivo data Long-term biocompatibility To assess scaffold stability and brain acceptance, we performed Masson’s trichrome staining (Fig. 6 ), measured glial scar thickness with GFAP immunostaining (Fig. 7 A–B), and quantified peri‑lesional microglia (Iba1+) (Fig. 7 C–D). The blue dye of Masson’s trichrome marks collagen fibres, allowing detection of fibro‑collagenous reactions after brain injury. In cases of poor biocompatibility or strong foreign ‑body reaction, a thick blue capsule may surround the implant. In our study we observed fine blue filaments within new tissue inside the scaffold and in the reconstructed tissue at the lesion edge in sham scaffolds at 3 and 6 months. These sparse collagen strands represent weak fibrosis or endogenous repair; they were unevenly distributed and did not impede tissue regeneration. At the interface between healthy host tissue and biomaterial, no collagen capsule formed after 3 or 6 months. Accumulation was more pronounced in tissues undergoing reconstruction within both sham and P‑G groups, particularly at the interface between neo‑tissue and biomaterial or between neo‑tissue and healthy tissue. A blue coloration proportional to maturity surrounded vessels supplying the damaged area; no significant inflammatory reaction exceeded that observed in one‑month safety studies [5, 13]. The glial scar appeared as a dense brown layer at the lesion edge and was measured at four equivalent sites (Fig. 7 A). Scar thickness at 3 and 6 months for sham and P‑G groups showed no significant differences between groups or over time, although a mild thinning trend emerged. At 3 months mean scar thickness was 23.45 µm (sham) and 26.67 µm (P‑G); at 6 months it decreased to 19.53 µm and 23.75 µm, respectively (Fig. 7 B). No astrocytes were detected beyond the glial barrier within the scaffold. The implantation of the scaffold over a 6-month period did not exacerbate the inflammatory response. Microglial analysis (Iba1) revealed no differences between groups (Fig. 7 C–D); time did not alter microglial activation, and slight scaffold degradation did not increase microglia numbers. Degradation of PEGDA-GelMA Histology confirmed MRI findings: the degradable scaffold remained intact at 3 and 6 months post‑implantation. Hematoxylin–eosin staining showed stable neural cytoarchitecture and cell colonisation within the scaffolds (Fig. 8 ). Indirect staining of PEGDA‑GelMA by HE or Masson’s trichrome is due to gelatin’s protein motifs (amine, carboxyl) that bind dyes and to the gel’s hydrophilic, porous nature. Depending on the section, we observed pillar‑like structures (Fig. 8 bottom right) or layered patterns (Fig. 8 top and bottom left). Dye affinity allowed monitoring of degradation over time. PEGDA‑GelMA was partially altered by dehydration, embedding and sectioning, producing artefacts such as folds or distortions; nevertheless, preserved areas revealed gradual gel volume loss characterised by gaps and reduced density. A “star‑shaped” pattern emerged: a denser, purple centre fading toward the periphery, suggesting centrifugal matrix degradation. Overall scaffold structure remained intact, with localized material loss rather than complete breakdown. Attractiveness of the PEGDA-GelMA scaffold Biocompatibility alone does not guarantee regenerative capacity; cellular attractiveness is also essential. We therefore assessed recruitment of neural progenitors and immature neuroblasts (Sox2 + and Dcx+) primarily from the subventricular zone (SVZ) after implantation (Fig. 9 A–B). Immunofluorescence images depict cell densities in the SVZ, lesion periphery, and core (with or without scaffold), highlighting endogenous repair. In the SVZ, time seemed to favor the production of immature neuroblasts. Sox2 + density decreased between 3 and 6 months in both groups (sham: 53%→34%; P‑G: 46%→41%), whereas Dcx+ remained stable or increased slightly (sham: 21%→22%; P‑G: 14%→22%). At the lesion periphery, Sox2 + and Dcx+ densities declined over time in sham animals but stayed stable in the P‑G group (sham: Sox2 + 35%→29%; Dcx + 5%→4%; P‑G: Sox2 + 35%→35%; Dcx + 5%→6%). Thus, peripheral attractiveness was better preserved with the P‑G scaffold. Within the lesion core, sham animals showed increased new cell populations over time (Sox2 + 14%→25%; Dcx + 0%→2%). In contrast, the P‑G group displayed a decrease in Sox2 + cells (25%→12%) and an increase in Dcx+ cells (2%→5%). Neuronal maturation was evaluated with β‑III tubulin (immature) and NeuN (mature). β‑III tubulin+ neurons were present but unevenly distributed; no NeuN+ cells were detected in reconstructed tissue for either group. Vascularisation, a key determinant of cell survival in issue undergoing reconstruction, was quantified using lectin staining, an endothelial marker. Both groups exhibited increased vascular density from 3 to 6 months (sham: 5%→8%; P‑G: 5%→6%). Oligodendrocyte numbers were assessed with the OSP(oligodendrocyte-specific protein) marker, a membrane marker of tight junctions. The P‑G scaffold group maintained higher oligodendrocyte densities, which remained stable between 3 and 6 months (sham: 3%→4%; P‑G: 5%→10%). Discussion In this in‑vivo study we describe the behaviour of a 3‑D PEGDA–GelMA scaffold implanted in an injured rat brain and followed longitudinally for up to 3 and 6 months. The work covers all stages of the project—from design and manufacture to non‑invasive in‑vivo evaluation and post‑mortem histological characterisation. Through dual‑kinetic monitoring we aimed to extract gradual data concerning the long‑term degradation of PEGDA–GelMA in brain tissue, which is currently unknown. Long‑term assessments are particularly relevant for studying chronic inflammation associated with biomaterials—especially in the CNS—and for evaluating their regenerative or scarring impact in an in‑vivo context [30, 31]. We demonstrated preservation of scaffold architecture over six months and a beginning of degradation. Our results show a trend toward improved grip strength. Generally, only scaffolds bearing cells or cellular secretome achieve significant recovery when implanted in the brain [21, 32, 33] or in the spinal cord (PEGDA-GelMA 3D printed scaffold) [34]. Few chronic‑phase studies have reported sensorimotor improvement with a brain scaffold (made of hyaluronic‑acid acrylate‑VEGF, collagen/silk fibroin, or secretome/collagen/heparan‑sulfate scaffolds) without the addition of exogenous cells [32, 33, 35]. Although this observation should be confirmed, improvements appear high in small animals such as mice but are weak in larger mammals like rats [32] or dogs [33]. Interestingly, our histological and fMRI data suggest a mechanism unrelated to direct lesion repair, but rather involving contralesional plasticity. The scaffold design, developed using CAD, demonstrated high reliability and satisfactory reproducibility. The observed swelling of the PEGDA–GelMA scaffold is a relatively constant variable across studies, ranging from 12.8 ± 3.8% to 17.0 ± 3%, depending on architecture for a given concentration; this makes it a predictable property for tissue‑engineering applications [5, 13]. 3‑D printing enables lesion‑specific structural customisation that could be extrapolated clinically to match cerebral topography. Polymerisation is adjustable, offering flexibility in the final hardness of the printed material. PEGDA–GelMA possesses an intrinsic modulus of rigidity determined by its formulation, ranging from a few kPa to several MPa. For example, when PEGDA concentration increased from 0% to 25% (v/v) in a 0.1/30% (w/v) GelMA hydrogel, the Young’s modulus rose from 0.3 to 2.9 MPa [36]. However, the porous 3‑D structure has an effective mechanical modulus assessed via compressive strength; thus, although PEGDA–GelMA belongs to a high‑stiffness range, its porosity markedly reduces overall stiffness, bringing maximum deformability down to ~ 48 ± 10 kPa—well suited to brain tissue (0.4–1.4 kPa) [37]. Longitudinal monitoring of the animals’ health revealed no long‑term adverse effects. Functional evaluation with a set of validated behavioural tests [5, 19, 20] (grip strength and neurological scale) confirmed the absence of motor or sensory deterioration associated with the scaffold during weeks and months after implantation. No major reactions were observed; functional recovery at six months surpassed spontaneous recovery in the control group (Sham scaffold), particularly for grip strength. A larger sample size and longer studies are needed to clarify inter‑group differences and better understand recovery progression. The late improvement seen after six months supports a slow, regenerative or readaptative process rather than an anti‑inflammatory one. Using 7 T MRI as a non‑invasive monitoring tool we assessed scaffold structural stability and tissue integration. The scaffold retained its architecture for up to six months. We had anticipated some long‑term degradation that would favour denser colonisation by endogenous cells. The initial porosity (53.78%) lies within the range of similar scaffolds [32], though lower than the ideally 90% recommended for neural implants [10]; it may increase progressively with biomaterial degradation, a phenomenon confirmed by imaging and histology. A porosity > 66–80% is difficult to achieve with soft 3‑D‑printed hydrogels [32, 38]. This degradation—affecting surface and mass properties [34, 39–41] promotes scaffold vacuolisation and subsequent cellular colonisation without causing premature structural loss. Notably, MRI revealed significant lesion expansion in non‑implanted animals, whereas the increase was more limited in the implanted group over six months. Ventricular hyperdilation secondary to the lesion—a frequent aggravating factor [42, 43], was reduced, indicating less secondary degeneration and a stabilising role for the scaffold in preserving cerebral architecture; as a physical barrier it may prevent deleterious tissue deformation. Despite high imaging resolution, MRI could not precisely quantify scaffold degradation kinetics because signal‑intensity variations also reflect cell colonisation and haemorrhage resorption. The specific intensities of the neo‑tissue (less hyperintense within pores compared to material) complicate direct volume interpretation. Even though a decreasing trend (~ 10 mm³ per 5 months, ≈ 19%) is observed, linear extrapolation of degradation kinetics would be unreliable. Nevertheless, once the scaffold loses mechanical cohesion, rapid fragmentation and acceleration of terminal degradation are expected [15, 41]. fMRI results showing activation at three months suggest possible reconnection between hindlimb movement and cortical activity. However, this phenomenon was observed in only two animals and did not persist at six months in one rat. We hypothesise that a more effective strategy may involve contralesional sensorimotor cortex activation by the impaired paw. Only hindlimb movement was assessed due to MRI limitations; nevertheless, these data suggest potential reconnections and raise hope for scaffold‑mediated brain regeneration. Mature neurons were not detected on histological sections—though not all sections were examined. Concurrent histology and fMRI at the same time point indicate that recovery improvement is unlikely due to new neuron formation within the scaffold; instead, it likely reflects known plasticity mechanisms involving contralesional hemisphere activation enhanced by the scaffold. Histology further revealed continuous colonisation of the scaffold for six months by Sox2⁺ pluripotent neural stem cells, which secrete trophic factors [44]. Thus, a sustained supply of growth or anti‑inflammatory factors could benefit post‑lesion brain plasticity. The most conclusive assessment of biocompatibility was based on direct brain tissue analysis. Histology showed good material tolerance: after injury a glial scar forms at the lesion periphery, acting as a physical barrier protecting surrounding healthy tissue; it may be surrounded by a fibrous capsule in strong reactions. Absence of excessive fibrosis, glial encapsulation, or heightened microglial response indicates excellent intracerebral compatibility. Barrier thickness and arrangement reflect permeability and local inflammation. Astrocytes (main glial scar component) were stained brown with GFAP/DAB. The scar was thinner than reported for other biomaterials, did not impede scaffold colonisation [19, 45–47]. Scar thinning in the PEGDA–GelMA group—from 26.6 µm to 23.7 µm between three and six months—follows an almost linear reduction trend, consistent with one‑month measurements (29.75 µm) for the same material [13]. Degradation products did not trigger secondary inflammation or alter surrounding tissues, supporting material safety. This work represents a purely endogenous regenerative approach: only the implanted biomaterial is used, without exogenous cells. The subventricular zone (SVZ) is a major source of mobilisable neural progenitors [28]; in pathological situations, it can generate ectopic migration toward injured zones, where SVZ‑derived progenitors express neuronal markers [28, 44, 48, 49]. Designing a scaffold that permits such migration and remains non‑obstructive is thus essential. The fate of SVZ progenitor cells after cortical injury remains an active research area. It is well established that following acute brain injury (e.g., stroke) most SVZ‑derived cells differentiate into astrocytes, contributing to reactive gliosis in the injured cortex [50–52]; neuronal differentiation is minimal [44]. Among the few SVZ cells adopting a neuronal fate, identity remains debated: normally they become inhibitory interneurons in the olfactory bulb [53, 54], and SVZ neuroblasts retain this identity even when redirected to the injured cortex as GABAergic interneurons [54, 55]. However, Arvidsson et al. observed SVZ‑derived cells expressing striatal dopaminergic markers, suggesting environmental influence on fate [48]. Recent studies have shown that pharmacological treatment can drive SVZ cells into mature cortical‑layer neurons [56]. Rare Dcx⁺ neuroblasts surviving to maturity form a very small population of neurons that are generally not functionally integrated into existing cortical networks; they exhibit immature morphology and limited synaptic connectivity [54]. No compelling evidence exists for SVZ progenitors generating functionally competent pyramidal cells after injury. Instead, SVZ‑derived cells likely contribute indirectly to recovery by secreting trophic factors such as VEGF, promoting neurovascular remodelling and plasticity in the peri‑lesional cortex [44]. Our results demonstrate that PEGDA–GelMA does not hinder but promotes attraction of endogenous cells. From three to six months, the lesion periphery attracted a stable or increasing Sox2⁺ and Dcx⁺ cell density in the implanted group, whereas these densities decreased in controls. This decrease may reflect parallel cell increase within the lesion, indicating migration. In the lesion without scaffold, Sox2⁺ cells remained spatially disorganised with no clear differentiation profile. On the contrary, the scaffold was colonised by Dcx⁺ cells (neuronal differentiation marker) while Sox2⁺ proportions declined, suggesting early differentiation toward functional compatibility. Although this dynamic differentiation remained relatively limited, it lasted at least over six months. It appeared earlier than in similar mouse studies, which showed marked neuronal maturation after a few months [35, 57]. TSpecies differences or intrinsic PEGDA–GelMA characteristics (rigidity, stress relaxation) may explain the limited maturation; flexible substrates (~ 700 Pa) effectively induce neuronal differentiation due to similarity with native brain tissue [58], yet development can also occur on more rigid materials [59]. Less studied but equally important, stress‑relaxation differences in biomaterials elicit distinct gene expression in neural progenitors derived from human pluripotent stem cells [60]. This study highlights the balance between PEGDA–GelMA’s excellent biocompatibility and its limited neuronal regenerative capacity. Because neurogenesis correlates strongly with angiogenesis, vascularisation is crucial for nerve regeneration; vascularisation within an exogenous 3‑D structure governs colonising tissue viability. Vascularisation within physiological norms (5–7% in healthy cortex [13]) occurs both in the scaffold and in the reconstructed lesion tissue. The scaffold’s vascular profile appears less dense than in groups without scaffolds, but access and quantification are technically challenging. In the scaffold, the vascular network colonises the entire structure by forming collaterals, rendering the new tissue viable. Additionally, the matrix is interwoven within the scaffold’s fine mesh pores. Quantitative analysis relies on well‑preserved tissue areas; autofluorescence of the biomaterial and large non‑specific immune cells trapped between patterns complicate matters. Nevertheless, colonising cells were sufficiently vascularised and nourished, enabling a viable tissue at least up to six months. Oligodendrocytes detected in this vascularised tissue may explain absence of mature neurons; Schwann cells support neuron growth whereas oligodendrocytes secrete Nogo—a powerful axonal inhibitor expressed after injury [61]. Myelin‑associated inhibitors (Nogo‑A -(reticulon-4-, MAG - myelin - associated glycoprotein-, OMgp - oligodendrocyte myelin glycoprotein-) interact with neuronal receptors (NgR1, p75/TROY, LINGO‑1), blocking axonal elongation and regeneration [62]. Blocking these inhibitors or inhibiting oligodendrocyte formation could promote neuronal maturation in the neo‑tissue. Nevertheless, oligodendrocytes secrete growth factors (BDNF, NT‑3, insulin‑like growth factor‑1) [63], making the scaffold a trophic reserve that improves plasticity. In conclusion, the 3‑D‑printed PEGDA–GelMA scaffold can be safely implanted in the brain and remains durable over the long term. Its biocompatibility supports colonisation after injury, contributing to endogenous tissue regeneration and enhanced plasticity. Low inflammatory response, preserved architecture, and gradual colonisation by differentiating progenitors and oligodendrocytes make this scaffold an encouraging option for brain regeneration without cell therapy. Finally, our results suggest that recovery benefits stem from preserving brain architecture and/or trophic factors released by endogenous colonising cells [44], rather than direct neuronal restoration. This strategy, devoid of exogenous cells, offers a smoother clinical transition, as no therapeutic cell source has yet been clinically validated. Once the intrinsic capabilities of the biomaterial are fully characterised, future studies combining PEGDA–GelMA with other extracellular‑matrix components could further enhance attraction, survival and differentiation of endogenous cells [57, 64, 65]. Declarations Ethics approval and consent to participate 'Not applicable' Consent for publication 'Not applicable' Availability of data and materials The data can be obtained from the authors upon reasonable request and with the permission of Isabelle Loubinoux. Declaration of competing interest Nothing to disclose. Funding This work was supported by Foundation “Gueules Cassées” [grant numbers 11-2023, 18-2024] [NC], Agence Innovation Défense [JC], and National Research Agency (ANR) [Grant number ANR-19-ASTR-0027]. This work, bearing the reference EUR CARe N°ANR-18-EURE-0003, has benefited from State aid managed by the Agence Nationale de la Recherche under the Programme Investissements d'Avenir. We acknowledge the support of ECELLFrance "The national research infrastructure for regenerative medicine - MSC-based therapies" (France 2030 / ANR-24-INSB-003) for the LabHPEC/Melissa Parny. Authors’ contributions MC: experimental work, data analysis and interpretation, drafting the original manuscript. VL: experimental work and data analysis. AB: MRI data analysis and interpretation, revision. JC: scaffold design and printing. LR: histological expertise. MP: histopathological experiments, revision. CC: immunofluorescence analysis and interpretation, securing funding, manuscript revision, supervision. IRL: histopathological analysis and interpretation, revision. FD: MRI acquisition, data analysis and interpretation, manuscript revision. IL: study design, data analysis and interpretation, securing funding, manuscript revision, supervision. All authors contributed to the article and approved the submitted version. Acknowledgements We thank Alexa Gouarderes and Loïc Lamadon Perié for their technical assistance; the Non-Invasive Exploration service (Carine Pestourie), Experimental Histopathology Platform and animal experiment facilities (Rachel Balouzat, Elisabeth Debon, Elsa Bodin and, Fanny Chaboud) of the US006/CREFRE-Anexplo Inserm/UT3/ENVT are gratefully acknowledged. We thank Sebastien Blanquer and Nathalia Oderich Muniz from ICGM (Institut Charles Gerhardt Montpellier) for modulus measurements. References Berthiaume, F., Maguire, T.J., Yarmush, M.L.: Tissue engineering and regenerative medicine: history, progress, and challenges. Annu Rev Chem Biomol Eng. 2, 403–430 (2011). https://doi.org/10.1146/annurev-chembioeng-061010-114257. Purvis, E.M., O’Donnell, J.C., Chen, H.I., Cullen, D.K.: Tissue Engineering and Biomaterial Strategies to Elicit Endogenous Neuronal Replacement in the Brain. Front. Neurol. 11, (2020). https://doi.org/10.3389/fneur.2020.00344. 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Exp Neurol. 235, 33–42 (2012). https://doi.org/10.1016/j.expneurol.2011.05.001. Du, Y., Dreyfus, C.F.: Oligodendrocytes as providers of growth factors. Journal of Neuroscience Research. 68, 647–654 (2002). https://doi.org/10.1002/jnr.10245. Layrolle, P., Payoux, P., Chavanas, S.: Message in a Scaffold: Natural Biomaterials for Three-Dimensional (3D) Bioprinting of Human Brain Organoids. Biomolecules. 13, 25 (2022). https://doi.org/10.3390/biom13010025. Yang, X., Qi, Y., Wang, C., Zwang, T.J., Rommelfanger, N.J., Hong, G., Lieber, C.M.: Laminin-coated electronic scaffolds with vascular topography for tracking and promoting the migration of brain cells after injury. Nature Biomedical Engineering. 7, 1282–1292 (2023). https://doi.org/10.1038/s41551-023-01101-6. Table Table 1: Immunofluorescence antibodies . Iba1: Ionized calcium-binding adapter molecule 1, Sox2: SRY-Box Transcription Factor 2, Dcx: Doublecortine, NeuN: Neuron specific Nuclear protein, Osp: Oligodendrocyte specific protein. Additional Declarations No competing interests reported. Supplementary Files VisualAbstract.pptx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 24 Feb, 2026 Editor assigned by journal 28 Jan, 2026 Submission checks completed at journal 28 Jan, 2026 First submitted to journal 27 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8711671","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":581542566,"identity":"73397624-5dc0-4740-b604-6ca5c5b56b45","order_by":0,"name":"Maylis Combeau","email":"","orcid":"","institution":"Univ Toulouse, Inserm, ToNIC","correspondingAuthor":false,"prefix":"","firstName":"Maylis","middleName":"","lastName":"Combeau","suffix":""},{"id":581542567,"identity":"222a78bb-7c95-49d6-b4cd-fcf2c48ba7ab","order_by":1,"name":"Vincent Lanternier","email":"","orcid":"","institution":"Univ Toulouse, Inserm, ToNIC","correspondingAuthor":false,"prefix":"","firstName":"Vincent","middleName":"","lastName":"Lanternier","suffix":""},{"id":581542568,"identity":"e6d9bb6a-c6d0-46b9-9b01-d57da79159b3","order_by":2,"name":"Adrien Brilhault","email":"","orcid":"","institution":"Univ Toulouse, Inserm, ToNIC","correspondingAuthor":false,"prefix":"","firstName":"Adrien","middleName":"","lastName":"Brilhault","suffix":""},{"id":581542569,"identity":"8c74b6c6-232b-46e9-84d8-753a41a7bda0","order_by":3,"name":"Julien Clauzel","email":"","orcid":"","institution":"Univ Toulouse, Inserm, ToNIC","correspondingAuthor":false,"prefix":"","firstName":"Julien","middleName":"","lastName":"Clauzel","suffix":""},{"id":581542570,"identity":"215121e4-68f5-480d-a4ce-25693dd9ee90","order_by":4,"name":"Lorenne Robert","email":"","orcid":"","institution":"Univ Toulouse, Inserm, ToNIC","correspondingAuthor":false,"prefix":"","firstName":"Lorenne","middleName":"","lastName":"Robert","suffix":""},{"id":581542571,"identity":"73efb564-64c1-4db9-aa95-4993db0b01d5","order_by":5,"name":"Nina Colitti","email":"","orcid":"","institution":"Univ Toulouse, Inserm, ToNIC","correspondingAuthor":false,"prefix":"","firstName":"Nina","middleName":"","lastName":"Colitti","suffix":""},{"id":581542572,"identity":"b77234fd-165d-4d95-93d0-77b1fbb06c46","order_by":6,"name":"Melissa Parny","email":"","orcid":"","institution":"LabHPEC, Université de Toulouse, ENVT","correspondingAuthor":false,"prefix":"","firstName":"Melissa","middleName":"","lastName":"Parny","suffix":""},{"id":581542573,"identity":"731f4ec4-1136-489b-94da-312388b3658d","order_by":7,"name":"Carla Cirillo","email":"","orcid":"","institution":"Univ Toulouse, Inserm, ToNIC","correspondingAuthor":false,"prefix":"","firstName":"Carla","middleName":"","lastName":"Cirillo","suffix":""},{"id":581542574,"identity":"dd0a9c36-c738-4c52-9750-fc84a5aae7be","order_by":8,"name":"Isabelle Raymond-Letron","email":"","orcid":"","institution":"LabHPEC, Université de Toulouse, ENVT","correspondingAuthor":false,"prefix":"","firstName":"Isabelle","middleName":"","lastName":"Raymond-Letron","suffix":""},{"id":581542575,"identity":"79820ac9-86f0-472f-9ee0-8e60db149792","order_by":9,"name":"Franck Desmoulin","email":"","orcid":"","institution":"Univ Toulouse, Inserm, ToNIC","correspondingAuthor":false,"prefix":"","firstName":"Franck","middleName":"","lastName":"Desmoulin","suffix":""},{"id":581542576,"identity":"a3314485-0680-4176-883c-9abb04dd1400","order_by":10,"name":"Isabelle Loubinoux","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFklEQVRIie3PMUvDQBTA8ScPrsvVrCeB5BMILwSiYvGztAQyBcymm4FCpopr/BaZOkceNEvdCzoEhM4VQRwCtamWCl6Lo8P9ueG4ux93B2Ay/cPcFARAcgrQAUCgdg3L8mvzoNYRsR6k2vMbIvrfBOkPZJ3cnNxBLJ7XC1IOIE7sJHl2aBa/ctL0Lo9TFAsdUdGJl5PyAUVk5zT3afpY8H0WnY1LxFxLILAlqUGKsp3woKhuC+6mTEFpsf5h1bvdkLrZEpY1y2a5Ioj678eBvfp+H7a3jIClKHcTFV95I1JehiI8z4n9o+mEuJuFFLCeuHfVuP647rlWZ/jwlDTsHM7ClzfZXFBQDbXkxwt/tR+YTCaTaU+ffoZXX0J6yzAAAAAASUVORK5CYII=","orcid":"","institution":"Univ Toulouse, Inserm, ToNIC","correspondingAuthor":true,"prefix":"","firstName":"Isabelle","middleName":"","lastName":"Loubinoux","suffix":""}],"badges":[],"createdAt":"2026-01-27 14:28:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8711671/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8711671/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101439343,"identity":"28a35dc8-4ea9-4ec9-9295-a50ede6ae7cf","added_by":"auto","created_at":"2026-01-29 16:43:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":60133,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOverview of the study protocol\u003c/strong\u003e. The time points indicated on the upper line illustrate the main experimental steps. 3D printing and scaffold decontamination (grey line) performed prior to lesion surgery; lesion surgery at D⁰, scaffold implantation at D⁺⁸; motor training/tests (MT, black line) conducted before lesion, followed by monthly motor tests thereafter. MRI was acquired at D⁰, D⁺⁸, M⁺1, M⁺3, and M⁺6. Histology was performed at M⁺3 and M⁺6.\u003c/p\u003e","description":"","filename":"Figure11.png","url":"https://assets-eu.researchsquare.com/files/rs-8711671/v1/0c62dafa9a1a9ea9c8b40408.png"},{"id":101751319,"identity":"584740ec-75a8-4984-9a33-516638396ad7","added_by":"auto","created_at":"2026-02-03 10:19:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":19616,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart of the study.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure21.png","url":"https://assets-eu.researchsquare.com/files/rs-8711671/v1/ededb086946028848d2709f5.png"},{"id":101751605,"identity":"470a5b5b-751d-43bb-a785-433ea3fce060","added_by":"auto","created_at":"2026-02-03 10:21:40","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":440810,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScaffold architecture\u003c/strong\u003e. 1: (A) Front view of the scaffold with its grip handle cut off prior to intracerebral implantation. (B) Bottom view. The flat section, without channels, corresponds to the first printed layers and is reinforced to prevent tearing. (C) Side view of the handle. (D) Cross‑section showing the 3D perspective of channels and pillars. 2: Photo of the PEGDA–GelMA scaffold (without handle) after printing on a laboratory spatula. 3: Photo of the post‑printing scaffold (without handle). Microscopic observation: photo of a scaffold stained with eosin, 20× objective under an optical microscope; (A) front view, (B) view from below.\u003c/p\u003e","description":"","filename":"Figure31.png","url":"https://assets-eu.researchsquare.com/files/rs-8711671/v1/658b207e55da2341c3c4847e.png"},{"id":101439335,"identity":"bda2d130-f234-4a64-9a42-eea5c646765d","added_by":"auto","created_at":"2026-01-29 16:43:07","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":102948,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAssessment of sensorimotor recovery after sensorimotor cortex injury using targeted behavioural tests. \u003c/strong\u003e(A) Grip strength of the forelimb contralateral to the injected hemisphere, expressed as a percentage relative to pre‑injury baseline. Lesion induced a significant decrease in forelimb strength (Wilcoxon test, p \u0026lt; 0.0001). Scaffold implantation tended to improve grip strength at six months (Mann–Whitney test, p = 0.057). (B) NSS score showing sensorimotor deficits after malonate injection (score out of 16; Wilcoxon test, p \u0026lt; 0.0001). At six months, NSS did not differ significantly between implanted and non‑implanted groups. Graphs display median values with interquartile range.\u003c/p\u003e","description":"","filename":"Figure41.png","url":"https://assets-eu.researchsquare.com/files/rs-8711671/v1/cea68f38cf3bae0d5656178e.png"},{"id":101751348,"identity":"79b42b9f-88f0-4459-a287-f67c50731c29","added_by":"auto","created_at":"2026-02-03 10:19:32","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":358530,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLongitudinal MRI monitoring.\u003c/strong\u003e (A) Representative T2-weighted MR images of rat brains implanted with a P–G scaffold (top three rows) or a sham scaffold (bottom row). Columns correspond to the four MRI time points: pre-implantation, and 1-, 3-, and 6-months post-injury. The fingerprint of the PCL cranial flap (red lines) is visible because it contains small cavities that appear hyperintense due to cerebrospinal fluid. Bregma: 0.24 mm. Scale bar: 0.5 cm. L = lesion, S = scaffold, V = ventricle. (B–D) Quantification on T2‑w scans. (B) Plot of lesion volume over time for sham‑scaffold and P‑G scaffold groups; a linear mixed model assessed time effects, with Tukey’s post hoc test (*p = 0.02, **p = 0.009). (C) Graph of scaffold volume evolution over time. (D) Graph showing scaffold intensity over time; data are normalised to contralesional cortex and shown as mean ± SD. (E) Functional MRI for two implanted rats: activation maps overlayed on T2‑w images; thresholds displayed (p \u0026lt; 0.001 or p \u0026lt; 0.01). Images show both impaired paw (warm colours) and healthy paw (cool colours) activations during passive limb mobilisation.\u003c/p\u003e","description":"","filename":"Figure51.png","url":"https://assets-eu.researchsquare.com/files/rs-8711671/v1/5f1f1477c380ea34e5801366.png"},{"id":101439339,"identity":"793bea4f-e80a-49ac-897e-6214689efc7e","added_by":"auto","created_at":"2026-01-29 16:43:07","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":664556,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFibro-collagenous reaction in injured brain tissue. \u003c/strong\u003eMasson’s trichrome staining highlights collagen fibres (blue) in response to injury. Representative sections from rats implanted with a P–G scaffold (top) or a sham scaffold (bottom) at 3 months (first panel) and 6 months (second panel). Higher magnifications illustrate interfaces: reconstructed tissue/scaffold (RT/S), healthy tissue/scaffold (HT/S), reconstructed tissue/lesion (RT/L), and healthy tissue/lesion (HT/L). Note that the biomaterial may occasionally absorb blue dye (“bubble‑like” staining), which does not indicate collagen within the material. \u003cem\u003eScale bar: whole section = 1000 µm; zoom = 50 µm.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure61.png","url":"https://assets-eu.researchsquare.com/files/rs-8711671/v1/a1473ebb90ca1b89850fa99c.png"},{"id":101439338,"identity":"42e62efd-f33a-45a5-8fb0-38bbb0fe50b6","added_by":"auto","created_at":"2026-01-29 16:43:07","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":261955,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eInflammation at the lesion periphery\u003c/strong\u003e. (A) GFAP immunohistochemistry (DAB) revealing astrocytic glial scarring at the lesion edge and/or implantation site. Yellow arrows indicate scar ‑thickness measurement locations based on GFAP density; characteristic sites are marked by black squares along lesion and implant borders. (B) Glial scar thickness in sham‑scaffold and P‑G scaffold groups at 3 and 6 months post‑lesion. Four measurements per animal; each dot represents the median value for one rat. (C) Iba1 immunofluorescence (red) highlighting microglia at lesion or implantation borders, nuclei counterstained with DAPI (blue). Black squares indicate characteristic sites for Iba1⁺ quantification. (D) Percentage of Iba1⁺ surface area (% of DAPI area) in sham‑scaffold and P‑G scaffold groups at 3 and 6 months post‑injury; each dot represents the mean of four anatomically equivalent fields per animal (mean ± SEM). \u003cem\u003eScale bar = 50 µm\u003c/em\u003e.\u003c/p\u003e","description":"","filename":"Figure71.png","url":"https://assets-eu.researchsquare.com/files/rs-8711671/v1/3d6c15ab13fadd2436ffedcd.png"},{"id":101439342,"identity":"aa95c7e3-a60f-496d-8a55-ff7345fb69f0","added_by":"auto","created_at":"2026-01-29 16:43:08","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":997544,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScaffold degradation process\u003c/strong\u003e. Hematoxylin-eosin staining (HE) of rat brain sections implanted with PEGDA-GelMA at 3 months (left panels) and 6 months (right panels). Evidence of healthy cytoarchitecture and colonising neural tissue (black arrows); biomaterial (blue arrows) appears coloured after nonspecific stain absorption, revealing its integrity. Panels from left to right: whole brain section (scale bar = 1000 µm), magnified implantation area (scale bar = 500 µm), higher magnification boxed region (scale bar = 100 µm).\u003c/p\u003e","description":"","filename":"Figure81.png","url":"https://assets-eu.researchsquare.com/files/rs-8711671/v1/565b330e50c7422b01feb353.png"},{"id":101439341,"identity":"97ed767d-d680-44e0-8cba-f18277576729","added_by":"auto","created_at":"2026-01-29 16:43:08","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":220476,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAttractiveness of the PEGDA-GelMA scaffold in a brain lesion\u003c/strong\u003e. (A-D) Quantification of the areas occupied by stem or neural progenitors cells at three locations relative to the lesion (L) at 3 and 6 months. Quantified areas: SVZ, lesion periphery (path from SVZ to lesion and around lesion), and lesion tissue (reconstruction present in sham scaffold group or within scaffold patterns for P‑G scaffold group). Locations are shown on brain sections above the graphs; representative photographs display labeling in each quantified area. Values represent mean ± SEM; dots show the mean per animal. Means are based on 4–6 quantified fields per animal, chosen to be anatomically equivalent across animals. (A) Sox2⁺ stem cells. (B) Dcx⁺ neural progenitors. (C) Lectin⁺ vasculature. (D) Osp⁺ oligodendrocytes.\u003c/p\u003e","description":"","filename":"Figure91.png","url":"https://assets-eu.researchsquare.com/files/rs-8711671/v1/a745eca79992d1ce2fc4689c.png"},{"id":101942880,"identity":"8f32337f-3e0e-4e32-b38a-e153d8efa7a0","added_by":"auto","created_at":"2026-02-05 09:39:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4012385,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8711671/v1/89f3a201-be48-4718-bc65-11159a7f7ac4.pdf"},{"id":101439336,"identity":"853ec125-fa28-4445-a388-4cc0ed7f205f","added_by":"auto","created_at":"2026-01-29 16:43:07","extension":"pptx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":874822,"visible":true,"origin":"","legend":"","description":"","filename":"VisualAbstract.pptx","url":"https://assets-eu.researchsquare.com/files/rs-8711671/v1/edf2df18654daa7a6346c75a.pptx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Dual properties of PEGDA-GelMA scaffold: Good long-term cerebral biocompatibility and motor outcome but limited potential for brain regeneration","fulltext":[{"header":"Highlights","content":"\u003cp\u003e\u0026bull; Long‑term biocompatibility of a PEGDA\u0026ndash;GelMA scaffold implanted in the injured rat brain\u003c/p\u003e\n\u003cp\u003e\u0026bull; Controlled degradation and structural stability of a PEGDA\u0026ndash;GelMA scaffold over 6 months\u003c/p\u003e\n\u003cp\u003e\u0026bull; A 3D DLP ‑printed PEGDA\u0026ndash;GelMA scaffold without cells sustains significant colonisation\u003c/p\u003e\n\u003cp\u003e\u0026bull; PEGDA\u0026ndash;GelMA scaffold enables cell colonisation and vascularisation by host cells\u003c/p\u003e\n\u003cp\u003e\u0026bull; PEGDA\u0026ndash;GelMA scaffold promotes functional recovery at 6 months post‑injury\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eRegenerative medicine aims to restore lost or impaired tissue functions by harnessing endogenous repair mechanisms and/or employing bioengineered substitutes [1]. Recent advances in bioengineering have led to the development of implantable biomaterial-based strategies capable of providing structural and bioactive support to promote cell adhesion, proliferation, migration, differentiation, and survival [2, 3]. Among these approaches, biomimetic scaffolds seek to replicate the extracellular matrix (ECM) and create a favourable environment for tissue regeneration [4]. The integration of advanced technologies, such as computer-aided design (CAD) and 3D bioprinting now enables the fabrication of complex, physiologically relevant structures with precision [5]. These constructs can not only reproduce the mechanical and biochemical properties of the ECM but also deliver cells and biomolecules in a spatially controlled manner [6, 7]. In the central nervous system, such architectures can help guide axonal regeneration by directing neurons toward their targets, thereby promoting reconnection between injured and healthy tissue [8]. To ensure optimal integration, long-term stability, and sustained functional repair, the use of biodegradable or bioeliminable materials is essential to allow complete cellular repopulation of the lesion site [9, 10].\u003c/p\u003e \u003cp\u003eNatural biomaterials offer excellent biocompatibility, biodegradability, and low cytotoxicity, but their application is hindered by insufficient mechanical strength required for implantation and tissue support [11]. In contrast, synthetic polymers provide better structural integrity but are less biocompatible and often require functionalisation with adhesion sites [12]. Thus, combining natural and synthetic polymers emerges as a promising strategy to balance biological compatibility with tunable mechanical and structural properties.\u003c/p\u003e \u003cp\u003eOur preliminary studies have demonstrated the safety and non-toxicity of intracerebral implantation of PEGDA-GelMA in the short term [5, 13]. In the brain, it showed good stability and attractiveness at 1month post-injury, without eliciting a significant inflammatory response; it was colonised by a diversified population of neural progenitor cells and exhibited proper vascularization [13]. PEGDA-GelMA is a strategic hybrid hydrogel that blends synthetic and natural components. PEGDA belongs to the category of chemical hydrogels with high stability but low biological activity and compatibility [5, 14\u0026ndash;16], while gelatin is a natural hydrogel with biomimetic relevance, essential biological components, and good cell signaling thanks to its RGD (Arginine-Glycine-Aspartic Acid) motifs [17]. To be photoprintable and acquire sufficient mechanical strength, it must be methacrylated. Together, these two biomaterials are mutually beneficial and form a promising combination for therapeutic applications in brain repair.\u003c/p\u003e \u003cp\u003eTo confirm and reinforce the potentially beneficial role of this biomaterial in brain regeneration, we set out to evaluate the biocompatibility and long-term regenerative capacity of PEGDA-GelMA in the rat brain. The resin was printed by digital light processing (DLP) into a 3D scaffold tailored to the targeted cortical anatomy. Because the degradation kinetics of PEGDA-GelMA in the brain tissue have not been described precisely, the first aim of this study was to determine its medium- and long-term stability and its degradation profile. The brain injury model validated by our group [5, 18\u0026ndash;21] involves injection of a toxin, malonate, into the motor cortex, producing significant tissue damage and functional deficits. We also investigated the intrinsic biocompatibility kinetics of PEGDA-GelMA. Subsequently, we characterized its attractiveness at 3 and 6 months paying particular attention to the neurogenic niche, cell migration to the lesion zone, and the evolution of the neo-tissue formed within the scaffold over time. Finally, functionality was assessed by behavioural motors tests and functional MRI at 3 and 6 months.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eScaffold design\u003c/p\u003e \u003cp\u003eAs in previous studies, the scaffold was designed with Autodesk Fusion 360\u0026reg; computer‑aided design software. The structural objective was threefold: to guarantee porosity, to facilitate cellular infiltration, and to guide colonisation along three orthogonal directions using horizontal channels and vertical pillars (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). We also had to ensure that the design could be inserted intracerebrally through a cranial flap with a maximum diameter of 5 mm. Lesion volumes were determined from post‑injury T2‑weighted MRI scans (see below for details).\u003c/p\u003e \u003cp\u003eThe CAD model is an adapted version of a patented brain-mimetic design [5]. While retaining its main features, the model was simplified to respect the printable resolution of PEGDA\u0026ndash;GelMA resin. It consists of two parts: i) a top handle used for manipulation, and ii) a porous scaffold with channels and pillars of varying sizes (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The handle is surgically removed during implantation.\u003c/p\u003e \u003cp\u003ePEGDA-GelMA scaffold preparation\u003c/p\u003e \u003cp\u003eScaffolds were printed on a LumenX\u0026trade; 3D printer (CellInk Inc., Sweden), which uses DLP technology at 405 nm (violet) and offers a horizontal resolution of 50 \u0026micro;m (x,y).\u003c/p\u003e \u003cp\u003eGelMA and PEGDA-200 Photo Ink\u0026trade; (CellInk Inc.) were mixed in a 1:1 ratio. After photo-crosslinking, the modulus was about 22\u0026thinsp;\u0026plusmn;\u0026thinsp;5 kPa for GelMA and 200\u0026thinsp;\u0026plusmn;\u0026thinsp;20 kPa for PEGDA-200 (CellInk Inc). Prior to mixing, each ink was individually warmed to 37\u0026deg;C. The inks are supplied ready‑to‑use and require no additional additives. Printing parameters were: layer thickness 50 \u0026micro;m, initial exposure time 15 s, subsequent exposure 5 s; light output 20 mW cm⁻\u0026sup2;; internal heating maintained at 75\u0026deg;C.\u003c/p\u003e \u003cp\u003eScaffold decontamination\u003c/p\u003e \u003cp\u003eBefore implantation, scaffolds underwent a decontamination procedure. They were rinsed three times (10 min each) with sterile Dulbecco\u0026rsquo;s phosphate‑buffered saline (PBS) and 1% penicillin\u0026ndash;streptomycin (PenStrep, Gibco). The day before implantation, scaffolds were immersed in sterile 70% ethanol for 2 h at room temperature. They were then washed three times (3x 10 minutes) with PBS containing 1% PenStrep and stored overnight at 4\u0026deg;C.\u003c/p\u003e \u003cp\u003eOn the day of implantation, scaffolds were exposed to UV light for 30 min and stored in a sealed container with the same PBS/PenStrep solution. All decontamination steps followed Biosafety Level 2 guidelines.\u003c/p\u003e \u003cp\u003eAnimals\u003c/p\u003e \u003cp\u003eSeventeen female Sprague‑Dawley rats (age 11 weeks; weight 280\u0026ndash;320 g, Janvier Labs) were pair‑housed in enriched cages (30\u0026times;18\u0026times;32 cm). They were maintained at 20\u0026deg;C on a 12‑h light/12‑h dark cycle with ad libitum food and water. All procedures complied with EU Directive 2010/63 and were approved by the Direction D\u0026eacute;partementale de la Protection des Populations de la Haute‑Garonne and the Comit\u0026eacute; d\u0026rsquo;\u0026eacute;thique pour l\u0026rsquo;exp\u0026eacute;rimentation animale Midi‑Pyr\u0026eacute;n\u0026eacute;es (protocol n\u0026deg; APAFIS#22419‑2019101115259327v5). The 3Rs principles guided the minimal use of animals, and all experiments followed ARRIVE guidelines.\u003c/p\u003e \u003cp\u003eThe distribution of rats among groups is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. At baseline: PEGDA\u0026ndash;GelMA (P‑G) scaffold group (n\u0026thinsp;=\u0026thinsp;8); Sham scaffold group (injured without implant, n\u0026thinsp;=\u0026thinsp;8); sham lesion control (not injured, n\u0026thinsp;=\u0026thinsp;1). P‑G and Sham rats received malonate‑induced brain injury. No sex differences were reported in this model [20, 21]. Half of the P‑G and Sham groups, plus the control rat, were sacrificed at 6 months; the others were sacrificed at 3 months.\u003c/p\u003e \u003cp\u003eSome Sham rats exhibited hyper‑dilated ventricles that compressed the lesion, precluding histological analysis. These animals were excluded from that assessment. Two implanted rats were also excluded: one developed a head tumour and the other had a damaged, degraded scaffold after a second surgical suturing. Consequently, final group sizes for histology were reduced: at 3 months\u0026mdash;P‑G (n\u0026thinsp;=\u0026thinsp;3), Sham (n\u0026thinsp;=\u0026thinsp;2); at 6 months\u0026mdash;P‑G (n\u0026thinsp;=\u0026thinsp;3), Sham (n\u0026thinsp;=\u0026thinsp;2), control (n\u0026thinsp;=\u0026thinsp;1). Results are presented as means\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003cp\u003eMotor function assessment\u003c/p\u003e \u003cp\u003eBehaviour was monitored throughout the study to detect clinical signs and sensorimotor recovery. Motor function was evaluated at predetermined intervals using two tests previously validated by our team [5, 19, 22]: the Grip Strength Evaluation (maximum force exerted by each forelimb) and the Neurological Severity Scale (NSS). The measurement for each paw was conducted separately. The NSS comprises five tests focused on reflexes, stability, sensitivity, and mood; scores range from 0 to 16, with higher values indicating greater deficits.\u003c/p\u003e \u003cp\u003eBrain injury induction\u003c/p\u003e \u003cp\u003eRats were anesthetised with isoflurane (3% induction, 2\u0026ndash;3% maintenance) delivered at 0.7 L min⁻\u0026sup1; O₂. They were placed in a stereotaxic frame (Bioseb lab). Pre‑medication consisted of intraperitoneal methylprednisolone (20 mg kg⁻\u0026sup1;, Centravet) and subcutaneous lidocaine (2%, 4 mg kg⁻\u0026sup1;, Centravet) for local scalp analgesia.\u003c/p\u003e \u003cp\u003eThe malonate model [19, 21] was used to induce the brain injury. One of the advantages of this technique is the ability to target key brain regions involved in human ischemic stroke, such as the sensorimotor cortex [20\u0026ndash;22]. Malonate disrupts the Krebs cycle and respiratory chain enzymes, producing a chemical energy failure that mimics ischemic excitotoxicity with a penumbra [23\u0026ndash;26]. Lesions were created by injecting 5 \u0026micro;L of a 3 M malonate solution (pH 7.4, PBS; Sigma‑Aldrich) into the motor cortex (M1) at coordinates 2.5 mm lateral and 0.5 mm anterior to Bregma, depth 2 mm [27]. The injured hemisphere corresponded to each rat\u0026rsquo;s dominant paw, as determined by grip strength. Malonate yields long‑term deficits suitable for therapeutic comparisons.\u003c/p\u003e \u003cp\u003eImplantation\u003c/p\u003e \u003cp\u003eImplantation and subsequent behavioural tests were performed blind. A second surgery was carried out on 16 rats 8 days post‑injury (peak neurogenesis [28]). Conditions matched the initial surgery. Scaffolds were inserted through a 5 mm cranial flap, removed, and repositioned at closure. Each injured rat received a wet PEGDA\u0026ndash;GelMA scaffold (PBS‑filled pores). Eight rats had their scaffolds immediately removed (Sham group); the other eight retained them for the full protocol (P‑G group). In almost all animals, a synthetic cranial flap made of PCL pellets (CellInk) replaced the bone flap. The custom flap was fabricated in a 5 mm silicone mould to secure the hole, then sealed with dental cement.\u003c/p\u003e \u003cp\u003eIn vivo MRI\u003c/p\u003e \u003cp\u003eImaging used a 7 T preclinical scanner (Biospec 70/16, Bruker). A volume transmit coil and a 2\u0026times;2 surface receiver were employed. Rats were positioned in a temperature‑regulated enclosure at 37\u0026deg;C and anaesthetised with Isoflurane/O₂ (1.5\u0026ndash;2.5% adjusted to respiration).\u003c/p\u003e \u003cp\u003eAnatomical T2 imaging used a Turbo‑RARE sequence (TE/TR\u0026thinsp;=\u0026thinsp;35.7/5452 ms), producing coronal slices; volume matrix 256\u0026times;256\u0026times;48 voxels, resolution 0.137\u0026times;0.137\u0026times;0.500 mm\u0026sup3;. Perfusion was acquired by pseudo‑continuous arterial spin labelling (pCASL) with cerebral blood flow maps (92\u0026times;92\u0026times;18 voxels, 0.326\u0026times;0.326\u0026times;0.9 mm\u0026sup3;) combined with an inversion efficiency measure [29]. Functional BOLD imaging employed an echo‑planar sequence: TE\u0026thinsp;=\u0026thinsp;11 ms, TR\u0026thinsp;=\u0026thinsp;2000 ms, FOV\u0026thinsp;=\u0026thinsp;30\u0026times;30 mm\u0026sup2;, matrix 96\u0026times;96 (resolution 313\u0026times;313 \u0026micro;m\u0026sup2;). Twenty‑one contiguous coronal slices (1 mm) were collected. Each run comprised 300 repetitions of 2 s with a block design (30 s stimulation/30 s rest); passive hindlimb stretching at 1 Hz, 2 N force was applied. Two 10-min runs per animal: contralesional first, then ipsilesional. fMRI data were analysed with SPM12 following standard preprocessing (slice‑timing, realignment, smoothing with a 0.625 mm FWHM Gaussian kernel).\u003c/p\u003e \u003cp\u003eThree anatomical scans were performed at 24 h, 1 month, and 3 months post‑lesion; rats sacrificed at 6 months underwent an additional pre‑mortem scan.\u003c/p\u003e \u003cp\u003eLesions were manually segmented on T2 images with ITKsnap: volume was calculated taking into account atrophy and dilation of ventricles, as \u003cem\u003elesion volume\u0026thinsp;+\u0026thinsp;ipsilesional ventricule \u0026ndash; contralesional ventricule\u003c/em\u003e [19].\u003c/p\u003e \u003cp\u003eHistology and immunofluorescence\u003c/p\u003e \u003cp\u003eAt 3 (n\u0026thinsp;=\u0026thinsp;8) or 6 months (n\u0026thinsp;=\u0026thinsp;9), animals received a lethal intraperitoneal injection of sodium pentobarbital (1 mL, 159 mg kg⁻\u0026sup1;, Centravet). Brain perfusion was performed with heparinised 0.9% NaCl (200 mL, 20 min) followed by 4% paraformaldehyde (250\u0026ndash;300 mL, 40 min). Brains were post‑fixed in 10% buffered formalin for 24 h at 4\u0026deg;C and embedded in paraffin. Sections (8 \u0026micro;m thick) were cut with a Leica SM 2010R microtome; ~100 coronal sections per brain were obtained.\u003c/p\u003e \u003cp\u003eEvery twelfth section was stained H\u0026amp;E and Cresyl Violet acetate. Slides were examined on a Nikon Eclipse Ci and scanned (Panoramic 3D HISTEC). Sections at the lesion site were immunostained for GFAP (1:50, clone 6F2, Invitrogen) and Masson\u0026rsquo;s trichrome, an astrocytic marker, and Masson's Trichrome (a collagen fiber marker).\u003c/p\u003e \u003cp\u003eFor immunofluorescence, sections were identified using the Paxinos\u0026ndash;Watson atlas [27]. Paraffin sections were deparaffinised, unmasked in Pt‑link low pH (K8005, Dako) for 30 min, then incubated in a humid chamber at room temperature for 30 min with a blocking buffer (1% BSA, Sigma‑Aldrich; 10% serum from donkey or goat, Thermo Fisher Scientific or Sigma-Aldrich, respectively). Primary antibodies were applied for 90 min (Table\u0026nbsp;1). After three 10‑min washes in PBS\u0026thinsp;+\u0026thinsp;0.5% BSA, secondary antibodies conjugated to fluorochromes were incubated for 50 min at room temperature in the dark. Three additional 10‑min washes followed, then a fluorescent mounting medium with DAPI (Fluoroshield\u0026trade;, Sigma‑Aldrich) was applied. Images were captured on a Nikon Eclipse Ti2 and analysed with Fiji and Imaris.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAnalyses were performed with GraphPad Prism 10. Behavioural data used non‑parametric tests; MRI data were analysed with linear mixed models. Each graph point represents one animal. Histological quantification involved 4\u0026ndash;6 fields per rat from 2\u0026ndash;3 sections. Statistical significance is indicated by asterisks, with the specific test detailed in each figure legend; non‑significant differences are marked \u0026ldquo;ns\u0026rdquo; or left unlabelled.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eScaffold technical data\u003c/p\u003e \u003cp\u003eThe architecture shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e was printed with patterns, spatial resolution and porosity suitable for tissue reconstruction. Cross‑sectional views (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e‑1D) of the CAD models allowed observation of the overall porous architecture, the organisation of interconnected layers and pillars, as well as the interior of the structures. Post‑printing photos (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e‑3AB) confirmed the porosity of the scaffolds and the removal of printing residues from pores and channels. Using an optical microscope we measured the one‑dimensional swelling of the scaffold in water; the average swelling was approximately 15.05\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8% (average 2‑D swellings of height and width, Suppl Fig.\u0026nbsp;1), comparable to previous findings with this material [5]. The average porosity was estimated at 53.78%, and the overall scaffold volume at 47.6 mm\u0026sup3; (values were computed from the 3D file and re‑adjusted with actual measurements of the printed scaffolds). It comprises a solid structure with a total volume of 22.03 mm\u0026sup3; and an empty, pore‑filled volume of 25.63 mm\u0026sup3;. Compression tests performed on nine samples determined the deformation behaviour under increasing stress; the elastic modulus was estimated at 48\u0026thinsp;\u0026plusmn;\u0026thinsp;10 kPa. This modulus renders the scaffold sufficiently rigid to support insertion into the injured brain and to withstand intracranial pressure, while also facilitating post‑impression rinses\u0026mdash;necessary to remove photochemical waste\u0026mdash;and decontamination baths prior to in vivo implantation without compromising its integrity.\u003c/p\u003e \u003cp\u003eIn vivo data\u003c/p\u003e\n\u003ch3\u003eLong-term sensorimotor improvement with PEGDA-GelMA scaffolds\u003c/h3\u003e\n\u003cp\u003eThe cortico‑striatal lesion induced a motor deficit in the contralateral paw. Grip‑strength testing provided a sensitive, quantitative measure of forelimb strength; force was expressed in newtons and normalised to pre‑lesion reference values (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). Post‑lesion performance of the contralateral forelimb showed a significant reduction (\u0026gt;\u0026thinsp;65%) in grip strength across all lesion groups (Sham scaffold: median\u0026thinsp;=\u0026thinsp;31.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.3%; P‑G scaffold: median\u0026thinsp;=\u0026thinsp;31.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6%). In the early phase after implantation, the P‑G scaffold group exhibited a recovery profile similar to spontaneous recovery in Sham animals [5, 19, 20]. From the fourth month onward, spontaneous recovery in the Sham group slowed, reaching a plateau of \u0026asymp;\u0026thinsp;59.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.9% over the four‑to‑six‑month period. Simultaneously, the P‑G scaffold curve exceeded that of the Sham group by a gain of 76.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8% at six months, yielding a trend toward significance (p\u0026thinsp;=\u0026thinsp;0.057).\u003c/p\u003e \u003cp\u003eNeurological deficits were evident, as shown by an NSS score of 12/16 (maximum deficit\u0026thinsp;=\u0026thinsp;16) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB). Both P‑G and Sham groups displayed similar spontaneous recovery over the following months, with no significant difference at six months.\u003c/p\u003e \u003cp\u003eThe sham‑injured animals (PBS injection without malonate) maintained relatively stable grip strength and NSS scores throughout the protocol, with only a slight transient decrease after control surgery.\u003c/p\u003e \u003cp\u003eThese findings suggest that P‑G scaffold implantation does not alter the early spontaneous motor recovery phase post‑brain injury; instead, therapeutic benefits on sensorimotor recovery appear to emerge in the chronic phase, beginning around month four and becoming more pronounced at six months.\u003c/p\u003e\n\u003ch3\u003eLongitudinal MRI follow-up\u003c/h3\u003e\n\u003cp\u003eAs demonstrated in our previous safety and feasibility studies, T2w MRI imaging effectively monitors implanted scaffolds over one month [5, 13]. In this study we extended the longitudinal follow‑up to six months. The high spatial resolution of MRI (137 \u0026micro;m) allowed precise observation of the implant at both macroscopic (overall scaffold morphology and perilesional environment) and microstructural levels (identification of scaffold pores).\u003c/p\u003e \u003cp\u003eWater-rich structures (PEGDA-GelMA hydrogels, damaged areas, and ventricles) appeared hyperintense on T2w images. Scaffold pores tended to be less hyperintense, healthy paranchyma regions displayed intermediate intensity, while white matter, periventricular, perilesional or peri-implant areas were hypointense (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA). These hypointensities near the implant and lesion arise from hypercellularity and may reflect migratory cells from the ventricle, thick glial scars, or collagen‑rich fibrotic tissue [5, 19]. At six months no thick hypointense rim was observed around the scaffold, suggesting an absence of dense glial scar or fibrosis.\u003c/p\u003e \u003cp\u003eIn implanted rats followed until six months, imaging revealed remarkable anatomical stability between the first and sixth months. Follow‑up images showed (i) no signs of rejection or encapsulation and (ii) preservation of scaffold shape, architecture, and porosity throughout the study period (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA). Scaffold volume matched lesion size: 51\u0026thinsp;\u0026plusmn;\u0026thinsp;28 mm\u0026sup3; at one month for sham scaffolds and 66\u0026thinsp;\u0026plusmn;\u0026thinsp;20 mm\u0026sup3; for P‑G scaffolds. Total lesion volumes (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA, first column; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB) increased significantly over time (p\u0026thinsp;\u0026lt;\u0026thinsp;0.013), with progressive dilation of the ipsilateral ventricle in the Sham group between one and three months (*p\u0026thinsp;=\u0026thinsp;0.02) and one and six months (**p\u0026thinsp;=\u0026thinsp;0.009). This expansion was less pronounced in implanted animals, indicating a stabilising role of the scaffold in local brain architecture and in preventing ventricular dilation up to the skull.\u003c/p\u003e \u003cp\u003e3D volume reconstructions from MRI scans revealed average scaffold volumes of 52.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9 mm\u0026sup3; at one month, 47.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8 mm\u0026sup3; at three months, and 42.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4 mm\u0026sup3; at six months\u0026mdash;consistent with the pre‑implantation volume (\u0026asymp;\u0026thinsp;47.6 mm\u0026sup3;) and suggesting no compression during implantation (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eC). The average decrease over months was not significant (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eC), and scaffold intensity remained unchanged, indicating temporal stability (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eD).\u003c/p\u003e \u003cp\u003eMR perfusion did not reveal cerebral blood flow within the scaffolds at three or six months; images resembled those obtained after one month [5]. Since P‑G scaffolds had not yet degraded at six months, they could not be replaced by sufficient vascularised tissue, rendering perfusion differences too subtle to detect. At three months, functional MRI showed localized activation within the scaffold in 2 of 8 implanted rats; this activation was absent at six months in one rat but a contralesional response appeared when moving the impaired limb. Perilesional activation was not observed in any animal. Frequently, movement of the paretic lower limb elicited activation in the contralesional sensorimotor cortex at the same position as for the healthy limb.\u003c/p\u003e \u003cp\u003e \u003cem\u003eEx vivo\u003c/em\u003e data\u003c/p\u003e\n\u003ch3\u003eLong-term biocompatibility\u003c/h3\u003e\n\u003cp\u003eTo assess scaffold stability and brain acceptance, we performed Masson\u0026rsquo;s trichrome staining (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e), measured glial scar thickness with GFAP immunostaining (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eA\u0026ndash;B), and quantified peri‑lesional microglia (Iba1+) (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eC\u0026ndash;D). The blue dye of Masson\u0026rsquo;s trichrome marks collagen fibres, allowing detection of fibro‑collagenous reactions after brain injury. In cases of poor biocompatibility or strong foreign ‑body reaction, a thick blue capsule may surround the implant. In our study we observed fine blue filaments within new tissue inside the scaffold and in the reconstructed tissue at the lesion edge in sham scaffolds at 3 and 6 months. These sparse collagen strands represent weak fibrosis or endogenous repair; they were unevenly distributed and did not impede tissue regeneration.\u003c/p\u003e \u003cp\u003eAt the interface between healthy host tissue and biomaterial, no collagen capsule formed after 3 or 6 months. Accumulation was more pronounced in tissues undergoing reconstruction within both sham and P‑G groups, particularly at the interface between neo‑tissue and biomaterial or between neo‑tissue and healthy tissue. A blue coloration proportional to maturity surrounded vessels supplying the damaged area; no significant inflammatory reaction exceeded that observed in one‑month safety studies [5, 13].\u003c/p\u003e \u003cp\u003eThe glial scar appeared as a dense brown layer at the lesion edge and was measured at four equivalent sites (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eA). Scar thickness at 3 and 6 months for sham and P‑G groups showed no significant differences between groups or over time, although a mild thinning trend emerged. At 3 months mean scar thickness was 23.45 \u0026micro;m (sham) and 26.67 \u0026micro;m (P‑G); at 6 months it decreased to 19.53 \u0026micro;m and 23.75 \u0026micro;m, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eB). No astrocytes were detected beyond the glial barrier within the scaffold.\u003c/p\u003e \u003cp\u003eThe implantation of the scaffold over a 6-month period did not exacerbate the inflammatory response. Microglial analysis (Iba1) revealed no differences between groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eC\u0026ndash;D); time did not alter microglial activation, and slight scaffold degradation did not increase microglia numbers.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDegradation of PEGDA-GelMA\u003c/h2\u003e \u003cp\u003eHistology confirmed MRI findings: the degradable scaffold remained intact at 3 and 6 months post‑implantation. Hematoxylin\u0026ndash;eosin staining showed stable neural cytoarchitecture and cell colonisation within the scaffolds (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e). Indirect staining of PEGDA‑GelMA by HE or Masson\u0026rsquo;s trichrome is due to gelatin\u0026rsquo;s protein motifs (amine, carboxyl) that bind dyes and to the gel\u0026rsquo;s hydrophilic, porous nature. Depending on the section, we observed pillar‑like structures (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e bottom right) or layered patterns (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e top and bottom left).\u003c/p\u003e \u003cp\u003eDye affinity allowed monitoring of degradation over time. PEGDA‑GelMA was partially altered by dehydration, embedding and sectioning, producing artefacts such as folds or distortions; nevertheless, preserved areas revealed gradual gel volume loss characterised by gaps and reduced density. A \u0026ldquo;star‑shaped\u0026rdquo; pattern emerged: a denser, purple centre fading toward the periphery, suggesting centrifugal matrix degradation. Overall scaffold structure remained intact, with localized material loss rather than complete breakdown.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAttractiveness of the PEGDA-GelMA scaffold\u003c/h3\u003e\n\u003cp\u003eBiocompatibility alone does not guarantee regenerative capacity; cellular attractiveness is also essential. We therefore assessed recruitment of neural progenitors and immature neuroblasts (Sox2\u0026thinsp;+\u0026thinsp;and Dcx+) primarily from the subventricular zone (SVZ) after implantation (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003eA\u0026ndash;B). Immunofluorescence images depict cell densities in the SVZ, lesion periphery, and core (with or without scaffold), highlighting endogenous repair.\u003c/p\u003e \u003cp\u003eIn the SVZ, time seemed to favor the production of immature neuroblasts. Sox2\u0026thinsp;+\u0026thinsp;density decreased between 3 and 6 months in both groups (sham: 53%\u0026rarr;34%; P‑G: 46%\u0026rarr;41%), whereas Dcx+ remained stable or increased slightly (sham: 21%\u0026rarr;22%; P‑G: 14%\u0026rarr;22%). At the lesion periphery, Sox2\u0026thinsp;+\u0026thinsp;and Dcx+ densities declined over time in sham animals but stayed stable in the P‑G group (sham: Sox2\u0026thinsp;+\u0026thinsp;35%\u0026rarr;29%; Dcx\u0026thinsp;+\u0026thinsp;5%\u0026rarr;4%; P‑G: Sox2\u0026thinsp;+\u0026thinsp;35%\u0026rarr;35%; Dcx\u0026thinsp;+\u0026thinsp;5%\u0026rarr;6%). Thus, peripheral attractiveness was better preserved with the P‑G scaffold.\u003c/p\u003e \u003cp\u003eWithin the lesion core, sham animals showed increased new cell populations over time (Sox2\u0026thinsp;+\u0026thinsp;14%\u0026rarr;25%; Dcx\u0026thinsp;+\u0026thinsp;0%\u0026rarr;2%). In contrast, the P‑G group displayed a decrease in Sox2\u0026thinsp;+\u0026thinsp;cells (25%\u0026rarr;12%) and an increase in Dcx+ cells (2%\u0026rarr;5%).\u003c/p\u003e \u003cp\u003eNeuronal maturation was evaluated with β‑III tubulin (immature) and NeuN (mature). β‑III tubulin+ neurons were present but unevenly distributed; no NeuN+ cells were detected in reconstructed tissue for either group.\u003c/p\u003e \u003cp\u003eVascularisation, a key determinant of cell survival in issue undergoing reconstruction, was quantified using lectin staining, an endothelial marker. Both groups exhibited increased vascular density from 3 to 6 months (sham: 5%\u0026rarr;8%; P‑G: 5%\u0026rarr;6%).\u003c/p\u003e \u003cp\u003eOligodendrocyte numbers were assessed with the OSP(oligodendrocyte-specific protein) marker, a membrane marker of tight junctions. The P‑G scaffold group maintained higher oligodendrocyte densities, which remained stable between 3 and 6 months (sham: 3%\u0026rarr;4%; P‑G: 5%\u0026rarr;10%).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this \u003cem\u003ein‑vivo\u003c/em\u003e study we describe the behaviour of a 3‑D PEGDA\u0026ndash;GelMA scaffold implanted in an injured rat brain and followed longitudinally for up to 3 and 6 months. The work covers all stages of the project\u0026mdash;from design and manufacture to non‑invasive \u003cem\u003ein‑vivo\u003c/em\u003e evaluation and post‑mortem histological characterisation. Through dual‑kinetic monitoring we aimed to extract gradual data concerning the long‑term degradation of PEGDA\u0026ndash;GelMA in brain tissue, which is currently unknown. Long‑term assessments are particularly relevant for studying chronic inflammation associated with biomaterials\u0026mdash;especially in the CNS\u0026mdash;and for evaluating their regenerative or scarring impact in an \u003cem\u003ein‑vivo\u003c/em\u003e context [30, 31]. We demonstrated preservation of scaffold architecture over six months and a beginning of degradation. Our results show a trend toward improved grip strength. Generally, only scaffolds bearing cells or cellular secretome achieve significant recovery when implanted in the brain [21, 32, 33] or in the spinal cord (PEGDA-GelMA 3D printed scaffold) [34]. Few chronic‑phase studies have reported sensorimotor improvement with a brain scaffold (made of hyaluronic‑acid acrylate‑VEGF, collagen/silk fibroin, or secretome/collagen/heparan‑sulfate scaffolds) without the addition of exogenous cells [32, 33, 35]. Although this observation should be confirmed, improvements appear high in small animals such as mice but are weak in larger mammals like rats [32] or dogs [33]. Interestingly, our histological and fMRI data suggest a mechanism unrelated to direct lesion repair, but rather involving contralesional plasticity.\u003c/p\u003e \u003cp\u003eThe scaffold design, developed using CAD, demonstrated high reliability and satisfactory reproducibility. The observed swelling of the PEGDA\u0026ndash;GelMA scaffold is a relatively constant variable across studies, ranging from 12.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8% to 17.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3%, depending on architecture for a given concentration; this makes it a predictable property for tissue‑engineering applications [5, 13]. 3‑D printing enables lesion‑specific structural customisation that could be extrapolated clinically to match cerebral topography. Polymerisation is adjustable, offering flexibility in the final hardness of the printed material. PEGDA\u0026ndash;GelMA possesses an intrinsic modulus of rigidity determined by its formulation, ranging from a few kPa to several MPa. For example, when PEGDA concentration increased from 0% to 25% (v/v) in a 0.1/30% (w/v) GelMA hydrogel, the Young\u0026rsquo;s modulus rose from 0.3 to 2.9 MPa [36]. However, the porous 3‑D structure has an effective mechanical modulus assessed via compressive strength; thus, although PEGDA\u0026ndash;GelMA belongs to a high‑stiffness range, its porosity markedly reduces overall stiffness, bringing maximum deformability down to ~\u0026thinsp;48\u0026thinsp;\u0026plusmn;\u0026thinsp;10 kPa\u0026mdash;well suited to brain tissue (0.4\u0026ndash;1.4 kPa) [37].\u003c/p\u003e \u003cp\u003eLongitudinal monitoring of the animals\u0026rsquo; health revealed no long‑term adverse effects. Functional evaluation with a set of validated behavioural tests [5, 19, 20] (grip strength and neurological scale) confirmed the absence of motor or sensory deterioration associated with the scaffold during weeks and months after implantation. No major reactions were observed; functional recovery at six months surpassed spontaneous recovery in the control group (Sham scaffold), particularly for grip strength. A larger sample size and longer studies are needed to clarify inter‑group differences and better understand recovery progression. The late improvement seen after six months supports a slow, regenerative or readaptative process rather than an anti‑inflammatory one.\u003c/p\u003e \u003cp\u003eUsing 7 T MRI as a non‑invasive monitoring tool we assessed scaffold structural stability and tissue integration. The scaffold retained its architecture for up to six months. We had anticipated some long‑term degradation that would favour denser colonisation by endogenous cells. The initial porosity (53.78%) lies within the range of similar scaffolds [32], though lower than the ideally 90% recommended for neural implants [10]; it may increase progressively with biomaterial degradation, a phenomenon confirmed by imaging and histology. A porosity\u0026thinsp;\u0026gt;\u0026thinsp;66\u0026ndash;80% is difficult to achieve with soft 3‑D‑printed hydrogels [32, 38]. This degradation\u0026mdash;affecting surface and mass properties [34, 39\u0026ndash;41] promotes scaffold vacuolisation and subsequent cellular colonisation without causing premature structural loss.\u003c/p\u003e \u003cp\u003eNotably, MRI revealed significant lesion expansion in non‑implanted animals, whereas the increase was more limited in the implanted group over six months. Ventricular hyperdilation secondary to the lesion\u0026mdash;a frequent aggravating factor [42, 43], was reduced, indicating less secondary degeneration and a stabilising role for the scaffold in preserving cerebral architecture; as a physical barrier it may prevent deleterious tissue deformation.\u003c/p\u003e \u003cp\u003eDespite high imaging resolution, MRI could not precisely quantify scaffold degradation kinetics because signal‑intensity variations also reflect cell colonisation and haemorrhage resorption. The specific intensities of the neo‑tissue (less hyperintense within pores compared to material) complicate direct volume interpretation. Even though a decreasing trend (~\u0026thinsp;10 mm\u0026sup3; per 5 months, \u0026asymp;\u0026thinsp;19%) is observed, linear extrapolation of degradation kinetics would be unreliable. Nevertheless, once the scaffold loses mechanical cohesion, rapid fragmentation and acceleration of terminal degradation are expected [15, 41].\u003c/p\u003e \u003cp\u003efMRI results showing activation at three months suggest possible reconnection between hindlimb movement and cortical activity. However, this phenomenon was observed in only two animals and did not persist at six months in one rat. We hypothesise that a more effective strategy may involve contralesional sensorimotor cortex activation by the impaired paw. Only hindlimb movement was assessed due to MRI limitations; nevertheless, these data suggest potential reconnections and raise hope for scaffold‑mediated brain regeneration. Mature neurons were not detected on histological sections\u0026mdash;though not all sections were examined. Concurrent histology and fMRI at the same time point indicate that recovery improvement is unlikely due to new neuron formation within the scaffold; instead, it likely reflects known plasticity mechanisms involving contralesional hemisphere activation enhanced by the scaffold. Histology further revealed continuous colonisation of the scaffold for six months by Sox2⁺ pluripotent neural stem cells, which secrete trophic factors [44]. Thus, a sustained supply of growth or anti‑inflammatory factors could benefit post‑lesion brain plasticity.\u003c/p\u003e \u003cp\u003eThe most conclusive assessment of biocompatibility was based on direct brain tissue analysis. Histology showed good material tolerance: after injury a glial scar forms at the lesion periphery, acting as a physical barrier protecting surrounding healthy tissue; it may be surrounded by a fibrous capsule in strong reactions. Absence of excessive fibrosis, glial encapsulation, or heightened microglial response indicates excellent intracerebral compatibility. Barrier thickness and arrangement reflect permeability and local inflammation. Astrocytes (main glial scar component) were stained brown with GFAP/DAB. The scar was thinner than reported for other biomaterials, did not impede scaffold colonisation [19, 45\u0026ndash;47]. Scar thinning in the PEGDA\u0026ndash;GelMA group\u0026mdash;from 26.6 \u0026micro;m to 23.7 \u0026micro;m between three and six months\u0026mdash;follows an almost linear reduction trend, consistent with one‑month measurements (29.75 \u0026micro;m) for the same material [13]. Degradation products did not trigger secondary inflammation or alter surrounding tissues, supporting material safety.\u003c/p\u003e \u003cp\u003eThis work represents a purely endogenous regenerative approach: only the implanted biomaterial is used, without exogenous cells. The subventricular zone (SVZ) is a major source of mobilisable neural progenitors [28]; in pathological situations, it can generate ectopic migration toward injured zones, where SVZ‑derived progenitors express neuronal markers [28, 44, 48, 49]. Designing a scaffold that permits such migration and remains non‑obstructive is thus essential.\u003c/p\u003e \u003cp\u003eThe fate of SVZ progenitor cells after cortical injury remains an active research area. It is well established that following acute brain injury (e.g., stroke) most SVZ‑derived cells differentiate into astrocytes, contributing to reactive gliosis in the injured cortex [50\u0026ndash;52]; neuronal differentiation is minimal [44]. Among the few SVZ cells adopting a neuronal fate, identity remains debated: normally they become inhibitory interneurons in the olfactory bulb [53, 54], and SVZ neuroblasts retain this identity even when redirected to the injured cortex as GABAergic interneurons [54, 55]. However, Arvidsson et al. observed SVZ‑derived cells expressing striatal dopaminergic markers, suggesting environmental influence on fate [48]. Recent studies have shown that pharmacological treatment can drive SVZ cells into mature cortical‑layer neurons [56]. Rare Dcx⁺ neuroblasts surviving to maturity form a very small population of neurons that are generally not functionally integrated into existing cortical networks; they exhibit immature morphology and limited synaptic connectivity [54]. No compelling evidence exists for SVZ progenitors generating functionally competent pyramidal cells after injury. Instead, SVZ‑derived cells likely contribute indirectly to recovery by secreting trophic factors such as VEGF, promoting neurovascular remodelling and plasticity in the peri‑lesional cortex [44].\u003c/p\u003e \u003cp\u003eOur results demonstrate that PEGDA\u0026ndash;GelMA does not hinder but promotes attraction of endogenous cells. From three to six months, the lesion periphery attracted a stable or increasing Sox2⁺ and Dcx⁺ cell density in the implanted group, whereas these densities decreased in controls. This decrease may reflect parallel cell increase within the lesion, indicating migration. In the lesion without scaffold, Sox2⁺ cells remained spatially disorganised with no clear differentiation profile. On the contrary, the scaffold was colonised by Dcx⁺ cells (neuronal differentiation marker) while Sox2⁺ proportions declined, suggesting early differentiation toward functional compatibility. Although this dynamic differentiation remained relatively limited, it lasted at least over six months. It appeared earlier than in similar mouse studies, which showed marked neuronal maturation after a few months [35, 57]. TSpecies differences or intrinsic PEGDA\u0026ndash;GelMA characteristics (rigidity, stress relaxation) may explain the limited maturation; flexible substrates (~\u0026thinsp;700 Pa) effectively induce neuronal differentiation due to similarity with native brain tissue [58], yet development can also occur on more rigid materials [59]. Less studied but equally important, stress‑relaxation differences in biomaterials elicit distinct gene expression in neural progenitors derived from human pluripotent stem cells [60].\u003c/p\u003e \u003cp\u003eThis study highlights the balance between PEGDA\u0026ndash;GelMA\u0026rsquo;s excellent biocompatibility and its limited neuronal regenerative capacity. Because neurogenesis correlates strongly with angiogenesis, vascularisation is crucial for nerve regeneration; vascularisation within an exogenous 3‑D structure governs colonising tissue viability. Vascularisation within physiological norms (5\u0026ndash;7% in healthy cortex [13]) occurs both in the scaffold and in the reconstructed lesion tissue. The scaffold\u0026rsquo;s vascular profile appears less dense than in groups without scaffolds, but access and quantification are technically challenging. In the scaffold, the vascular network colonises the entire structure by forming collaterals, rendering the new tissue viable. Additionally, the matrix is interwoven within the scaffold\u0026rsquo;s fine mesh pores. Quantitative analysis relies on well‑preserved tissue areas; autofluorescence of the biomaterial and large non‑specific immune cells trapped between patterns complicate matters. Nevertheless, colonising cells were sufficiently vascularised and nourished, enabling a viable tissue at least up to six months. Oligodendrocytes detected in this vascularised tissue may explain absence of mature neurons; Schwann cells support neuron growth whereas oligodendrocytes secrete Nogo\u0026mdash;a powerful axonal inhibitor expressed after injury [61]. Myelin‑associated inhibitors (Nogo‑A -(reticulon-4-, MAG - myelin\u003cem\u003e-\u003c/em\u003eassociated glycoprotein-, OMgp - oligodendrocyte myelin glycoprotein-) interact with neuronal receptors (NgR1, p75/TROY, LINGO‑1), blocking axonal elongation and regeneration [62]. Blocking these inhibitors or inhibiting oligodendrocyte formation could promote neuronal maturation in the neo‑tissue. Nevertheless, oligodendrocytes secrete growth factors (BDNF, NT‑3, insulin‑like growth factor‑1) [63], making the scaffold a trophic reserve that improves plasticity.\u003c/p\u003e \u003cp\u003eIn conclusion, the 3‑D‑printed PEGDA\u0026ndash;GelMA scaffold can be safely implanted in the brain and remains durable over the long term. Its biocompatibility supports colonisation after injury, contributing to endogenous tissue regeneration and enhanced plasticity. Low inflammatory response, preserved architecture, and gradual colonisation by differentiating progenitors and oligodendrocytes make this scaffold an encouraging option for brain regeneration without cell therapy. Finally, our results suggest that recovery benefits stem from preserving brain architecture and/or trophic factors released by endogenous colonising cells [44], rather than direct neuronal restoration.\u003c/p\u003e \u003cp\u003eThis strategy, devoid of exogenous cells, offers a smoother clinical transition, as no therapeutic cell source has yet been clinically validated. Once the intrinsic capabilities of the biomaterial are fully characterised, future studies combining PEGDA\u0026ndash;GelMA with other extracellular‑matrix components could further enhance attraction, survival and differentiation of endogenous cells [57, 64, 65].\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026apos;Not applicable\u0026apos;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026apos;Not applicable\u0026apos;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data can be obtained from the authors upon reasonable request and with the permission of Isabelle Loubinoux.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of competing interest \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNothing to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Foundation \u0026ldquo;Gueules Cass\u0026eacute;es\u0026rdquo; [grant numbers 11-2023, 18-2024] [NC], Agence Innovation D\u0026eacute;fense [JC], and National Research Agency (ANR) [Grant number ANR-19-ASTR-0027]. This work, bearing the reference EUR CARe N\u0026deg;ANR-18-EURE-0003, has benefited from State aid managed by the Agence Nationale de la Recherche under the Programme Investissements d\u0026apos;Avenir. We acknowledge the support of ECELLFrance \u0026quot;The national research infrastructure for regenerative medicine - MSC-based therapies\u0026quot; (France 2030 / ANR-24-INSB-003) for the LabHPEC/Melissa Parny. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMC: experimental work, data analysis and interpretation, drafting the original manuscript. VL: experimental work and data analysis. AB: MRI data analysis and interpretation, revision. \u0026nbsp;JC: scaffold design and printing. LR: histological expertise. MP: histopathological experiments, revision. CC: immunofluorescence analysis and interpretation, securing funding, manuscript revision, supervision. IRL: histopathological analysis and interpretation, revision. FD: MRI acquisition, data analysis and interpretation, manuscript revision. IL: study design, data analysis and interpretation, securing funding, manuscript revision, supervision. All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Alexa Gouarderes and Lo\u0026iuml;c Lamadon Peri\u0026eacute; for their technical assistance; the Non-Invasive Exploration service (Carine Pestourie), Experimental Histopathology Platform and animal experiment facilities (Rachel Balouzat, Elisabeth Debon, Elsa Bodin and, Fanny Chaboud) of the US006/CREFRE-Anexplo Inserm/UT3/ENVT are gratefully acknowledged. We thank Sebastien Blanquer and Nathalia Oderich Muniz from ICGM (Institut Charles Gerhardt Montpellier) for modulus measurements. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBerthiaume, F., Maguire, T.J., Yarmush, M.L.: Tissue engineering and regenerative medicine: history, progress, and challenges. Annu Rev Chem Biomol Eng. 2, 403\u0026ndash;430 (2011). https://doi.org/10.1146/annurev-chembioeng-061010-114257.\u003c/li\u003e\n\u003cli\u003ePurvis, E.M., O\u0026rsquo;Donnell, J.C., Chen, H.I., Cullen, D.K.: Tissue Engineering and Biomaterial Strategies to Elicit Endogenous Neuronal Replacement in the Brain. Front. Neurol. 11, (2020). https://doi.org/10.3389/fneur.2020.00344.\u003c/li\u003e\n\u003cli\u003eTuladhar, A., Payne, S.L., Shoichet, M.S.: Harnessing the Potential of Biomaterials for Brain Repair after Stroke. Front. 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J Funct Biomater. 14, 96 (2023). https://doi.org/10.3390/jfb14020096.\u003c/li\u003e\n\u003cli\u003eYue, K., Santiago, G.T., Alvarez, M.M., Tamayol, A., Annabi, N., Khademhosseini, A.: Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 73, 254\u0026ndash;271 (2015). https://doi.org/10.1016/j.biomaterials.2015.08.045.\u003c/li\u003e\n\u003cli\u003eCirillo, C., Le Friec, A., Frisach, I., Darmana, R., Robert, L., Desmoulin, F., Loubinoux, I.: Focal Malonate Injection Into the Internal Capsule of Rats as a Model of Lacunar Stroke. Front Neurol. 9, 1072 (2018). https://doi.org/10.3389/fneur.2018.01072.\u003c/li\u003e\n\u003cli\u003eColitti, N., Desmoulin, F., Le Friec, A., Labriji, W., Robert, L., Michaux, A., Conchou, F., Cirillo, C., Loubinoux, I.: Long-Term Intranasal Nerve Growth Factor Treatment Favors Neuron Formation in de novo Brain Tissue. Front. Cell. 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Nature Biomedical Engineering. 7, 1282\u0026ndash;1292 (2023). https://doi.org/10.1038/s41551-023-01101-6.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1: \u003cstrong\u003eImmunofluorescence antibodies\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cimg 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width=\"695\" height=\"322\"\u003e\u003c/p\u003e\n\u003cp\u003eIba1: Ionized calcium-binding adapter molecule 1, Sox2: SRY-Box Transcription Factor 2, Dcx: Doublecortine, NeuN: Neuron specific Nuclear protein, Osp: Oligodendrocyte specific protein.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"stem-cell-research-and-therapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scrt","sideBox":"Learn more about [Stem Cell Research \u0026 Therapy](http://stemcellres.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/scrt/default.aspx","title":"Stem Cell Research \u0026 Therapy","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"3D DLP printing, PEGDA, GelMA, Tissue bioengineering, Acute brain injury, MRI, Behaviour, Brain repair","lastPublishedDoi":"10.21203/rs.3.rs-8711671/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8711671/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBACKGROUND\u003c/h2\u003e \u003cp\u003eAcute brain injuries represent a major clinical challenge, as current therapeutic strategies are insufficient to promote tissue regeneration and fully restore lost neurological functions. In this context, biomaterials have shown promise in promoting tissue repair.\u003c/p\u003e\u003ch2\u003eMETHODS\u003c/h2\u003e \u003cp\u003eThis study introduces an innovative strategy involving the 3D DLP (Digital Light Processing) printing of a degradable scaffold composed of PEGDA (polyethylene ‑glycol diacrylate) and GelMA (gelatin methacryloyl). The neuro‑implant combines the mechanical stability of PEGDA with the bioactivity and biocompatibility of gelatin, forming a porous and guiding architecture. This scaffold is implanted in rat brains injured by malonate injection.\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e \u003cp\u003eDLP technology enabled the complex scaffold architecture specific to the cortex. A longitudinal follow‑up using behavioural assays and MR imaging at 3‑ and 6‑months post‑injury revealed a favourable in ‑vivo safety profile, contralesional functional MR activation, and improved grip strength of the impaired forelimb at 6 months (p\u0026thinsp;=\u0026thinsp;0.057). MRI provided high‑quality images revealing the scaffold\u0026rsquo;s fine architecture in vivo and showed no degradation. Histological analysis confirmed chronic biocompatibility, with complete colonisation by viable endogenous cells, including a stable vascular network persisting at 6 months and a high density of neural progenitors (Sox2⁺, Dcx⁺) and mature oligodendrocytes (OSP⁺), offset by a surprising absence of mature, functional neurons and astrocytes.\u003c/p\u003e\u003ch2\u003eCONCLUSION\u003c/h2\u003e \u003cp\u003eOur results highlight the long‑term biocompatibility of the PEGDA\u0026ndash;GelMA scaffold in the brain, but its functional regenerative potential is limited. Nevertheless, this implant appears capable of improving functional motor outcome; this improvement was not explained by neuron or astrocyte attraction. PEGDA\u0026ndash;GelMA can serve as a structural bridge between healthy and damaged brain tissue, attracting endogenous cells. The implant stabilises the lesion site and may enhance brain plasticity mechanisms such as contralesional motor ‑cortex involvement. These findings provide an acellular basis for developing a regenerative, brain‑compatible structural platform targeting central nervous system lesions.\u003c/p\u003e","manuscriptTitle":"Dual properties of PEGDA-GelMA scaffold: Good long-term cerebral biocompatibility and motor outcome but limited potential for brain regeneration","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-29 16:43:02","doi":"10.21203/rs.3.rs-8711671/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-24T15:45:12+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-28T05:49:23+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-28T05:47:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"Stem Cell Research \u0026 Therapy","date":"2026-01-27T14:00:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"stem-cell-research-and-therapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scrt","sideBox":"Learn more about [Stem Cell Research \u0026 Therapy](http://stemcellres.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/scrt/default.aspx","title":"Stem Cell Research \u0026 Therapy","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"aeaf20c8-6b3d-4d78-a9d6-151ea49f7953","owner":[],"postedDate":"January 29th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-10T07:53:57+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-29 16:43:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8711671","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8711671","identity":"rs-8711671","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}