Extrusion-based 3D Printing of PEG400-Plasticized HA/PCL Composite Scaffolds: A Study on Flexible Adaptation for Eyelid Defect Repair

Extrusion-based 3D Printing of PEG400-Plasticized HA/PCL Composite Scaffolds: A Study on Flexible Adaptation for Eyelid Defect Repair | 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 Article Extrusion-based 3D Printing of PEG400-Plasticized HA/PCL Composite Scaffolds: A Study on Flexible Adaptation for Eyelid Defect Repair Jincheng Liu, Simeng Lv, Mengling Zhou, Mange Zhang, Qingyi Wang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7969055/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose This study developed extrusion-based 3D-printed PEG400-plasticized HA/PCL composite scaffolds for posterior lamellar eyelid reconstruction, optimizing material ratios to match native tarsal tissue properties. Methods Two scaffolds (70% vs 84% HA) were fabricated via pneumatic extrusion. Microstructure (SEM), porosity (Micro-CT), wettability (contact angle), and mechanical properties (tensile testing) were characterized. Statistical analysis used GraphPad Prism 8. Results The 84% HA scaffold achieved an elastic modulus of ​2.66 MPa, closely aligning with native tarsal tissue (1.73 ± 0.61 MPa). Hierarchical pores (macropores: ~570.7 µm; micropores: ~20.81 µm) and high porosity (91.66%​) were observed. Both scaffolds showed hydrophilicity (contact angles: ​80.63°​ for 70% HA; ​77.97°​ for 84% HA). Though the 84% HA group had lower tensile strength, its biomechanical compatibility surpassed the 70% HA scaffold. Conclusion The 84% HA/PCL scaffold exhibits optimal mechanical adaptation, porous architecture, and hydrophilicity for eyelid tarsal reconstruction. Its slow degradation profile supports clinical potential, pending in vitro cytocompatibility and in vivo validation. Biological sciences/Biotechnology Physical sciences/Engineering Physical sciences/Materials science Health sciences/Medical research Eyelid reconstruction 3D printing Hydroxyapatite Polycaprolactone Biomechanical compatibility Tissue engineering Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1 Introduction The eyelid is a crucial structure for maintaining ocular health and facial aesthetics, with physiological functions encompassing three key dimensions: protecting the eyeball from external damage, maintaining a moist ocular surface environment to ensure transparency of optical media, and participating in the formation of dynamic facial expressions [ 1 , 2 ] . Anatomically [ 3 – 5 ] , the eyelid consists of an anterior skin-muscle layer and a posterior tarsoconjunctival layer, forming a precise functional complex. The anterior layer includes the skin and orbicularis oculi muscle, responsible for blink function and shaping the external contour; the posterior layer is composed of the tarsus and palpebral conjunctiva, providing core mechanical support and ocular surface lubrication. This anatomical layering specificity dictates that reconstruction surgery must strictly adhere to the "Like for like" principle [ 1 , 6 , 7 ] , meaning substitute materials must highly match the original state of the defective tissue in both structural characteristics and biological function. Therefore, the repair of posterior lamellar eyelid defects constitutes a core challenge in clinical treatment. Hydroxyapatite (HA) is the main inorganic component of human bone (50–70%). Its hexagonal crystal system structure (space group P6 3 /m) shares chemical and crystallographic homology with natural bone mineral, forming the basis of its biological function. The Ca 2+ , PO 4 3− , and OH − ions in its chemical formula Ca 10 (PO 4 ) 6 (OH) 2 are all endogenous, avoiding implantation toxicity [ 8 ] . HA particles, due to their high specific surface area and biomimetic mineral characteristics, enhance surface and interface effects, demonstrating superior cell adhesion, proliferation, and differentiation regulation capabilities compared to ordinary HA, which is crucial for bone regeneration [ 9 ] . HA, as a brittle polycrystalline material, has mechanical properties (strength, toughness, etc.) comprehensively influenced by factors such as grain size, crystallinity, grain boundary state, chemical composition, and porosity [ 10 ] . Its brittleness originates from its strong ionic bond structure, leading to poor plastic deformation ability and sensitivity to microcracks, making it prone to fracture under load. Processes like sintering can reduce grain size to improve strength and toughness, as fine-grained structures have fewer grain boundary defects [ 11 ] . High crystallinity and low porosity can enhance stiffness, tensile/compressive strength, and fracture toughness; conversely, amorphous phases or porous structures weaken mechanical performance [ 9 ] . In bone repair, the success of HA composites relies on mechanical adaptability and promoting angiogenesis. Strength can be improved by introducing organic polymers (e.g., collagen, polylactic acid) or inorganic reinforcing phases (e.g., bioactive glass, calcium phosphate) [ 12 ] . Therefore, inorganic/organic composite materials show significant application potential due to their adjustable tissue adaptability and functional designability. Early preparation methods involving direct mixing of HA and polymers suffered from issues like uneven phase distribution and weak interfacial bonding, but advanced techniques (e.g., in-situ deposition, freeze-drying, 3D printing) have effectively broken through this bottleneck [ 13 , 14 ] . HA has good biocompatibility, promoting cell attachment, growth, and differentiation [ 15 ] . Compositing with collagen, polylactic acid, etc., can further enhance biocompatibility and mechanical properties, promoting osseointegration [ 16 ] . Its applications have expanded to drug delivery, biosensing, and regenerative medicine [ 17 ] . By controlling synthesis conditions (e.g., pH, temperature), its microstructure and properties can be precisely optimized, and fiber composite strategies can also improve the brittleness of traditional HA-based scaffolds. Polycaprolactone (PCL) is a synthetic aliphatic polyester with excellent mechanical properties, controlled degradability, and biocompatibility, making it widely used in tissue engineering [ 18 ] . Its tensile modulus (343.9-363.4 MPa) and compressive strength (216 MPa) are comparable to those of natural bone, making it suitable for bone and cartilage regeneration. Its degradation cycle exceeds two years, and its degradation products are non-toxic, having been approved by the FDA for use in implants and scaffolds [ 19 – 21 ] . However, PCL's inherent hydrophobicity hinders cell adhesion, often necessitating surface modification (e.g., plasma treatment or hydrophilic coating) to enhance bioactivity [ 22 ] . In regard to the processing stage, the thermoplasticity and melt stability of PCLs serve to facilitate the implementation of a variety of advanced manufacturing technologies. Three-dimensional printing (e.g., fused deposition modeling) has the capacity to construct high-precision microstructural scaffolds that are suitable for bone defect repair [ 23 ] . Electrospinning can produce nanofibers (diameter 75–344 nm) to promote cell infiltration [ 24 ] . Furthermore, particle impregnation has the potential to produce high-porosity (85–88%) foam scaffolds that can provide mechanical support for soft tissues [ 25 ] . In the domain of tissue engineering, PCL scaffolds exhibit a wide range of applications. In the field of dermatology, PCL electrospun membranes have been shown to mimic the extracellular matrix (ECM). These membranes exhibit high porosity (> 90%) and hydrophilic modification, which has been demonstrated to promote keratinocyte proliferation and wound healing [ 26 , 27 ] . In the field of bone regeneration, PCL scaffolds loaded with drugs, such as metformin, have been shown to promote osteoblast differentiation and mineralization. The integration of 3D printing technology allows for the fabrication of customized pore structures, which can be tailored to specific biological requirements [ 28 – 30 ] . In the domain of vascular engineering, PCL-based grafts, including small-diameter vessels, when combined with heparin coating, have demonstrated the capacity to enhance anticoagulant properties and endothelial growth. These grafts exhibit mechanical properties that satisfy the physiological pressure requirements of the vasculature [ 31 , 32 ] . In the context of neural repair, PCL nanofiber scaffolds have been observed to improve Schwann cell adhesion by reducing fiber diameter. 180 nm), and gold nanoparticle doping has been demonstrated to facilitate conductivity, thereby promoting axon regeneration [ 33 , 34 ] . Current PCL research focuses on functionalization and intelligent design: drug delivery systems utilize PCL nanoparticles to load anticancer drugs and improve targeting through surface modification [ 35 ] ; 4D printing combined with shape memory PCL can construct dynamically responsive scaffolds (e.g., simulating lung expansion) for respiratory tissue engineering [ 36 ] ; emerging directions include mussel protein functionalization to enhance osseointegration [ 37 ] , and developing conductive composite materials for neural regulation [ 38 ] , promoting the development of personalized medicine. These advances indicate that PCL is evolving from a traditional scaffold to a multifunctional therapeutic platform. Given the adjustable mechanical properties and structural freedom of synthetic polymer composites, this study proposes a composite scaffold system based on polycaprolactone/hydroxyapatite (PCL/HA), constructing a porous structure through pneumatic extrusion technology and introducing polyethylene glycol (PEG) to regulate material toughness. The elastic modulus and tensile strength were tested to match the mechanical properties of the tarsus; combined with water contact angle experiments, scanning electron microscopy (SEM) observation, and Micro-CT scanning, the adaptability of the scaffold's microstructure and surface characteristics was evaluated. The aim is to achieve precise matching of material mechanical properties and biocompatibility, providing a new strategy to break through the bottleneck of eyelid defect reconstruction. 2 Materials and Methods 2.1 Scaffolds Preparation 2.1.1 Raw Materials and Equipment (1) Raw materials: Hydroxyapatite (HA), sigma-aldrich, Cat. No. 289396; Polycaprolactone (PCL), Perstorp, Sweden, Cat. No. 6800; Polyethylene glycol (PEG), Aladdin, Cat. No. P103737; Dichloromethane (DCM), Aladdin, Cat. No. D116144. (2) Equipment: Field emission environmental scanning electron microscope system (FEI Company, USA); Contact angle tester (KRUSS); Universal testing machine (CMT6104); Microfluidic bio 3D printer (Eazao Bio). 2.1.2 Preparation Method This study prepared two slurries with ratios of 84% and 70% for scaffold printing. Specifically, in a 20 ml glass vial, a specified amount of polyethylene glycol (PEG, Mn = 400) (84% ratio: 0.742 g; 70% ratio: 1.042 g) was first dissolved in 5 ml dichloromethane (DCM) and thoroughly shaken to mix. Subsequently, a corresponding amount of hydroxyapatite (HA) particles (Sigma-Aldrich, Cat. No. 289396) (84% ratio: 5.6 g; 70% ratio: 3.36 g) was added to the solution, and immediately stirred using a vortex mixer for 1 minute to initially disperse the particles. Then, a specified amount of polycaprolactone (PCL, Mn = 800,000) (84% ratio: 1.06 g; 70% ratio: 1.44 g) was added, and the mixture was stirred continuously for 12 hours to ensure complete dissolution of PCL and formation of a homogeneous slurry. The resulting slurry was transferred to a fume hood and manually stirred with a micro spatula to promote the slow evaporation of excess DCM solvent until the slurry reached a uniform viscosity suitable for printing. Finally, a pneumatic extrusion-based 3D printer equipped with a 260 µm diameter conical needle was used for scaffold forming at room temperature with an extrusion pressure of 0.4–0.5 bar. All printed scaffolds were air-dried for at least 24 hours to ensure full volatilization of residual solvent. 2.2 Structural Characterization 2.2.1. Microstructure (SEM) SEM observation was performed using a field emission environmental scanning electron microscope system (FEI Company, USA). First, the sample was fixed on a conductive sample stage and sputter-coated with a nanoscale gold layer to suppress charging effects. The FEI ESEM system was started, pumped to high vacuum (approx. 10 − 3 -10 − 4 Pa) for electron gun preheating and alignment calibration. Switching to environmental scanning mode, controlled gas was introduced to maintain stable chamber pressure. Suitable accelerating voltage (0.5–30 kV) and working distance (5–10 mm) were selected, and the sample stage displacement and tilt were adjusted to optimize contrast, brightness, and focus in real-time until the image was clear. After obtaining the images, ImageJ was used for labeling and pore size measurement. 2.2.2. Three-dimensional Pore Structure (Micro-CT) Porosity testing used Micro-CT. The scaffold was fixed at the center of the rotary stage, avoiding vibration. After performing flat field and dark field scan calibration, projection images were acquired by scanning. After selecting the ROI, analysis software was used for reconstruction and modeling, automatically generating the porosity of the corresponding scaffold. 2.2.3 Surface Hydrophilicity (Water Contact Angle) After drying the scaffolds in a constant temperature drying oven, the water contact angle of the scaffolds was tested using a contact angle tester (KRUSS) employing the sessile drop method. 2.3 Mechanical Properties Testing Mechanical properties testing was conducted using a universal testing machine (CMT6104). The scaffold (8 layers) dimensions were 29mm×8mm×1.6mm (length × width × height). A 5N sensor was selected. The scaffold was fixed on it and stretched to fracture in room temperature air at a rate of 2 mm/min. The elastic modulus of the scaffold was calculated based on the initial range of the stress-strain curve (strain range 0%-5%). 2.4 Elastic Modulus The elastic modulus (also known as Young's modulus, Elastic modulus, E) is a fundamental quantity in solid mechanics characterizing the elastic deformation properties of a material, referring to the ratio of stress to strain within the elastic deformation range. It is an inherent property of the material itself, independent of the specimen's geometric dimensions, determined solely by the material's own properties, and can be used to measure the material's ability to resist elastic deformation. Its calculation formula is as follows: $$\:E=\frac{\sigma\:}{\epsilon\:}$$ σ represents the stress applied to the material, ε represents the strain produced by the material under stress. 2.5 Statistical Methods The fundamental physicochemical properties of the scaffolds (porosity, water contact angle, density, elastic modulus, etc.) demonstrated minimal variation across different material formulations. As no intergroup comparisons were required, these parameters were presented solely through descriptive statistics. Mechanical performance data were obtained from film tensile tests, which were performed in accordance with the standard GB/T 1040.3–2006. All continuous variables (e.g., stress, strain, tensile strength) were processed using GraphPad Prism 8 software. The normality of data distribution was initially assessed through the implementation of the Shapiro-Wilk test, with a significance level of α = 0.05. For normally distributed data, between-group comparisons employed independent samples t-tests (two-tailed), with significance set at p < 0.05. Stress-strain curves were subsequently analyzed by utilizing the software's integrated graphing functionality. Subsequently, the stent Young's modulus (elastic modulus) was calculated based on the linear relationship within the stress-strain curve. 3 Results 3.1 Scaffold Appearance Macroscopic observation (Fig. 1 ) showed that both scaffold groups had good structural integrity and handleability, with regular fiber arrangement. To simulate surgical manipulation, absorbable suture knots were tied 2 mm from the scaffold edge. The scaffolds showed no significant deformation or fracture, indicating good surgical suture tolerance. 3.2 Micro-morphology (Using the 70% HA content scaffold as an example) The 70% HA content scaffold was representative for SEM observation (Fig. 2 ). At low magnification (150×), the scaffold surface appeared rough, with large pores formed between fibers, pore size approximately 570.7 µm; at high magnification (1200×), HA particles and the naturally formed microporous structures between them could be clearly identified. Random measurement of one micropore diameter was approximately 20.81 µm, indicating the scaffold has a hierarchical pore structure. 3.3 Water Contact Angle The surface wettability of the scaffolds was evaluated by water contact angle testing. The measured water contact angles for the 70% and 84% HA content scaffolds were 80.634° and 77.967°, respectively, both exhibiting hydrophilic surfaces, beneficial for cell adhesion and tissue fluid infiltration. 3.4 Three-dimensional Structure and Porosity (Using the 70% HA content scaffold as an example) The 70% HA content scaffold was scanned using Micro-CT, and its pore structure parameters were calculated (Table 1 ). The results showed that the total volume (TV) of the scaffold was 2622.12 mm³, and the solid volume (SV) was 217.58 mm³. Based on these values, the porosity (Po) was calculated to be as high as 91.66%, and the solid volume fraction (SV/TV) was 8.34%. The scaffold density (SFMD) was 38.85 mg/cm³, and the solid density (SMD) was 463.27 mg/cm³. Table 1 ༎Micro-CT scan data of the 70% HA content scaffold, calculating scaffold porosity. Parameter Name Value Volume Total Volume(TV) 2622.12 mm 3 Solid Volume(SV) 217.58 mm 3 Density Scaffold Density(SFD) 38.85 mg/cm 3 Solid Density(SD) 463.27 mg/cm 3 Percentage Solid Volume Fraction (SV/TV) 8.34% Porosity(Po) 91.66​% 3.5 Mechanical Properties Tensile tests were performed on both scaffold groups using a universal testing machine. Complete and continuous datasets were assessed for normality using the Shapiro-Wilk test. Data statistics were performed using an independent samples t-test, P = 0.0004. Subsequently, stress-strain curves were plotted using the software's built-in graphing function. The elastic modulus data were obtained by calculating the slope of the portion satisfying the linear relationship (strain range 0%-5%) in the stress-strain curve. The results are shown in Table 2 , Fig. 4 , Fig. 5 and Fig. 6 . The fracture tensile strain (εB) of the 70% HA content scaffold was 144.37 ± 6.944%, tensile strength (σM) was 0.74 ± 0.040 MPa, tensile yield stress (σy) was 0.55 ± 0.0351 MPa; the corresponding values for the 84% HA content scaffold were 91.63 ± 1.781%, 0.38 ± 0.015 MPa, and 0.32 ± 0.0153 MPa, respectively; the differences between the two scaffold groups were statistically significant in terms of tensile strain, tensile strength, and yield stress. The elastic modulus calculated from the linear segment of the stress-strain curve (strain 0%--5%) was 2.66 MPa for the 84% HA scaffold. Table 2 Detailed stress (MPa) - strain (%) raw data at the moment of tensile fracture for 70% HA content and 84% HA content samples. Breaking StrainεB/% Tensile StrengthσM/ MPa Yield Strengthσy/ MPa 70% 144.37 ± 6.944 0.74 ± 0.040 0.55 ± 0.0351 84% 91.63 ± 1. 781 0.38 ± 0.015 0.32 ± 0.0153 4 Discussion Eyelid defects are frequently attributable to malignant neoplasms, traumatic injuries, or congenital factors. These defects not only impair the patient's facial appearance and ocular surface function, precipitating a series of ocular surface diseases, but also engender psychological distress and inferiority complexes due to the altered appearance. This imposes a dual physiological and psychological burden on the patient. The clinical repair strategies employed vary considerably, contingent upon the extent of the defect. Mild defects, defined as those less than one-quarter of the total eyelid length, can often be addressed through direct approximation and suturing following local flap revision. Moderate defects, defined as those that extend from one-quarter to one-half of the total eyelid length, necessitate the utilization of graft materials such as autologous hard palate mucosa, allogeneic sclera, or auricular cartilage. However, these approaches are not without risk, including potential injury to the donor site, infection, and ethical concerns. Moreover, sole flap reconstruction frequently falls short of achieving optimal outcomes. In cases of severe defects (greater than one-half of the total eyelid length), the reconstruction process is more intricate and necessitates the separate restoration of the anterior layer, comprising the skin and subcutaneous tissue, and the posterior layer, consisting of the conjunctiva and tarsal plate. Anterior layer defects can be addressed using sliding flaps, rotation flaps, or pedicled flaps. Conjunctival defects within the posterior layer may be repaired using adjacent conjunctival flaps, while tarsal replacement still relies on autologous or allogeneic material transplantation. In instances where the defect area is exceedingly extensive, there is a marked increase in the incidence of graft failure and complications. Consequently, the development of tissue-engineered tarsal replacement materials has emerged as a prominent area of research interest. The tarsus is a semi-arcuate cartilage-fibrous composite structure approximately 1 mm thick, containing meibomian glands and a fibroblast network. It not only provides static support for the eyelid but also participates in dynamic mechanical transmission during blink movement [ 39 ] . Current clinical reconstruction methods have significant limitations [ 40 – 42 ] : Allografts like hard palate mucosa or acellular dermal matrix can avoid immune rejection but suffer from limited sources, postoperative contraction, and donor site infection issues; Xenogeneic materials like allogeneic sclera have mechanical properties close to the tarsus but are scarce, raise ethical concerns, and can easily cause chronic inflammatory reactions. The ideal tarsal substitute material should meet multiple requirements [ 43 ] : In terms of mechanical properties, it needs to possess sufficient rigidity (to maintain shape stability) and flexibility (to tolerate repeated blink loads), and its elastic modulus should match that of the natural tarsus (1.73 ± 0.61 MPa [ 44 ] ); the material surface should be conducive to cell adhesion and proliferation, and the microstructure needs high porosity (> 80%) to promote vascular ingrowth; additionally, it needs to have good surgical handleability and sterilization stability. It is worth noting that the tarsus is not typical cartilage but a cartilaginous-like fibrous tissue plate composed of meibomian glands and surrounding extracellular matrix (ECM) [ 39 ] . Its structure is similar to cartilage, suggesting that design strategies for cartilage regeneration materials can be borrowed, combined with the unique mechanical and biological requirements of the tarsus for substitute material development. This concept has been explicitly proposed by Yan et al [ 7 ] , who emphasized the need to comprehensively consider the anatomical characteristics of the defect site (such as thickness, size, and location) in tarsal reconstruction. Based on this, this study selected hydroxyapatite and polycaprolactone, widely used in bone and cartilage tissue engineering, to construct a composite scaffold material aiming to simultaneously achieve the rigid support and dynamic deformation capability required for the eyelid, thereby advancing the functional reconstruction of eyelid defect repair. In order to enhance tissue integration, it is imperative that implantable scaffolds satisfy a multitude of physical structural requirements. First, the materials used to fabricate the scaffolds should inherently possess excellent biocompatibility. In water contact angle experiments, a contact angle (CA) below 90° indicates a hydrophilic surface (where water readily spreads), while an angle above 90° signifies a hydrophobic surface (where water forms droplets). The hydrophilic surfaces of both HA/PCL scaffolds observed in this study are conducive to cell adhesion and proliferation (Fig. 3 ). Research indicates that hyaluronan surfaces effectively mediate adhesion, spreading, proliferation, and directed differentiation of various cells (e.g., osteoblasts, mesenchymal stem cells) [ 45 – 48 ] . Consequently, HA plays a crucial role in inducing and guiding bone tissue regeneration. As a result, HA has become a core biomaterial in bone tissue engineering, widely applied in scenarios such as bone replacement fillers, bone repair scaffold matrices, or coating materials. It has been demonstrated that this substance provides dual structural and biochemical signaling support for the migration, growth, and new bone matrix deposition of bone cells. Moreover, a substantial body of in vitro and in vivo evidence consistently demonstrates that synthetic HA materials exhibit excellent biocompatibility, with no significant toxicity, non-sensitizing properties, and non-mutagenicity, along with favorable tissue integration. It has been demonstrated to form strong chemical bonds with host bone tissue and coexist harmoniously with blood components and surrounding soft tissues, thereby effectively reducing the risk of implant-related immune rejection. This provides an optimized biointerface and reliable regenerative healing environment for diverse clinical applications, including large-area bone defect repair, spinal/joint fusion, maxillofacial reconstruction, and orbital implants (e.g., prosthetic sockets). PCL is a synthetic polyester with excellent biocompatibility that has been approved by the U.S. Food and Drug Administration (FDA) for human medical applications. Its chemical inertness prevents it from triggering severe immune reactions or toxic effects when in contact with biological tissues [ 49 , 50 ] , and its ability to promote cell adhesion and proliferation is comparable to that of human amniotic membrane [ 51 ] . The capacity to promote cell adhesion and proliferation is particularly evident in the corneal epithelium [ 51 – 54 ] , stroma [ 55 – 57 ] , and endothelium [ 58 – 60 ] , further demonstrating the favorable biological effects of PCL on the ocular surface. Secondly, the prepared scaffolds should exhibit a rough surface and a loose, porous structure at the microscopic level. The rough surface of the material in question has been shown to facilitate cell adhesion and proliferation on the scaffold, while the loose, porous structure of the material has been demonstrated to promote microvascular ingrowth into the scaffold. Collectively, these characteristics enhance the overall biocompatibility and tissue integration of the scaffold, thereby improving transplantation success rates. It is noteworthy that the two scaffolds with varying HA ratios, as discussed in this study, exhibited no substantial difference in porosity. Given the correlation between porosity and the preparation process, the present study focuses exclusively on the porosity data for the 70% HA content scaffold, as depicted in the SEM images. The surface roughness of the scaffolds in this study is clearly observable in the scanning electron micrograph (Fig. 2 ). At 1200× magnification, micro-pores between hydroxyapatite particles are directly visible. The porosity of the implant directly correlates with the extent of vascular ingrowth within the implant and the subsequent integration between the implant and the surrounding tissues. In most cases, pore volumes exceed 80% [ 45 , 61 , 62 ] . The following text is intended to provide a comprehensive overview of the subject matter. The HA/PCL scaffold in this study demonstrated a porosity of 91.66%, as indicated in Table 1 . The structural characteristics of this material, namely its loose and porous nature, have been demonstrated to facilitate microvascular ingrowth into the voids, enhance tarsal tissue integration, and promote local metabolism. The pore size of the graft is also closely related to its vascularization and tissue integration. The porosity of grafts utilized for distinct tissues exhibits variability, with different pore sizes being optimal for specific applications. Despite the absence of a consensus on the optimal pore size for bone regeneration, the conclusions drawn are largely congruent. Pores measuring less than 100 µm have been shown to promote cell aggregation and cell-matrix interactions, thereby mimicking the dense ECM structure of natural cartilage [ 63 – 65 ] . As Sánchez-Salcedo et al [ 66 ] have observed, pore sizes ranging from 100 to 1000 µm have been shown to promote cell proliferation, bone tissue ingrowth, and the provision of mechanical strength. Additionally, research by Gupte et al [ 67 ] found that large pore sizes ranging from 400 to 625 µm in cartilage regeneration scaffolds facilitate vascular ingrowth and promote scaffold vascularization. In summary, smaller pore sizes (less than 100 µm) encourage cell adhesion and proliferation on the scaffold during transplantation. This facilitates ECM formation at the implantation site. Larger pore sizes (100–1,000 µm) allow for vascular ingrowth into the scaffold, which promotes vascularization and enhances overall tissue integration. In this study, the HA/PCL scaffold's pore size characteristics were achieved through hierarchical regulation. Large pores (approximately 500 µm) were manually controlled, and small pores (< 50 µm) formed as natural voids through HA particle stacking after solvent evaporation. From a functional compatibility perspective, this structure theoretically ensures the cell adhesion efficiency necessary for tarsal plate repair and the capacity for angiogenesis. Ultimately, this promotes integration between the scaffold and the tissue of the tarsal plate. Moreover, in the context of repairing eyelid defects using scaffold grafts, it is imperative that the scaffold adheres to the "like-for-like" principle [ 1 , 6 , 7 ] . This principle stipulates that the replacement material must closely match the original state of the defective tissue in both structural characteristics and biological function. The eyelid is a specialized functional structure that is characterized by two distinctive structural features. Firstly, it possesses rigid support capacity and flexible deformation potential. This characteristic is primarily determined by the structure and mechanical properties of the internal tarsal plate. From a quantitative characterization perspective, the elastic modulus of the tarsal plate is the sole mechanical parameter that comprehensively reflects its rigid support effect and flexible deformation capacity. Sun et al [ 44 ] obtained an average elastic modulus of 1.73 ± 0.61 MPa for human tarsal plates through measurements of fresh human tarsal tissue. The elastic modulus of the scaffold must be meticulously regulated within an optimal range. Insufficient control of this parameter can lead to two unfavorable outcomes: an excessively rigid material with inadequate deformation capacity, resulting in an inability to accommodate the flexible deformation requirements of the eyelid; or an excessively flexible material, which is incapable of providing the necessary rigid support function for tarsal plate repair. Furthermore, the scaffold with 70% HA content demonstrated higher fracture tensile strain and tensile strength (Fig. 4 ), suggesting superior ductility and toughness. This phenomenon is primarily attributed to the enhanced plastic deformation capacity imparted by the relatively higher contents of PCL and PEG400. However, in the context of eyelid tarsal plate repair, the primary objective is not merely to achieve high strength or high elongation. The primary challenge lies in ascertaining whether the material can provide adequate static support while also meeting the dynamic flexibility demands of eyelid blinking movements. In summary, as the elastic modulus of the graft scaffold approaches that of the natural tarsal plate, the higher the mechanical compatibility between the scaffold and the plate, thereby better meeting the physiological and mechanical demands of the tarsal plate. For the two HA/PCL scaffolds with different ratios prepared in this study (Fig. 6 ), the 84% HA scaffold exhibited an elastic modulus of 2.66 MPa. This value is mechanically closer to the elastic modulus range of the tarsal plate, demonstrating superior alignment with the plate's inherent mechanical properties. Consequently, it is more likely to meet the mechanical compatibility requirements for tarsal plate reconstruction. HA is a frequently utilized material in the regeneration of bone and cartilage. It demonstrates a low degradation rate in vivo [ 68 , 69 ] and may persist for several years [ 61 ] . In vitro degradation studies by Navarrete-Segado et al [ 70 ] analyzed the behavior of HA scaffolds in 0.05 M TRIS buffer solution (initial pH 7.3 ± 0.1) at 37 ± 1°C. Specifically, the pH exhibited a decline from 7.3 to 7.24 over a 72-hour period, with a variation of less than ± 0.3, suggesting that scaffold degradation exerts minimal influence on the surrounding pH milieu. Scaffold weight loss exhibited a gradual increase with immersion time, reaching a mere 0.12% of total mass after 72 hours, indicative of minimal mass depletion. Concurrently, inductively coupled plasma atomic emission spectroscopy (ICP/AES) analysis revealed a low calcium ion release of 1.26 milligrams per liter over 72 hours. Collectively, these results confirm the slow degradation characteristics of this HA scaffold, providing experimental support for its application in small or non-load-bearing implant scenarios requiring gradual absorption. This approach is consistent with the established criteria for eyelid defect repair. Eyelid tissue is a thin-layered, non-load-bearing, delicate structure. The slow degradation characteristics of HA scaffolds precisely match the temporal progression of eyelid soft tissue regeneration. These cells provide a structural framework for the migration of cells and the deposition of the extracellular matrix over an extended period. Concurrently, the incremental release of calcium ions in low concentrations exerts a gentle modulatory effect on the local microenvironment, thereby promoting fibroblast activity and collagen synthesis without inducing mineral deposition or ectopic calcification risks. Moreover, eyelid repair generally entails scenarios involving small-scale, low-mechanical-load implantation, which does not necessitate the utilization of materials characterized by high strength or rapid degradation capabilities. Conversely, the phenomenon of gradual mass loss and ion release has been demonstrated to facilitate synchronized metabolic integration between the material and surrounding tissues. This approach prevents premature degradation-induced support failure or prolonged retention-induced chronic foreign body reactions, thereby jointly supporting the stable reconstruction of eyelid function and morphology at both structural and biological levels. Despite the study's success in fabricating a flexible, conformable PEG400-plasticized HA/PCL composite scaffold through material modification and 3D printing technology, and its systematic characterization of physicochemical properties, several limitations persist. The present work is chiefly oriented towards material preparation and property characterization, with a conspicuous absence of cell compatibility evaluations or in vivo animal experiments. Consequently, the scaffold's in vivo degradation behavior, tissue integration capacity, and long-term repair efficacy remain to be assessed. This deficiency hinders a comprehensive understanding of the immune responses, vascularization processes, and functional restoration impacts the material may induce in real biological environments, such as eyelid defect models. Moreover, the dearth of in vivo experimental data impedes comprehensive analysis of the scaffold's mechanical property evolution and degradation/metabolism pathways within dynamic physiological environments. Future research should systematically conduct cell compatibility studies to confirm the biocompatibility of this scaffold material. Concurrently, the establishment of appropriate animal models (e.g., rabbit or rat eyelid defect models) is imperative to comprehensively evaluate the efficacy of the repair procedure across histological, biomechanical, and functional recovery dimensions. This will provide more robust experimental evidence for clinical translation. Building upon this foundation, comprehensive mechanical property optimization can be achieved by further refining the printing process (e.g., regulating fiber orientation), incorporating more efficient plasticizers, adjusting composite material ratios, or constructing finer multi-level composite structures. These approaches have been shown to enhance tensile strength and toughness while maintaining the material's optimal elastic modulus. 5 Conclusion The present study successfully fabricated PEG400-plasticized HA/PCL composite scaffolds using pneumatic extrusion 3D printing technology. The physicochemical properties of the fabricated materials were systematically evaluated, and the potential of the materials as a replacement material for the posterior eyelid layer was determined. The findings suggest that the scaffold with 84% HA content demonstrates superior comprehensive properties: its elastic modulus of 2.66 MPa closely matches the natural mechanical properties of human tarsal plates (1.73 ± 0.61 MPa), concurrently meeting the mechanical demands of static support and dynamic blinking. The multi-level pore structure and high porosity provide an ideal microenvironment for cell adhesion, nutrient transport, and vascular ingrowth; the hydrophilic surface further enhances its biocompatibility. Furthermore, the gradual degradation profile of HA corresponds to the non-weight-bearing characteristics of the eyelid and its prolonged regeneration cycle, thereby enabling synchronized integration and reconstruction between the implant and host tissue. A comprehensive evaluation of the material's performance was conducted, which revealed that the 84% HA/PCL scaffold is more suitable for eyelid defect repair. Despite the notable advancements made in material design and performance characterization in this study, further validation of its biological properties and repair efficacy through cellular and animal experiments remains imperative. In summary, the PEG400-plasticized HA/PCL composite scaffold under consideration exhibits considerable promise as a tarsal plate replacement material for the eyelid. This potential is supported by its demonstrated mechanical adaptability, structural characteristics, and degradation behavior. These attributes provide substantial evidence to support the conduct of subsequent clinical translation studies. Abbreviations HA Hydroxyapatite PCL Polycaprolactone ECM Extracellular Matrix PEG Polyethylene Glycol SEM Scanning Electron Microscopy DCM Dichloromethane TV Total Volume SV Solid Volume SFD Scaffold Density SD Solid Density Po Porosity Declarations Acknowledgements The authors would like to thank the colleagues from the School of Optometry and the School of Advanced Manufacturing at Nanchang University for their insightful discussions and technical support. We are also grateful for the access to the experimental facilities provided by the Jiangxi Provincial Key Laboratory for Ophthalmology and the National Clinical Research Center for Ocular Diseases Jiangxi Province Division. Author contributions Jincheng Liu and Simeng Lv: Contributed equally to this work as co-first authors; involved in methodology, investigation, and writing - original draft. Mengling Zhou, Mange Zhang, Qingyi Wang, Yangbin Fang, and Yao Lai: Participated in formal analysis, validation, and data curation. Fanrong Ai and Qin Huang: Served as co-corresponding authors; responsible for conceptualization, supervision, project administration, funding acquisition, and writing - review & editing. All authors have reviewed and approved the final manuscript. Data availability statement The datasets generated and analyzed during the current study are available from the corresponding authors on reasonable request. The data supporting the findings of this research are not publicly available due to privacy or ethical restrictions but can be accessed for academic and non-commercial purposes upon request. Funding This work was supported by the Natural Science Foundation of Jiangxi Province (Grant No.20242BAB5490). Declaration of interests The authors declare no competing interests. References Chang, E. I., Esmaeli, B. & Butler, C. E. Eyelid Reconstruction[J/OL]. Plast. Reconstr. Surg. 140 (5), 724e–735e. 10.1097/PRS.0000000000003820 (2017). Verity, D. H. & Collin, J. R. O. 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19:13:43","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":167805,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7969055/v1/44a2ba15fcacf3215ca3907f.html"},{"id":97921145,"identity":"da6da9ee-5505-4497-822b-9b1ce9fa8ae2","added_by":"auto","created_at":"2025-12-10 19:13:42","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":179172,"visible":true,"origin":"","legend":"\u003cp\u003eOverall appearance of the scaffolds; a: Scaffold with 70% HA content, slightly yellowish; b: Scaffold with 84% HA content, white in color.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7969055/v1/b5563f91f7c23a325b5eea39.jpeg"},{"id":97921138,"identity":"3fa99c7a-7ba0-434e-a2a2-2c211b64fa04","added_by":"auto","created_at":"2025-12-10 19:13:42","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":188743,"visible":true,"origin":"","legend":"\u003cp\u003eSEM images of the 70% HA content scaffold. a: Magnification 150× shows the rough scaffold surface, large pores visible between scaffold fibers (measured pore diameter approx. 570.7μm); b: Magnification 1200× shows HA particles in the scaffold (yellow arrows) and small pores between particles (green arrows, randomly measured diameter of one micropore approx. 20.81μm).\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7969055/v1/e7a83d4260525fd4f98dd814.jpeg"},{"id":98421374,"identity":"21b8f5b7-b858-447c-88be-08a5797fed7e","added_by":"auto","created_at":"2025-12-17 16:26:55","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":161716,"visible":true,"origin":"","legend":"\u003cp\u003eWater Contact Angle (CA) experimental results. a: CA of the 70% HA content scaffold is 80.634°; b: CA of the 84% HA content scaffold is 77.967°.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7969055/v1/be9fe23d9d6d5a23442bd53b.png"},{"id":97921140,"identity":"334c01e7-e429-4a82-831a-ca8f52715e77","added_by":"auto","created_at":"2025-12-10 19:13:42","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":44574,"visible":true,"origin":"","legend":"\u003cp\u003eTensile strain: 70% HA scaffold group significantly higher than 84% group (P \u0026lt; 0.0001); Tensile strength: 70% group significantly higher than 84% group (P \u0026lt; 0.01); Yield strength: 70% group significantly higher than 84% group (P \u0026lt; 0.0001).\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7969055/v1/3af77f32889b2a79ffbca15f.png"},{"id":98421300,"identity":"160938e3-c190-45b3-85ff-354a5ab188da","added_by":"auto","created_at":"2025-12-17 16:26:26","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":20111,"visible":true,"origin":"","legend":"\u003cp\u003eStress-Strain Curves of Two Scaffolds: the red line represents the 70% HA scaffold,\u003c/p\u003e\n\u003cp\u003eand the black line denotes the 84% HA scaffold.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7969055/v1/36ff7d2d41789e6a0d16ceef.png"},{"id":97921143,"identity":"da7f0049-819a-4693-ad4a-1cb234ea987b","added_by":"auto","created_at":"2025-12-10 19:13:42","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":45556,"visible":true,"origin":"","legend":"\u003cp\u003eElastic modulus data were calculated as the slope of the linear region (strain range: 0%-5%) in stress-strain curves.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-7969055/v1/cf7526aed71dbf67324ccf70.png"},{"id":98443409,"identity":"3a6ea029-86a3-4d4f-a9fd-57d5299b7859","added_by":"auto","created_at":"2025-12-17 17:13:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1564344,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7969055/v1/5cb84ed8-55b5-4451-9cb0-9f629fabc887.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Extrusion-based 3D Printing of PEG400-Plasticized HA/PCL Composite Scaffolds: A Study on Flexible Adaptation for Eyelid Defect Repair","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eThe eyelid is a crucial structure for maintaining ocular health and facial aesthetics, with physiological functions encompassing three key dimensions: protecting the eyeball from external damage, maintaining a moist ocular surface environment to ensure transparency of optical media, and participating in the formation of dynamic facial expressions\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Anatomically\u003csup\u003e[\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e, the eyelid consists of an anterior skin-muscle layer and a posterior tarsoconjunctival layer, forming a precise functional complex. The anterior layer includes the skin and orbicularis oculi muscle, responsible for blink function and shaping the external contour; the posterior layer is composed of the tarsus and palpebral conjunctiva, providing core mechanical support and ocular surface lubrication. This anatomical layering specificity dictates that reconstruction surgery must strictly adhere to the \"Like for like\" principle\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e, meaning substitute materials must highly match the original state of the defective tissue in both structural characteristics and biological function. Therefore, the repair of posterior lamellar eyelid defects constitutes a core challenge in clinical treatment.\u003c/p\u003e\u003cp\u003eHydroxyapatite (HA) is the main inorganic component of human bone (50\u0026ndash;70%). Its hexagonal crystal system structure (space group P6\u003csub\u003e3\u003c/sub\u003e/m) shares chemical and crystallographic homology with natural bone mineral, forming the basis of its biological function. The Ca\u003csup\u003e2+\u003c/sup\u003e, PO\u003csub\u003e4\u003c/sub\u003e\u003csup\u003e3\u0026minus;\u003c/sup\u003e, and OH\u003csup\u003e\u0026minus;\u003c/sup\u003e ions in its chemical formula Ca\u003csub\u003e10\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e are all endogenous, avoiding implantation toxicity\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. HA particles, due to their high specific surface area and biomimetic mineral characteristics, enhance surface and interface effects, demonstrating superior cell adhesion, proliferation, and differentiation regulation capabilities compared to ordinary HA, which is crucial for bone regeneration\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. HA, as a brittle polycrystalline material, has mechanical properties (strength, toughness, etc.) comprehensively influenced by factors such as grain size, crystallinity, grain boundary state, chemical composition, and porosity\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Its brittleness originates from its strong ionic bond structure, leading to poor plastic deformation ability and sensitivity to microcracks, making it prone to fracture under load. Processes like sintering can reduce grain size to improve strength and toughness, as fine-grained structures have fewer grain boundary defects\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. High crystallinity and low porosity can enhance stiffness, tensile/compressive strength, and fracture toughness; conversely, amorphous phases or porous structures weaken mechanical performance\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. In bone repair, the success of HA composites relies on mechanical adaptability and promoting angiogenesis. Strength can be improved by introducing organic polymers (e.g., collagen, polylactic acid) or inorganic reinforcing phases (e.g., bioactive glass, calcium phosphate) \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTherefore, inorganic/organic composite materials show significant application potential due to their adjustable tissue adaptability and functional designability. Early preparation methods involving direct mixing of HA and polymers suffered from issues like uneven phase distribution and weak interfacial bonding, but advanced techniques (e.g., in-situ deposition, freeze-drying, 3D printing) have effectively broken through this bottleneck\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. HA has good biocompatibility, promoting cell attachment, growth, and differentiation\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Compositing with collagen, polylactic acid, etc., can further enhance biocompatibility and mechanical properties, promoting osseointegration\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Its applications have expanded to drug delivery, biosensing, and regenerative medicine\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. By controlling synthesis conditions (e.g., pH, temperature), its microstructure and properties can be precisely optimized, and fiber composite strategies can also improve the brittleness of traditional HA-based scaffolds.\u003c/p\u003e\u003cp\u003ePolycaprolactone (PCL) is a synthetic aliphatic polyester with excellent mechanical properties, controlled degradability, and biocompatibility, making it widely used in tissue engineering\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. Its tensile modulus (343.9-363.4 MPa) and compressive strength (216 MPa) are comparable to those of natural bone, making it suitable for bone and cartilage regeneration. Its degradation cycle exceeds two years, and its degradation products are non-toxic, having been approved by the FDA for use in implants and scaffolds\u003csup\u003e[\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. However, PCL's inherent hydrophobicity hinders cell adhesion, often necessitating surface modification (e.g., plasma treatment or hydrophilic coating) to enhance bioactivity\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. In regard to the processing stage, the thermoplasticity and melt stability of PCLs serve to facilitate the implementation of a variety of advanced manufacturing technologies. Three-dimensional printing (e.g., fused deposition modeling) has the capacity to construct high-precision microstructural scaffolds that are suitable for bone defect repair\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. Electrospinning can produce nanofibers (diameter 75\u0026ndash;344 nm) to promote cell infiltration\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Furthermore, particle impregnation has the potential to produce high-porosity (85\u0026ndash;88%) foam scaffolds that can provide mechanical support for soft tissues\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn the domain of tissue engineering, PCL scaffolds exhibit a wide range of applications. In the field of dermatology, PCL electrospun membranes have been shown to mimic the extracellular matrix (ECM). These membranes exhibit high porosity (\u0026gt;\u0026thinsp;90%) and hydrophilic modification, which has been demonstrated to promote keratinocyte proliferation and wound healing\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. In the field of bone regeneration, PCL scaffolds loaded with drugs, such as metformin, have been shown to promote osteoblast differentiation and mineralization. The integration of 3D printing technology allows for the fabrication of customized pore structures, which can be tailored to specific biological requirements\u003csup\u003e[\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. In the domain of vascular engineering, PCL-based grafts, including small-diameter vessels, when combined with heparin coating, have demonstrated the capacity to enhance anticoagulant properties and endothelial growth. These grafts exhibit mechanical properties that satisfy the physiological pressure requirements of the vasculature\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e. In the context of neural repair, PCL nanofiber scaffolds have been observed to improve Schwann cell adhesion by reducing fiber diameter. 180 nm), and gold nanoparticle doping has been demonstrated to facilitate conductivity, thereby promoting axon regeneration\u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eCurrent PCL research focuses on functionalization and intelligent design: drug delivery systems utilize PCL nanoparticles to load anticancer drugs and improve targeting through surface modification\u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e; 4D printing combined with shape memory PCL can construct dynamically responsive scaffolds (e.g., simulating lung expansion) for respiratory tissue engineering\u003csup\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e; emerging directions include mussel protein functionalization to enhance osseointegration\u003csup\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/sup\u003e, and developing conductive composite materials for neural regulation\u003csup\u003e[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e, promoting the development of personalized medicine. These advances indicate that PCL is evolving from a traditional scaffold to a multifunctional therapeutic platform.\u003c/p\u003e\u003cp\u003eGiven the adjustable mechanical properties and structural freedom of synthetic polymer composites, this study proposes a composite scaffold system based on polycaprolactone/hydroxyapatite (PCL/HA), constructing a porous structure through pneumatic extrusion technology and introducing polyethylene glycol (PEG) to regulate material toughness. The elastic modulus and tensile strength were tested to match the mechanical properties of the tarsus; combined with water contact angle experiments, scanning electron microscopy (SEM) observation, and Micro-CT scanning, the adaptability of the scaffold's microstructure and surface characteristics was evaluated. The aim is to achieve precise matching of material mechanical properties and biocompatibility, providing a new strategy to break through the bottleneck of eyelid defect reconstruction.\u003c/p\u003e"},{"header":"2 Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Scaffolds Preparation\u003c/h2\u003e\u003cdiv id=\"Sec4\" class=\"Section3\"\u003e\u003ch2\u003e2.1.1 Raw Materials and Equipment\u003c/h2\u003e\u003cp\u003e(1) Raw materials: Hydroxyapatite (HA), sigma-aldrich, Cat. No. 289396; Polycaprolactone (PCL), Perstorp, Sweden, Cat. No. 6800; Polyethylene glycol (PEG), Aladdin, Cat. No. P103737; Dichloromethane (DCM), Aladdin, Cat. No. D116144.\u003c/p\u003e\u003cp\u003e(2) Equipment: Field emission environmental scanning electron microscope system (FEI Company, USA); Contact angle tester (KRUSS); Universal testing machine (CMT6104); Microfluidic bio 3D printer (Eazao Bio).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section3\"\u003e\u003ch2\u003e2.1.2 Preparation Method\u003c/h2\u003e\u003cp\u003eThis study prepared two slurries with ratios of 84% and 70% for scaffold printing. Specifically, in a 20 ml glass vial, a specified amount of polyethylene glycol (PEG, Mn\u0026thinsp;=\u0026thinsp;400) (84% ratio: 0.742 g; 70% ratio: 1.042 g) was first dissolved in 5 ml dichloromethane (DCM) and thoroughly shaken to mix. Subsequently, a corresponding amount of hydroxyapatite (HA) particles (Sigma-Aldrich, Cat. No. 289396) (84% ratio: 5.6 g; 70% ratio: 3.36 g) was added to the solution, and immediately stirred using a vortex mixer for 1 minute to initially disperse the particles. Then, a specified amount of polycaprolactone (PCL, Mn\u0026thinsp;=\u0026thinsp;800,000) (84% ratio: 1.06 g; 70% ratio: 1.44 g) was added, and the mixture was stirred continuously for 12 hours to ensure complete dissolution of PCL and formation of a homogeneous slurry. The resulting slurry was transferred to a fume hood and manually stirred with a micro spatula to promote the slow evaporation of excess DCM solvent until the slurry reached a uniform viscosity suitable for printing. Finally, a pneumatic extrusion-based 3D printer equipped with a 260 \u0026micro;m diameter conical needle was used for scaffold forming at room temperature with an extrusion pressure of 0.4\u0026ndash;0.5 bar. All printed scaffolds were air-dried for at least 24 hours to ensure full volatilization of residual solvent.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Structural Characterization\u003c/h2\u003e\u003cdiv id=\"Sec7\" class=\"Section3\"\u003e\u003ch2\u003e2.2.1. Microstructure (SEM)\u003c/h2\u003e\u003cp\u003eSEM observation was performed using a field emission environmental scanning electron microscope system (FEI Company, USA). First, the sample was fixed on a conductive sample stage and sputter-coated with a nanoscale gold layer to suppress charging effects. The FEI ESEM system was started, pumped to high vacuum (approx. 10\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003e-10\u003csup\u003e\u0026minus;\u0026thinsp;4\u003c/sup\u003e Pa) for electron gun preheating and alignment calibration. Switching to environmental scanning mode, controlled gas was introduced to maintain stable chamber pressure. Suitable accelerating voltage (0.5\u0026ndash;30 kV) and working distance (5\u0026ndash;10 mm) were selected, and the sample stage displacement and tilt were adjusted to optimize contrast, brightness, and focus in real-time until the image was clear. After obtaining the images, ImageJ was used for labeling and pore size measurement.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section3\"\u003e\u003ch2\u003e2.2.2. Three-dimensional Pore Structure (Micro-CT)\u003c/h2\u003e\u003cp\u003ePorosity testing used Micro-CT. The scaffold was fixed at the center of the rotary stage, avoiding vibration. After performing flat field and dark field scan calibration, projection images were acquired by scanning. After selecting the ROI, analysis software was used for reconstruction and modeling, automatically generating the porosity of the corresponding scaffold.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section3\"\u003e\u003ch2\u003e2.2.3 Surface Hydrophilicity (Water Contact Angle)\u003c/h2\u003e\u003cp\u003eAfter drying the scaffolds in a constant temperature drying oven, the water contact angle of the scaffolds was tested using a contact angle tester (KRUSS) employing the sessile drop method.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Mechanical Properties Testing\u003c/h2\u003e\u003cp\u003eMechanical properties testing was conducted using a universal testing machine (CMT6104). The scaffold (8 layers) dimensions were 29mm\u0026times;8mm\u0026times;1.6mm (length \u0026times; width \u0026times; height). A 5N sensor was selected. The scaffold was fixed on it and stretched to fracture in room temperature air at a rate of 2 mm/min. The elastic modulus of the scaffold was calculated based on the initial range of the stress-strain curve (strain range 0%-5%).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Elastic Modulus\u003c/h2\u003e\u003cp\u003eThe elastic modulus (also known as Young's modulus, Elastic modulus, E) is a fundamental quantity in solid mechanics characterizing the elastic deformation properties of a material, referring to the ratio of stress to strain within the elastic deformation range. It is an inherent property of the material itself, independent of the specimen's geometric dimensions, determined solely by the material's own properties, and can be used to measure the material's ability to resist elastic deformation. Its calculation formula is as follows:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:E=\\frac{\\sigma\\:}{\\epsilon\\:}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eσ represents the stress applied to the material, ε represents the strain produced by the material under stress.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e2.5 Statistical Methods\u003c/h2\u003e\u003cp\u003eThe fundamental physicochemical properties of the scaffolds (porosity, water contact angle, density, elastic modulus, etc.) demonstrated minimal variation across different material formulations. As no intergroup comparisons were required, these parameters were presented solely through descriptive statistics. Mechanical performance data were obtained from film tensile tests, which were performed in accordance with the standard GB/T 1040.3\u0026ndash;2006. All continuous variables (e.g., stress, strain, tensile strength) were processed using GraphPad Prism 8 software. The normality of data distribution was initially assessed through the implementation of the Shapiro-Wilk test, with a significance level of α\u0026thinsp;=\u0026thinsp;0.05. For normally distributed data, between-group comparisons employed independent samples t-tests (two-tailed), with significance set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Stress-strain curves were subsequently analyzed by utilizing the software's integrated graphing functionality. Subsequently, the stent Young's modulus (elastic modulus) was calculated based on the linear relationship within the stress-strain curve.\u003c/p\u003e\u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Scaffold Appearance\u003c/h2\u003e\u003cp\u003eMacroscopic observation (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) showed that both scaffold groups had good structural integrity and handleability, with regular fiber arrangement. To simulate surgical manipulation, absorbable suture knots were tied 2 mm from the scaffold edge. The scaffolds showed no significant deformation or fracture, indicating good surgical suture tolerance.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Micro-morphology (Using the 70% HA content scaffold as an example)\u003c/h2\u003e\u003cp\u003eThe 70% HA content scaffold was representative for SEM observation (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). At low magnification (150\u0026times;), the scaffold surface appeared rough, with large pores formed between fibers, pore size approximately 570.7 \u0026micro;m; at high magnification (1200\u0026times;), HA particles and the naturally formed microporous structures between them could be clearly identified. Random measurement of one micropore diameter was approximately 20.81 \u0026micro;m, indicating the scaffold has a hierarchical pore structure.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Water Contact Angle\u003c/h2\u003e\u003cp\u003eThe surface wettability of the scaffolds was evaluated by water contact angle testing. The measured water contact angles for the 70% and 84% HA content scaffolds were 80.634\u0026deg; and 77.967\u0026deg;, respectively, both exhibiting hydrophilic surfaces, beneficial for cell adhesion and tissue fluid infiltration.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003e3.4 Three-dimensional Structure and Porosity (Using the 70% HA content scaffold as an example)\u003c/h2\u003e\u003cp\u003eThe 70% HA content scaffold was scanned using Micro-CT, and its pore structure parameters were calculated (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The results showed that the total volume (TV) of the scaffold was 2622.12 mm\u0026sup3;, and the solid volume (SV) was 217.58 mm\u0026sup3;. Based on these values, the porosity (Po) was calculated to be as high as 91.66%, and the solid volume fraction (SV/TV) was 8.34%. The scaffold density (SFMD) was 38.85 mg/cm\u0026sup3;, and the solid density (SMD) was 463.27 mg/cm\u0026sup3;.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e༎Micro-CT scan data of the 70% HA content scaffold, calculating scaffold porosity.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eName\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eValue\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVolume\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal Volume(TV)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2622.12 mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSolid Volume(SV)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e217.58 mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDensity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eScaffold Density(SFD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.85 mg/cm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSolid Density(SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e463.27 mg/cm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePercentage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSolid Volume Fraction (SV/TV)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.34%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePorosity(Po)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e91.66​%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003e3.5 Mechanical Properties\u003c/h2\u003e\u003cp\u003eTensile tests were performed on both scaffold groups using a universal testing machine. Complete and continuous datasets were assessed for normality using the Shapiro-Wilk test. Data statistics were performed using an independent samples t-test, P\u0026thinsp;=\u0026thinsp;0.0004. Subsequently, stress-strain curves were plotted using the software's built-in graphing function. The elastic modulus data were obtained by calculating the slope of the portion satisfying the linear relationship (strain range 0%-5%) in the stress-strain curve. The results are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e. The fracture tensile strain (εB) of the 70% HA content scaffold was 144.37\u0026thinsp;\u0026plusmn;\u0026thinsp;6.944%, tensile strength (σM) was 0.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.040 MPa, tensile yield stress (σy) was 0.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0351 MPa; the corresponding values for the 84% HA content scaffold were 91.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.781%, 0.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.015 MPa, and 0.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0153 MPa, respectively; the differences between the two scaffold groups were statistically significant in terms of tensile strain, tensile strength, and yield stress. The elastic modulus calculated from the linear segment of the stress-strain curve (strain 0%--5%) was 2.66 MPa for the 84% HA scaffold.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDetailed stress (MPa) - strain (%) raw data at the moment of tensile fracture for 70% HA content and 84% HA content samples.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBreaking StrainεB/%\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTensile StrengthσM/ MPa\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYield Strengthσy/ MPa\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e70%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e144.37\u0026thinsp;\u0026plusmn;\u0026thinsp;6.944\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.040\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e0.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0351\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e84%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e91.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1. 781\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e0.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0153\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eEyelid defects are frequently attributable to malignant neoplasms, traumatic injuries, or congenital factors. These defects not only impair the patient's facial appearance and ocular surface function, precipitating a series of ocular surface diseases, but also engender psychological distress and inferiority complexes due to the altered appearance. This imposes a dual physiological and psychological burden on the patient.\u003c/p\u003e\u003cp\u003eThe clinical repair strategies employed vary considerably, contingent upon the extent of the defect. Mild defects, defined as those less than one-quarter of the total eyelid length, can often be addressed through direct approximation and suturing following local flap revision. Moderate defects, defined as those that extend from one-quarter to one-half of the total eyelid length, necessitate the utilization of graft materials such as autologous hard palate mucosa, allogeneic sclera, or auricular cartilage. However, these approaches are not without risk, including potential injury to the donor site, infection, and ethical concerns. Moreover, sole flap reconstruction frequently falls short of achieving optimal outcomes. In cases of severe defects (greater than one-half of the total eyelid length), the reconstruction process is more intricate and necessitates the separate restoration of the anterior layer, comprising the skin and subcutaneous tissue, and the posterior layer, consisting of the conjunctiva and tarsal plate. Anterior layer defects can be addressed using sliding flaps, rotation flaps, or pedicled flaps. Conjunctival defects within the posterior layer may be repaired using adjacent conjunctival flaps, while tarsal replacement still relies on autologous or allogeneic material transplantation. In instances where the defect area is exceedingly extensive, there is a marked increase in the incidence of graft failure and complications. Consequently, the development of tissue-engineered tarsal replacement materials has emerged as a prominent area of research interest.\u003c/p\u003e\u003cp\u003eThe tarsus is a semi-arcuate cartilage-fibrous composite structure approximately 1 mm thick, containing meibomian glands and a fibroblast network. It not only provides static support for the eyelid but also participates in dynamic mechanical transmission during blink movement\u003csup\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e. Current clinical reconstruction methods have significant limitations\u003csup\u003e[\u003cspan additionalcitationids=\"CR41\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/sup\u003e: Allografts like hard palate mucosa or acellular dermal matrix can avoid immune rejection but suffer from limited sources, postoperative contraction, and donor site infection issues; Xenogeneic materials like allogeneic sclera have mechanical properties close to the tarsus but are scarce, raise ethical concerns, and can easily cause chronic inflammatory reactions. The ideal tarsal substitute material should meet multiple requirements\u003csup\u003e[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/sup\u003e: In terms of mechanical properties, it needs to possess sufficient rigidity (to maintain shape stability) and flexibility (to tolerate repeated blink loads), and its elastic modulus should match that of the natural tarsus (1.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61 MPa\u003csup\u003e[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/sup\u003e); the material surface should be conducive to cell adhesion and proliferation, and the microstructure needs high porosity (\u0026gt;\u0026thinsp;80%) to promote vascular ingrowth; additionally, it needs to have good surgical handleability and sterilization stability.\u003c/p\u003e\u003cp\u003eIt is worth noting that the tarsus is not typical cartilage but a cartilaginous-like fibrous tissue plate composed of meibomian glands and surrounding extracellular matrix (ECM) \u003csup\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e. Its structure is similar to cartilage, suggesting that design strategies for cartilage regeneration materials can be borrowed, combined with the unique mechanical and biological requirements of the tarsus for substitute material development. This concept has been explicitly proposed by Yan et al\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e, who emphasized the need to comprehensively consider the anatomical characteristics of the defect site (such as thickness, size, and location) in tarsal reconstruction. Based on this, this study selected hydroxyapatite and polycaprolactone, widely used in bone and cartilage tissue engineering, to construct a composite scaffold material aiming to simultaneously achieve the rigid support and dynamic deformation capability required for the eyelid, thereby advancing the functional reconstruction of eyelid defect repair.\u003c/p\u003e\u003cp\u003eIn order to enhance tissue integration, it is imperative that implantable scaffolds satisfy a multitude of physical structural requirements. First, the materials used to fabricate the scaffolds should inherently possess excellent biocompatibility. In water contact angle experiments, a contact angle (CA) below 90\u0026deg; indicates a hydrophilic surface (where water readily spreads), while an angle above 90\u0026deg; signifies a hydrophobic surface (where water forms droplets). The hydrophilic surfaces of both HA/PCL scaffolds observed in this study are conducive to cell adhesion and proliferation (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Research indicates that hyaluronan surfaces effectively mediate adhesion, spreading, proliferation, and directed differentiation of various cells (e.g., osteoblasts, mesenchymal stem cells) \u003csup\u003e[\u003cspan additionalcitationids=\"CR46 CR47\" citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]\u003c/sup\u003e. Consequently, HA plays a crucial role in inducing and guiding bone tissue regeneration. As a result, HA has become a core biomaterial in bone tissue engineering, widely applied in scenarios such as bone replacement fillers, bone repair scaffold matrices, or coating materials. It has been demonstrated that this substance provides dual structural and biochemical signaling support for the migration, growth, and new bone matrix deposition of bone cells. Moreover, a substantial body of in vitro and in vivo evidence consistently demonstrates that synthetic HA materials exhibit excellent biocompatibility, with no significant toxicity, non-sensitizing properties, and non-mutagenicity, along with favorable tissue integration. It has been demonstrated to form strong chemical bonds with host bone tissue and coexist harmoniously with blood components and surrounding soft tissues, thereby effectively reducing the risk of implant-related immune rejection. This provides an optimized biointerface and reliable regenerative healing environment for diverse clinical applications, including large-area bone defect repair, spinal/joint fusion, maxillofacial reconstruction, and orbital implants (e.g., prosthetic sockets). PCL is a synthetic polyester with excellent biocompatibility that has been approved by the U.S. Food and Drug Administration (FDA) for human medical applications. Its chemical inertness prevents it from triggering severe immune reactions or toxic effects when in contact with biological tissues\u003csup\u003e[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]\u003c/sup\u003e, and its ability to promote cell adhesion and proliferation is comparable to that of human amniotic membrane\u003csup\u003e[\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]\u003c/sup\u003e. The capacity to promote cell adhesion and proliferation is particularly evident in the corneal epithelium\u003csup\u003e[\u003cspan additionalcitationids=\"CR52 CR53\" citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]\u003c/sup\u003e, stroma\u003csup\u003e[\u003cspan additionalcitationids=\"CR56\" citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]\u003c/sup\u003e, and endothelium\u003csup\u003e[\u003cspan additionalcitationids=\"CR59\" citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e]\u003c/sup\u003e, further demonstrating the favorable biological effects of PCL on the ocular surface.\u003c/p\u003e\u003cp\u003eSecondly, the prepared scaffolds should exhibit a rough surface and a loose, porous structure at the microscopic level. The rough surface of the material in question has been shown to facilitate cell adhesion and proliferation on the scaffold, while the loose, porous structure of the material has been demonstrated to promote microvascular ingrowth into the scaffold. Collectively, these characteristics enhance the overall biocompatibility and tissue integration of the scaffold, thereby improving transplantation success rates. It is noteworthy that the two scaffolds with varying HA ratios, as discussed in this study, exhibited no substantial difference in porosity. Given the correlation between porosity and the preparation process, the present study focuses exclusively on the porosity data for the 70% HA content scaffold, as depicted in the SEM images. The surface roughness of the scaffolds in this study is clearly observable in the scanning electron micrograph (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). At 1200\u0026times; magnification, micro-pores between hydroxyapatite particles are directly visible. The porosity of the implant directly correlates with the extent of vascular ingrowth within the implant and the subsequent integration between the implant and the surrounding tissues. In most cases, pore volumes exceed 80%\u003csup\u003e[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e, \u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e]\u003c/sup\u003e. The following text is intended to provide a comprehensive overview of the subject matter. The HA/PCL scaffold in this study demonstrated a porosity of 91.66%, as indicated in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The structural characteristics of this material, namely its loose and porous nature, have been demonstrated to facilitate microvascular ingrowth into the voids, enhance tarsal tissue integration, and promote local metabolism. The pore size of the graft is also closely related to its vascularization and tissue integration. The porosity of grafts utilized for distinct tissues exhibits variability, with different pore sizes being optimal for specific applications. Despite the absence of a consensus on the optimal pore size for bone regeneration, the conclusions drawn are largely congruent. Pores measuring less than 100 \u0026micro;m have been shown to promote cell aggregation and cell-matrix interactions, thereby mimicking the dense ECM structure of natural cartilage\u003csup\u003e[\u003cspan additionalcitationids=\"CR64\" citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e]\u003c/sup\u003e. As S\u0026aacute;nchez-Salcedo et al\u003csup\u003e[\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e]\u003c/sup\u003e have observed, pore sizes ranging from 100 to 1000 \u0026micro;m have been shown to promote cell proliferation, bone tissue ingrowth, and the provision of mechanical strength. Additionally, research by Gupte et al\u003csup\u003e[\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e]\u003c/sup\u003e found that large pore sizes ranging from 400 to 625 \u0026micro;m in cartilage regeneration scaffolds facilitate vascular ingrowth and promote scaffold vascularization. In summary, smaller pore sizes (less than 100 \u0026micro;m) encourage cell adhesion and proliferation on the scaffold during transplantation. This facilitates ECM formation at the implantation site. Larger pore sizes (100\u0026ndash;1,000 \u0026micro;m) allow for vascular ingrowth into the scaffold, which promotes vascularization and enhances overall tissue integration. In this study, the HA/PCL scaffold's pore size characteristics were achieved through hierarchical regulation. Large pores (approximately 500 \u0026micro;m) were manually controlled, and small pores (\u0026lt;\u0026thinsp;50 \u0026micro;m) formed as natural voids through HA particle stacking after solvent evaporation. From a functional compatibility perspective, this structure theoretically ensures the cell adhesion efficiency necessary for tarsal plate repair and the capacity for angiogenesis. Ultimately, this promotes integration between the scaffold and the tissue of the tarsal plate.\u003c/p\u003e\u003cp\u003eMoreover, in the context of repairing eyelid defects using scaffold grafts, it is imperative that the scaffold adheres to the \"like-for-like\" principle\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. This principle stipulates that the replacement material must closely match the original state of the defective tissue in both structural characteristics and biological function. The eyelid is a specialized functional structure that is characterized by two distinctive structural features. Firstly, it possesses rigid support capacity and flexible deformation potential. This characteristic is primarily determined by the structure and mechanical properties of the internal tarsal plate. From a quantitative characterization perspective, the elastic modulus of the tarsal plate is the sole mechanical parameter that comprehensively reflects its rigid support effect and flexible deformation capacity. Sun et al\u003csup\u003e[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/sup\u003e obtained an average elastic modulus of 1.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61 MPa for human tarsal plates through measurements of fresh human tarsal tissue. The elastic modulus of the scaffold must be meticulously regulated within an optimal range. Insufficient control of this parameter can lead to two unfavorable outcomes: an excessively rigid material with inadequate deformation capacity, resulting in an inability to accommodate the flexible deformation requirements of the eyelid; or an excessively flexible material, which is incapable of providing the necessary rigid support function for tarsal plate repair. Furthermore, the scaffold with 70% HA content demonstrated higher fracture tensile strain and tensile strength (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), suggesting superior ductility and toughness. This phenomenon is primarily attributed to the enhanced plastic deformation capacity imparted by the relatively higher contents of PCL and PEG400. However, in the context of eyelid tarsal plate repair, the primary objective is not merely to achieve high strength or high elongation. The primary challenge lies in ascertaining whether the material can provide adequate static support while also meeting the dynamic flexibility demands of eyelid blinking movements. In summary, as the elastic modulus of the graft scaffold approaches that of the natural tarsal plate, the higher the mechanical compatibility between the scaffold and the plate, thereby better meeting the physiological and mechanical demands of the tarsal plate. For the two HA/PCL scaffolds with different ratios prepared in this study (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e), the 84% HA scaffold exhibited an elastic modulus of 2.66 MPa. This value is mechanically closer to the elastic modulus range of the tarsal plate, demonstrating superior alignment with the plate's inherent mechanical properties. Consequently, it is more likely to meet the mechanical compatibility requirements for tarsal plate reconstruction.\u003c/p\u003e\u003cp\u003eHA is a frequently utilized material in the regeneration of bone and cartilage. It demonstrates a low degradation rate in vivo\u003csup\u003e[\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e, \u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e]\u003c/sup\u003e and may persist for several years\u003csup\u003e[\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e]\u003c/sup\u003e. In vitro degradation studies by Navarrete-Segado et al\u003csup\u003e[\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e]\u003c/sup\u003e analyzed the behavior of HA scaffolds in 0.05 M TRIS buffer solution (initial pH 7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1) at 37\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u0026deg;C. Specifically, the pH exhibited a decline from 7.3 to 7.24 over a 72-hour period, with a variation of less than \u0026plusmn;\u0026thinsp;0.3, suggesting that scaffold degradation exerts minimal influence on the surrounding pH milieu. Scaffold weight loss exhibited a gradual increase with immersion time, reaching a mere 0.12% of total mass after 72 hours, indicative of minimal mass depletion. Concurrently, inductively coupled plasma atomic emission spectroscopy (ICP/AES) analysis revealed a low calcium ion release of 1.26 milligrams per liter over 72 hours. Collectively, these results confirm the slow degradation characteristics of this HA scaffold, providing experimental support for its application in small or non-load-bearing implant scenarios requiring gradual absorption. This approach is consistent with the established criteria for eyelid defect repair. Eyelid tissue is a thin-layered, non-load-bearing, delicate structure. The slow degradation characteristics of HA scaffolds precisely match the temporal progression of eyelid soft tissue regeneration. These cells provide a structural framework for the migration of cells and the deposition of the extracellular matrix over an extended period. Concurrently, the incremental release of calcium ions in low concentrations exerts a gentle modulatory effect on the local microenvironment, thereby promoting fibroblast activity and collagen synthesis without inducing mineral deposition or ectopic calcification risks. Moreover, eyelid repair generally entails scenarios involving small-scale, low-mechanical-load implantation, which does not necessitate the utilization of materials characterized by high strength or rapid degradation capabilities. Conversely, the phenomenon of gradual mass loss and ion release has been demonstrated to facilitate synchronized metabolic integration between the material and surrounding tissues. This approach prevents premature degradation-induced support failure or prolonged retention-induced chronic foreign body reactions, thereby jointly supporting the stable reconstruction of eyelid function and morphology at both structural and biological levels.\u003c/p\u003e\u003cp\u003eDespite the study's success in fabricating a flexible, conformable PEG400-plasticized HA/PCL composite scaffold through material modification and 3D printing technology, and its systematic characterization of physicochemical properties, several limitations persist. The present work is chiefly oriented towards material preparation and property characterization, with a conspicuous absence of cell compatibility evaluations or in vivo animal experiments. Consequently, the scaffold's in vivo degradation behavior, tissue integration capacity, and long-term repair efficacy remain to be assessed. This deficiency hinders a comprehensive understanding of the immune responses, vascularization processes, and functional restoration impacts the material may induce in real biological environments, such as eyelid defect models. Moreover, the dearth of in vivo experimental data impedes comprehensive analysis of the scaffold's mechanical property evolution and degradation/metabolism pathways within dynamic physiological environments. Future research should systematically conduct cell compatibility studies to confirm the biocompatibility of this scaffold material. Concurrently, the establishment of appropriate animal models (e.g., rabbit or rat eyelid defect models) is imperative to comprehensively evaluate the efficacy of the repair procedure across histological, biomechanical, and functional recovery dimensions. This will provide more robust experimental evidence for clinical translation. Building upon this foundation, comprehensive mechanical property optimization can be achieved by further refining the printing process (e.g., regulating fiber orientation), incorporating more efficient plasticizers, adjusting composite material ratios, or constructing finer multi-level composite structures. These approaches have been shown to enhance tensile strength and toughness while maintaining the material's optimal elastic modulus.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eThe present study successfully fabricated PEG400-plasticized HA/PCL composite scaffolds using pneumatic extrusion 3D printing technology. The physicochemical properties of the fabricated materials were systematically evaluated, and the potential of the materials as a replacement material for the posterior eyelid layer was determined. The findings suggest that the scaffold with 84% HA content demonstrates superior comprehensive properties: its elastic modulus of 2.66 MPa closely matches the natural mechanical properties of human tarsal plates (1.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61 MPa), concurrently meeting the mechanical demands of static support and dynamic blinking. The multi-level pore structure and high porosity provide an ideal microenvironment for cell adhesion, nutrient transport, and vascular ingrowth; the hydrophilic surface further enhances its biocompatibility. Furthermore, the gradual degradation profile of HA corresponds to the non-weight-bearing characteristics of the eyelid and its prolonged regeneration cycle, thereby enabling synchronized integration and reconstruction between the implant and host tissue. A comprehensive evaluation of the material's performance was conducted, which revealed that the 84% HA/PCL scaffold is more suitable for eyelid defect repair. Despite the notable advancements made in material design and performance characterization in this study, further validation of its biological properties and repair efficacy through cellular and animal experiments remains imperative. In summary, the PEG400-plasticized HA/PCL composite scaffold under consideration exhibits considerable promise as a tarsal plate replacement material for the eyelid. This potential is supported by its demonstrated mechanical adaptability, structural characteristics, and degradation behavior. These attributes provide substantial evidence to support the conduct of subsequent clinical translation studies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHydroxyapatite\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePCL\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePolycaprolactone\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eECM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eExtracellular Matrix\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePEG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePolyethylene Glycol\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSEM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eScanning Electron Microscopy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eDCM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDichloromethane\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTV\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTotal Volume\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSV\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSolid Volume\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSFD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eScaffold Density\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSolid Density\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePo\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePorosity\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the colleagues from the School of Optometry and the School of Advanced Manufacturing at Nanchang University for their insightful discussions and technical support. We are also grateful for the access to the experimental facilities provided by the Jiangxi Provincial Key Laboratory for Ophthalmology and the National Clinical Research Center for Ocular Diseases Jiangxi Province Division.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJincheng Liu and Simeng Lv: Contributed equally to this work as co-first authors; involved in methodology, investigation, and writing - original draft. Mengling Zhou, Mange Zhang, Qingyi Wang, Yangbin Fang, and Yao Lai: Participated in formal analysis, validation, and data curation. Fanrong Ai and Qin Huang: Served as co-corresponding authors; responsible for conceptualization, supervision, project administration, funding acquisition, and writing - review \u0026amp; editing. All authors have reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are available from the corresponding authors on reasonable request. The data supporting the findings of this research are not publicly available due to privacy or ethical restrictions but can be accessed for academic and non-commercial purposes upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Natural Science Foundation of Jiangxi Province (Grant No.20242BAB5490).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChang, E. 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Ceram.\u003c/em\u003e \u003cb\u003e9\u003c/b\u003e, 100235. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.oceram.2022.100235\u003c/span\u003e\u003cspan address=\"10.1016/j.oceram.2022.100235\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2022).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Eyelid reconstruction, 3D printing, Hydroxyapatite, Polycaprolactone, Biomechanical compatibility, Tissue engineering","lastPublishedDoi":"10.21203/rs.3.rs-7969055/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7969055/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eThis study developed extrusion-based 3D-printed PEG400-plasticized HA/PCL composite scaffolds for posterior lamellar eyelid reconstruction, optimizing material ratios to match native tarsal tissue properties.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eTwo scaffolds (70% vs 84% HA) were fabricated via pneumatic extrusion. Microstructure (SEM), porosity (Micro-CT), wettability (contact angle), and mechanical properties (tensile testing) were characterized. Statistical analysis used GraphPad Prism 8.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe 84% HA scaffold achieved an elastic modulus of ​2.66 MPa, closely aligning with native tarsal tissue (1.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61 MPa). Hierarchical pores (macropores: ~570.7 \u0026micro;m; micropores: ~20.81 \u0026micro;m) and high porosity (91.66%​) were observed. Both scaffolds showed hydrophilicity (contact angles: ​80.63\u0026deg;​ for 70% HA; ​77.97\u0026deg;​ for 84% HA). Though the 84% HA group had lower tensile strength, its biomechanical compatibility surpassed the 70% HA scaffold.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThe 84% HA/PCL scaffold exhibits optimal mechanical adaptation, porous architecture, and hydrophilicity for eyelid tarsal reconstruction. Its slow degradation profile supports clinical potential, pending in vitro cytocompatibility and in vivo validation.\u003c/p\u003e","manuscriptTitle":"Extrusion-based 3D Printing of PEG400-Plasticized HA/PCL Composite Scaffolds: A Study on Flexible Adaptation for Eyelid Defect Repair","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-10 19:13:38","doi":"10.21203/rs.3.rs-7969055/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b5f6d911-507f-4816-995b-13f43fdf028e","owner":[],"postedDate":"December 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":59274709,"name":"Biological sciences/Biotechnology"},{"id":59274710,"name":"Physical sciences/Engineering"},{"id":59274711,"name":"Physical sciences/Materials science"},{"id":59274712,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-12-17T12:24:28+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-10 19:13:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7969055","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7969055","identity":"rs-7969055","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}