Biocompatible Elastomeric Transistors for Implantable Bioelectronics

Biocompatible Elastomeric Transistors for Implantable Bioelectronics | 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 Biocompatible Elastomeric Transistors for Implantable Bioelectronics Jin Young Oh, Kyu Ho Jung, Jiyu Hyun, Yong Sung Koo, Min Woo Jeong, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4844804/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Sep, 2025 Read the published version in Nature Electronics → Version 1 posted You are reading this latest preprint version Abstract Implantable bioelectronics transforms the interface between electronics and biological systems, enabling continuous in situ monitoring and modulation of electrophysiological signals. A critical challenge remains in the mechanical mismatch between conventional rigid electronic components and soft biological tissues, which can lead to tissue damage and inflammation. Additionally, the low biocompatibility of existing soft electronic components exacerbates these issues. Here, we present biocompatible, elastomeric organic field-effect transistors (OFETs) designed for implantable applications. These OFETs utilize a blend of semiconducting nanofibers and medical-grade elastomers, such as poly[(dithiophene)-alt-(2,5-bis(2-octyldodecyl)-3,6-bis(thienyl)-diketopyrrolopyrrole)] (DPPT-TT) and bromo butyl rubber (BIIR), respectively. This composite film exhibits exceptional mechanical stretchability and biocompatibility with similar Young’s modulus with human tissues, maintaining high electrical performance even under 50% strain. In addition, the integration of biocompatible dual-layer Ag-Au metallization results in robust, stretchable, and corrosion-resistant electrodes. In vitro assessments with human dermal fibroblasts and macrophages confirmed the biocompatibility of the materials, showing no adverse effects on cell viability, proliferation, or migration. In vivo implantation studies in BALB/C mice revealed no significant inflammatory response or tissue damage, underscoring the potential for long-term biointegration. Our biocompatible and stretchable OFETs demonstrated stable operation in logic circuits, including inverters, NOR, and NAND gates under physiological conditions, offering a promising platform for various medical applications, from diagnostics to therapeutic interventions. Physical sciences/Materials science/Materials for devices/Electronic devices Biological sciences/Biotechnology/Nanobiotechnology/Bionanoelectronics Biological sciences/Immunology/Cell death and immune response Stretchable Implantable Biocompatible Organic Field-Effect Transistor E-skin Medical rubber Logic gate Bioelectronics Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Implantable bioelectronic devices are at the forefront of biomedical innovation, enabling continuous in situ monitoring and modulation of electrophysiological signals. 1 – 4 Traditional biomedical implants, such as pacemakers, neurostimulators, and insulin pumps, have predominantly relied on rigid inorganic materials like silicon-based semiconductors and metals. 5 , 6 While these materials have proven effective, their rigidity leads to significant mechanical mismatches with soft biological tissues, resulting in complications such as micro-injury, inflammation, fibrosis, and necrosis over time. 7 , 8 To address these limitations, recent research has shifted towards developing soft, lightweight, and stretchable bioelectronic devices that seamlessly integrate with human tissues. These devices typically consist of two primary components 2 , 3 , 9 – 11 : biointerface electrodes for signal acquisition and bioelectronic circuits for signal processing. Despite the considerable advancements in hydrogel-based electrodes, 12 – 15 creating stretchable transistors for bioelectronic circuits with high biocompatibility and stability in physiological environments remains a long-standing and critical challenge. Stretchable organic electrochemical transistors (sOECTs) were initially proposed for skin-like electronic circuits due to their low Young’s modulus and compatibility with biological ionic media. 16 However, sOECTs face several drawbacks for electronic circuit applications, including high off-currents and crosstalk due to their ion-based operation, which complicates the provision of individual inputs to an array of transistors. 17 – 19 Furthermore, the high charging currents at the channel/electrolyte interface of sOECTs pose risks of undesired neural activation in vivo. 20 Therefore, there is a pressing need to develop alternative devices to overcome these limitations. Stretchable organic field-effect transistors (sOFETs) are emerging as a promising alternative to sOECTs for high-frequency signal processing. 21 These devices leverage well-established field-effect transistor technologies while maintaining mechanical flexibility and preserving electrical performance, making them suitable for integration into bioelectronic circuits. 5 , 9 , 22 – 31 Despite their potential, most sOFETs have been fabricated using industrial-grade elastomers like SEBS, SBS, PU, and PDMS, which are not certified for biocompatibility and can induce chronic foreign body reactions. 10 Consequently, there is an urgent need for developing biocompatible and stretchable semiconductors for implantable electronics. Medical elastomers such as bromo butyl rubber (BIIR) have been specifically designed for biomedical applications, meeting stringent biocompatibility standards set by health authorities like ISO 10993 and the European Pharmacopoeia (EP). 32 – 34 These elastomers exhibit excellent mechanical properties, including shock absorption, low permeability, aging resistance, and high physical strength, alongside high chemical resistance and low reactivity with microorganisms. 35 – 38 These properties make BIIR ideal for blending with semiconductors to create stable, biocompatible, and stretchable transistors. This study introduces a new approach to fabricating skin-like implantable sOFETs using a cross-linked DPPT-TT and BIIR blend through vulcanization. This work represents the first application of BIIR as an elastomeric matrix for stretchable transistors, addressing the critical need for biocompatibility and mechanical compatibility in bioelectronics. The resulting transistors exhibit stable electrical performance under mechanical strain, maintaining functionality even at 50% elongation. Furthermore, we integrate the dual-layer metallization 39 of Ag and Au to create stretchable and biocompatible electrodes, ensuring robust performance in biofluid environments. Our comprehensive in vitro and in vivo evaluations confirm the biocompatibility and stability of these devices, showing no adverse effects on cell viability, proliferation, or migration and no significant inflammatory response or tissue damage in animal models. This work marks a significant advancement in developing biocompatible and stretchable OFETs and paves the way for their application in a wide range of bioelectronic circuits and implantable devices. The significance of our approach lies in combining a biocompatible elastomeric matrix with advanced semiconductor materials and innovative metallization techniques, providing a robust platform for next-generation implantable bioelectronics. This research addresses critical challenges in the field and opens new avenues for developing medical devices that can seamlessly integrate with human tissues, enhancing diagnostics and therapeutic interventions. Results and Discussion 1. Material design and vulcanization of implantable semiconductor Figure 1 a presents a schematic of a biocompatible and stretchable semiconductor film comprised of a semiconducting nanofiber network embedded within an elastomer matrix. This innovative design utilizes a molecular blend of a donor-acceptor-based semiconducting polymer with medical-grade rubber. Specifically, we used poly[(dithiophene)-alt-(2,5-bis(2-octyldodecyl)-3,6-bis(thienyl)-diketopyrrolopyrrole)] (DPPT-TT) as the polymer semiconductor and bromo isobutylene isoprene rubber (BIIR) as the biocompatible elastomer matrix. The blend film was chemically cross-linked through vulcanization, a well-established method to enhance the mechanical property of medical rubbers using additives such as sulfur (crosslinker), dipentamethylenethiuram tetrasulfide (DPTT, accelerator), and stearic acid (initiator) (Fig. 1 b). The phase separation forming the semiconducting nanofiber network results from the surface energy disparity between DPPT-TT and BIIR, enabling the formation of a highly interconnected DPPT-TT nanofiber network within the elastic BIIR matrix, thus imparting stretchability (Supplementary Fig. 2). 28 To determine the optimal blend ratio for electrical and mechanical properties, we evaluated the vulcanized semiconductor films across various weight ratios of DPPT-TT (1:9 to 9:1). The results showed stable field-effect mobility across ratios from 9:1 to 3:7, indicating that the semiconducting percolation path is preserved up to a 0.7 weight fraction of BIIR (Fig. 1 c, Supplementary Fig. 3). This ratio produced a highly elastic semiconducting film that sustained up to 100% strain without mechanical damage, as confirmed by optical microscopy (OM) images of the 3:7 blend film (Supplementary Fig. 4). Conversely, films with lower BIIR content (9:1 to 5:5) exhibited cracks at 25% strain, emphasizing the necessity of higher BIIR content for intrinsic stretchability (Supplementary Fig. 4). Therefore, the 3:7 DPPT-TT blend ratio was optimized for the field-effect mobility, crack-onset strain, and integrity of the semiconducting nanofiber network (Supplementary Figs. 5 and 6). To verify the vulcanization of BIIR in the blend film, we performed FT-IR analysis (Fig. 1 d, Supplementary Fig. 7). The vulcanization process involves three key stages: initiation for radical formation, propagation for crosslinking BIIR with sulfur and termination for end of the reaction. The reduction in the C-Br (667 cm − 1 ) peaks in the FT-IR spectra post-vulcanization confirmed the successful initiation (Fig. 1 d). The significant reduction in the C = C peak (1538 cm − 1 ) in neat BIIR post-vulcanization indicates successful propagation (Supplementary Fig. 7). 40 The blend film has difficulty decoupling the C = C peak of BIIR because DPPT-TT has a similar C = C peak, while the C = C peak was reduced in the neat BIIR film. The unchanged C = C peak of the blend film after the vulcanization indicates that the conjugated bond structure of DPPT-TT was preserved. The increased modulus observed in Derjaguin-Muller-Toporov (DMT) modulus mapping further confirmed vulcanization, enhancing the elasticity of the blend film while preserving its pristine nanomorphology (Fig. 1 e). Additionally, the unchanged UV-vis absorption spectra before and after vulcanization indicate that the vulcanization process selectively crosslinks BIIR chains without disrupting the conjugated molecular structure of DPPT-TT (Fig. 1 f, Supplementary Figs. 8 and 9). Transistors fabricated with vulcanized blend films exhibited higher mobility and on/off ratio, suggesting that vulcanization also serves as a thermal annealing process, optimizing the morphology of the semiconducting polymer film while crosslinking the BIIR elastomer (Fig. 1 i). We also performed X-ray photoelectron spectroscopy (XPS) depth profiling of the vulcanized blend film, which revealed a uniform distribution of S atoms from DPPT-TT nanofibers throughout the semiconductor film, facilitating effective charge injection and transport in both vertical and horizontal directions (Fig. 1 g). The dichroic ratio of the vulcanized blend film as a function of applied strain (0%-50%) showed a linear increase, indicating the alignment of semiconducting nanofibers along the strain direction without mechanical cracking (Fig. 1 h, Supplementary Fig. 10). Furthermore, atomic force microscopy (AFM) and conductive AFM (C-AFM) images showed a highly interconnected DPPT-TT nanofiber network aligned with the strain direction, providing a strain-insensitive conductive path (Fig. 1 j, k). This morphology was reflected in the stable electrical performance of the FETs, with negligible changes in mobility under strains from 0–100% on a rigid substrate (Fig. 1 l, Supplementary Figs. 11 and 12). Additionally, the mobility of the blend film remained consistent after 1000 stretching cycles at 100% strain, demonstrating excellent mechanical durability (Fig. 1 m, Supplementary Fig. 13). These results confirm that the vulcanized blend film is highly stretchable, with the nanostructure of DPPT-TT well-preserved under mechanical deformation. 2. Skin-like implantable active-matrix transistor To develop skin-like and biocompatible implantable transistors, we employed a dual-layer metallization technique using silver (Ag) and gold (Au) to create highly conductive, stretchable, and biocompatible electrodes. 39 , 41 Ag was selected for its excellent electrical contact properties, while Au provided robust protection against biofluid-induced corrosion, thereby enhancing the durability of the electrodes in vivo (Fig. 2 a, Supplementary Fig. 14). X-ray photoelectron spectroscopy (XPS) depth profiling confirmed an intermixing region of carbon and silver atoms, which enhances both stretchability and adhesion (Fig. 2 b). Initial resistance measurements demonstrated that the Ag-Au electrodes maintained low resistance after soaking in artificial sweat for 72 hr, indicating their superior corrosion resistance (Fig. 2 a). Transistors fabricated with Ag-Au dual-layer electrodes exhibited electrical performance comparable to those with pure Ag electrodes, with the added benefit of enhanced durability in biofluid environments (Fig. 2 c). The Ag-Au electrodes were stretchable up to 50% while maintaining a resistance of 10 2 Ω even after soaking in artificial sweat for 72 hr (Fig. 2 d, Supplementary Fig. 15)providing the viability for highly conductive, stretchable, and biocompatible electrodes in skin-like implantable transistors. Figure 2 e shows the typical transfer characteristics of a skin-like implantable transistor at various drain voltages, demonstrating its capability to operate under low voltage conditions essential for safe in vivo applications (Supplementary Fig. 18). The transistors maintained stable electrical performance and mechanical durability, retaining their initial field-effect mobility and on/off ratios up to 50% strain, even after 10,000 stretching cycles (Fig. 2 f, g, Supplementary Fig. 19–22). This robustness was further validated by negligible changes in drain current after 72 hr of soaking in various artificial sweat solutions (Fig. 2 h, Supplementary Fig. 23), highlighting the effectiveness of Ag-Au dual-layer metallization in creating resilient and reliable electrodes for stretchable transistors. To further validate the practical applicability of our devices in circuits, we fabricated a 5×5 active-matrix array of skin-like implantable transistors. The array demonstrated uniform field-effect mobility and drain current across all devices, confirming its high yield and suitability for bioelectronic applications (Fig. 2 j, k). The field-effect mobility of the active-matrix array showed consistent performance, with minimal variation in on-current and mobility under different uniaxial strains (Fig. 2 l, Supplementary Fig. 24). 3. In vitro biocompatibility tests for skin-like implantable transistors In vitro biocompatibility tests were conducted using human dermal fibroblasts (hDFs) and macrophages (Mφ) to evaluate the safety and effectiveness of the materials used in the implantable semiconductor and transistor. The tests assessed the impact of each material—BIIR, SEBS, blend film, and fully assembled transistor—on cell viability, migration, and gene expression. A schematic overview of the in vitro experiment is shown in Fig. 3 a. Live/dead assays and CCK-8 assays were used to assess the cell viability. Fluorescence microscopy results from the live/dead assay showed green signals for live cells and red signals (with white arrows) for dead cells, with minimal red signals observed across all material groups, confirming high cell viability (Fig. 3 b). CCK-8 assay results further supported these findings, showing no significant differences in cell viability among the groups (Fig. 3 c). These results indicate that all materials used in the implantable semiconductor and transistor have prominent biocompatibility. The effect of each material on cell migration was investigated using an in vitro wound closure assay with hDFs. Similar wound closure rates across all groups indicated that the materials did not impair the migration properties of hDFs (Fig. 3 d, e, Supplementary Fig. 25). Gene expression analysis using qRT-PCR revealed no significant differences in the expression of proliferation-related genes (PCNA and Ki67) and apoptosis-related genes (BAX and BCL-2) among the groups, except for a substantial increase in CXCR4 expression in the blend film group. This increase suggests the enhanced migration property of hDFs in the presence of the blend film (Fig. 3 f). Inflammatory potential was assessed by profiling gene expression in macrophages (Mφ, Raw264.7 cells). After co-culturing Mφ with each material, the expression of specific markers for pro-inflammatory (M1) macrophages was measured. BIIR induced the lowest level of CD86 expression. At the same time, other groups showed similar levels (Fig. 3 g). The blend film and BIIR groups exhibited balanced profiles in CD80, STAT1, and iNOS expression compared to the control. In contrast, the SEBS group showed the highest gene expression level, indicating a higher propensity for inducing inflammation. The antibacterial properties of the materials were evaluated using genetically modified strains of Escherichia Coli (E. Coli) and Staphylococcus Aureus (S. Aureus) expressing green fluorescent protein (GFP). The positive control group (gelatin-coated glass coverslip) showed significantly higher bacterial growth, while the BIIR, SEBS, blend film, and transistor groups exhibited no significant differences in bacterial numbers, indicating effective anti-bacterial properties (Fig. 3 h, i). Representative fluorescence images confirmed lower bacterial viability on the blend film than bare PDMS (Fig. 3 j). These results indicate an enhanced anti-bacterial effect of the fabricated DPPT-TT: BIIR, suggesting their potential application in medical devices. In vitro tests demonstrated that the DPPT-TT blend and the fully assembled transistors are highly biocompatible, supporting cell viability, proliferation, and migration without inducing significant inflammatory responses. 4. In vivo biocompatibility tests for skin-like implantable transistor To evaluate the in vivo biocompatibility of our blend film, a comprehensive set of tests was conducted using a subcutaneous implant model in BALB/C mouse (Fig. 4 a). These tests aimed to assess the inflammatory response, tissue integration, and overall compatibility of the materials over a prolonged period. Hierarchical clustering heatmap analysis revealed no significant differences between the sham and implanted groups (Fig. 4 b). Principal component analysis (PCA) was performed on genetic data involving 19 genes per group. Five principal components were identified, with PC1 accounting for 46.54% (eigenvalue: 8.843) and PC2 for 35.06% (eigenvalue: 6.660) of the variance. IL-10 and iNOS (positive direction) and IL-6 (negative direction) significantly influenced PC1, while IL-1β (positive direction) and K-14 (negative direction) markedly influenced PC2 (Fig. 4 c). The distribution of PC scores for sham and implanted groups showed no significant differences, demonstrating the materials’ compatibility with biological tissues and potential for long-term implantation (Fig. 4 d). Macrophage phenotyping confirmed the absence of significant inflammatory responses. Western blot analysis of macrophage markers showed similar levels of M1 and M2 macrophage marker expression in both sham and implanted groups, indicating that no severe inflammation was observed, which is essential for maintaining tissue homeostasis (Fig. 4 e and Supplementary Fig. 26). Histological analysis using hematoxylin and eosin (H&E) staining provided additional evidence of biocompatibility. Tissue sections around the implants displayed normal collagen layer formation and no significant differences in tissue architecture compared to control groups 30 days after the implantation (Fig. 4 f). This suggests that the materials integrate well with the host tissue without causing adverse reactions. Immunohistochemistry for M1 and M2 macrophage markers further supported these findings. Sections stained for iNOS (M1 marker), CD163 (M2 marker), and CD68 (Mφ marker) showed no significant differences between the sham and implanted groups, confirming that the blend film implantation did not provoke an inflammatory response (Fig. 4 g). 5. Skin-like implantable circuits for bioelectronics To demonstrate the practical application of our skin-like implantable transistors in bioelectronic devices, we developed and tested various logic circuits, including inverters, NOR, and NAND gates, in vivo (Supplementary Fig. 27). These circuits are essential components for complex bioelectronic systems, enabling advanced signal processing capabilities within the human body. Figure 5 a provides a schematic overview of the subcutaneous implantation of logic circuits fabricated with skin-like implantable transistors. These circuits were designed to maintain stable electrical performance under mechanical strain and physiological conditions. Pseudo-CMOS design-based inverter, NOR, and NAND circuits (Fig. 5 b, f, and h) were fabricated for the versatility of our approach. To validate the functionality of our logic circuits in vivo , we implanted the devices into BALB/C mice and monitored their performance over 3 days. The inverter circuits, fundamental building blocks for digital logic, showed stable voltage transfer characteristics (VTCs) with apparent switching behavior under 50% strain (Fig. 5 d). The gain of the inverters remained consistent, even after implantation and stretching, underscoring their mechanical robustness and stability in a biological environment (Fig. 5 e). This performance is crucial for accurate signal processing in bioelectronic applications. The NOR and NAND gates maintained their logical output states under the same conditions, demonstrating robust performance despite mechanical deformation (Fig. 5 j, k and (Supplementary Fig. 28–31). The ability of these logic gates to function correctly under strain is vital for developing reliable and flexible bioelectronic circuits. The NAND and NOR gate retained stable electrical characteristics, including consistent output voltages, throughout the implantation period (Fig. 5 h). This long-term stability in a physiological environment highlights the suitability of our devices for real-world bioelectronic applications. In vivo biocompatibility was assessed by analyzing inflammation markers and histology. Figure 5 l and Supplementary Fig. 32 present quantitative data and representative images of western blot bands for M1 and M2 macrophage markers and inflammation-related markers. All markers, except CD163, showed similar results to the sham group, indicating no significant inflammation with the logic device implantation, comparable to the sham group. Short-term (3 days) implantation showed no immune cell infiltration at the implanted site in either group (Fig. 5 m). This suggests that our semiconductor-based circuits are suitable for implantable electronics and can function effectively within a biological environment. Conclusion We have developed biocompatible elastomeric organic field-effect transistors (OFETs) using a vulcanized blend film of semiconducting polymer nanofiber and medical-grade elastomer. These transistors exhibit remarkable mechanical flexibility and maintain stable electrical performance under significant strain, up to 100%. Integrating Ag-Au dual-layer metallization for the electrodes ensures excellent electrical contact and resistance to biofluid-induced corrosion. Our comprehensive in vitro biocompatibility assessments with human dermal fibroblasts and macrophages confirmed that the DPPT-TT blend does not negatively impact cell viability, proliferation, and migration or cause inflammation and exhibits superior anti-bacterial properties. An in vivo study using a subcutaneous implant model in BALB/C mice demonstrated no significant inflammatory response or tissue damage, confirming the materials’ suitability for long-term implantation. Furthermore, the fabricated skin-like implantable transistors and logic circuits, including active-matrix arrays, inverters, NOR, and NAND gates, maintained their functionality under mechanical stress and physiological conditions. These findings underscore the potential of these biocompatible and stretchable OFETs for a wide range of bioelectronic applications, offering a promising platform for advanced medical devices aimed at seamless integration with biological tissues. 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Sci. adv. 8.51,eade2988 (2022). Chumnum, K., Kalkornsurapranee, E., Johns, J., Sengloyluan, K. & Nakaramontri, Y. Combination of self-healing butyl rubber and natural rubber composites for improving the stability. Polymers (Basel) 13, 1–22 (2021). Chae, S. et al. Kinetically controlled metal-elastomer nanophases for environmentally resilient stretchable electronics. Nat Commun 15, (2024). Li, G. et al. Fabricating Composite Cell Sheets for Wound Healing: Cell Sheets Based on the Communication Between BMSCs and HFSCs Facilitate Full-Thickness Cutaneous Wound Healing. Tissue Eng Regen Med 21, 421–435 (2024). Materials and Methods Materials Au (99.99%, 3 mm granules) was purchased from SYSCIENCE (Seoul, Republic of Korea). Ag (99.99%, 3–5mm granule) was purchased from SYSCIENCE. Poly[(dithiophene)-alternate-(2,5-bis(2-octyldodecyl)-3,6-bis(thienyl)-diketopyrrolopyrrole)] (DPPT-TT) was purchased from Derthon (Shenzhen, China). Bromo butyl rubber (BIIR) was provided by Samsung Medical Rubber. SEBS H 1062 and SEBS H 1052 were provided by Asahi KASEI. H1062 (S/EB weight ratio, 18/82) and H1052 (S/EB weight ratio, 20/80) were used as the elastic substrate and dielectric layer, respectively. Anhydrous toluene (99.8%), anhydrous chlorobenzene (99.8%), anhydrous chloroform (99.8%), sulfur, dipentamethylenethiuram tetrasulfide, trichloro(octadecyl)silane (OTS), and stearic acid were purchased from Sigma–Aldrich (St. Louis, Missouri, MO, USA). Poly(dimethylsiloxane) (PDMS, Sylgard 184) and the curing agent were purchased from Dow Corning (Midland, MI, USA). The PDMS was cured at a ratio of 11:1 (base/curing agent, w/w) at 55 ℃ overnight for the stamp. Silicon wafer (SiO 2 /Si, , 1–30 Ω, 300 nm SiO 2 ) was purchased from iTASCO. All the chemicals were used as received without further purification. Device fabrication Organic thin film transistor on rigid substrate The solution for the semiconductor was prepared by dissolving 0.8 wt% of DPPT-TT, BIIR, and cross-linker at various blending ratios in anhydrous chlorobenzene at 120 °C for 4 h. BIIR, sulfur, DPTT, and stearic acid were added in a ratio of 100:1:1:5 and used as the elastic matrix of the semiconducting films. The solutions for the semiconductor were spun on an OTS-treated SiO 2 /Si wafer at 800 rpm for 1 min after filtration with a PTFE-D (0.2 μm) filter. The semiconducting film was annealed at 150 °C for 1 h. All processes were performed under a N 2 atmosphere in a glove box (H 2 O < 0.01 parts per million (ppm) and O 2 < 0.01 ppm). The dielectric solution was prepared by dissolving 60 mg/mL of SEBS H1052 in toluene at 60 °C for 4 h. The dielectric solution was spun at 1000 rpm for 1 min on an indium tin oxide (ITO; sheet resistance, 20 ohm/square) glass substrate. The semiconducting film was transferred from an OTS-treated wafer onto an SEBS/ITO glass substrate using PDMS stamps. The Ag source/drain electrodes were evaporated at 0.2 nm/s using a thermal evaporator. The channel length and width were 1000 and 150 μm, respectively. Fully stretchable transistors The elastic substrates for the fully stretchable transistor were prepared by casting SEBS H1062 (100 mg/ml in toluene) onto glass slides. After drying overnight, the Au (30 nm)/Ag gate electrode (30 nm) was evaporated onto an SEBS substrate at 0.2 nm/s under high vacuum (below 5.0 × 10-6 torr). The SEBS H1052 dielectric and semiconducting film (3:7 ratio of DPPT-TT to BIIR) were continuously transferred onto the gate electrode. Au/Ag source/drain electrodes (30 nm each) were evaporated onto semiconducting films at a speed of 0.05 nm/s. The channel length and width were 1000 and 150 μm, respectively. For active-matrix transistor array All procedures for the fabrication of the active-matrix transistor array were identical to those for the fabrication of fully stretchable transistors, except for the dielectric film, which was designed using a different concentration (75 mg/ml in toluene, spin-coated at 1000 rpm for 1 min) to obtain a thicker dielectric film (1.9 μm). The channel length and width were 2000 and 150 μm, respectively. For logic gate devices including inverter, NAND, and NOR The SEBS substrate, semiconducting thin film, and dielectric layer were prepared using the same process as that for the fully stretchable active-matrix transistor array. The bottom Au (30 nm)/Ag electrodes (30 nm) were evaporated onto the SEBS H1062 substrates designed for each logic gate. The semiconducting films and dielectric layers were sequentially transferred onto the Ag electrode. Finally, the top Au (30 nm)/Ag electrodes (30 nm) were thermally evaporated using a designed pattern. Stretchable and biocompatible encapsulation layer The encapsulation films were prepared by casting the BIIR solution (120 mg/ml in chlorobenzene) on a TeflonTM mold, which was dried for 2 d and annealed at 150 °C for 30 min. The encapsulation films were applied to both sides (top and bottom) of the stretchable device. Characterization The devices were stabilized by aging them overnight in an autodry desiccator (24% humidity, 27 ˚C). The electrical characteristics of the devices were measured using a probe station connected to a KEITHLEY 4200 under atmospheric conditions, and a vacuum probe station with a Peltier device was connected to a KEITHLEY 2636B to control the temperature. The dielectric capacitance was measured using a probe station connected to an LCR meter (Keysight 4274A). UV-Vis-NIR spectroscopy was performed using a Jasco V-770. The surface structure was observed using atomic force microscopy (AFM; Bruker MultiMode 8-HR) under ambient conditions. Optical microscopy (OM) images were acquired using a Leica 2DM4 M. The film thickness was measured using an ellipsometer (WONWOO STRC-2000). To obtain stretched OM and AFM images, the semiconductor was transferred using the PDMS stamp method. Cell culture hDFs were purchased from Lonza (Basel, Switzerland). The hDFs were cultured in Dulbecco's modified Eagle's medium (DMEM; Gibco BRL, Gaithersburg, Maryland, USA) supplemented with 10% (v/v) fetal bovine serum (FBS; Gibco BRL) and 1% (v/v) penicillin/streptomycin (PS; Gibco BRL). The cells were incubated at 37 °C with 5% CO 2 saturation. The cell culture medium was changed every 2 d. Cells within eight passages were used for the experiments. Raw 264.7 cells were cultured in DMEM (Gibco BRL) supplemented with 10% (v/v) FBS and 1% (v/v) PS. FDA/EB staining assay Fluorescein diacetate (FDA, Sigma–Aldrich) and ethidium bromide (EB, Sigma–Aldrich) were used for fluorescein diacetate/ethidium bromide staining. FDA (green) stains the cytoplasm of viable cells, whereas EB (red) stains the nuclei of non-viable cells. The staining solution was freshly prepared by combining 10 mL of FDA stock solution (1.5 mg/mL FDA in dimethyl sulfoxide), 5 mL of EB stock solution (1 mg/mL EB in phosphate-buffered saline, PBS), and 3 mL of PBS. hDFs were then incubated in the staining solution for 3 min at 37 °C. After staining, the samples were washed twice with PBS and examined under a fluorescence microscope (DFC 3000 G; Leica, Wetzlar, Germany). Cell viability Cell proliferation was analyzed using the Cell Counting Kit-8 (CCK-8; Sigma–Aldrich) assay. The hDFs were seeded in 24-well plates (2 × 10 4 cells/well), and CCK-8 was used to measure cell proliferation for 1 d after co-culturing with each material using Transwell. The cells were washed in PBS, and the medium was replaced with a culture medium containing a CCK-8 solution (10%, v/v). After 2 h of incubation at 37 °C, the absorbance of each well was measured at 450 nm (Infinite F50; TECAN, Männedorf, Switzerland). In vitro wound closure The hDFs were grown in confluence in 6-well plates 42 and then replenished with DMEM (Gibco BRL). Thereafter, the cells were co-cultured sequentially using BIIR, SEBS, DPPT:TT:BIIR, and logic devices for 1 d. A straight scratch was made on the hDF layer using a P1000 pipette tip. After incubation for 24 h, the gap width of the scratch following repopulation was measured and compared with the initial gap size at 0 h. The size of the denuded area was determined at each time point from the digital images using Adobe Photoshop CC (Adobe Systems, CA, USA). Real-time polymerase chain reaction (qRT-PCR) The relative gene expression levels of human BCL-2, BAX, CXCR-4, PCNA, Ki67, and mouse CD80, CD86, iNOS1, iNOS2, and STAT1 were quantified by performing qRT-PCR . Human-specific gene primers were utilized for in vitro hDF analysis. Mouse gene primers were used for in vivo skin tissue analysis. The total ribonucleic acid (RNA) was extracted from the samples using 1 mL of Trizol reagent (Life Technologies, Inc., Carlsbad, CA, USA) and 200 μL of chloroform. The lysed samples were centrifuged at 12,000 rpm for 10 min at 4 °C. The RNA pellet was then washed with 75% (v/v) ethanol in water and dried. Subsequently, the samples were dissolved in RNase-free water. For qRT-PCR, the SsoAdvanced™ Universal SYBR Green Supermix kit (Bio-Rad, Hercules, CA, USA) and CFX Connect™ real-time PCR detection system (Bio-Rad) were used. Table 1 lists the primers used for qRT-PCR. Table 1. Sequences of the qRT-PCR primer. Primers Sequences Human GAPDH F : 5′-GTCGGAGTCAACGGATTTGG-3′ R : 5′-GGGTGGAATCATTGGAACAT-3′ Human BCL-2 F : 5′-CAACATCGCCCTGTGGATGA-3′ R : 5′-GGGCCAAACTGAGCAGAGTC-3 Human BAX F : 5′-GCAACTTCAACTGGGGCCGGG-3′ R : 5′-GATCCAGCCCAACAGCCGCTC-3′ Human CXCR-4 F : 5′-TAC ACC GAG GAA ATG GGC TCA-3′ R : 5′-AGA TGA TGG AGT AGA TGG TGG G-3′ Human PCNA F : 5′-AGG GCT GAA GAT AAT GCT GAT ACC-3′ R : 5′-CTC CTG TTC TGG GAT TCC AAG TTG-3′ Human Ki67 F : 5′-TGACCCTGATGAGAAAGCTCAA-3′ R : 5′-CCCTGAGCAACACTGTCTTTT-3′ Mouse CD80 F : 5′-AGTTTCTCTTTTTCAGGTTGTGAA-3′ R : 5′-ACATGATGGGGAAAGCCAGG-3′ Mouse CD86 F : 5′-CTTACGGAAGCACCCACGAT-3′ R : 5′-CGGCAGATATGCAGTCCCAT-3′ Mouse iNOS F : 5′- CTGGGAGCGCTCTAGTGAAG-3′ R : 5′- CTCTCCACTGCCCCAGTTTT-3′ Mouse STAT1 F : 5′-GATCGCTTGCCCAACTCTTG-3′ R : 5′-ACTGTGACATCCTTGGGCTG-3′ Anti-bacterial test The antibacterial test was conducted using two representative bacterial strains commonly associated with infections on medical devices: Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In this study, we used the genetically modified E. coli C2925 and S. aureus NCTC 8325-4 strains to express the green fluorescent protein (GFP). Both bacterial stains were cultured in a tryptic soy broth medium with ampicillin (100 μg/ml) and chloramphenicol (10 μg/ml) at 37 ℃ for 24 h, until an OD600 of 108 CFUs/mL was reached in fresh media. Each strain was applied to a film sample (n = 6) prepared in a 24-well plate at a concentration of 5 × 10 7 CFU/ml per well. Gelatin (0.1% w/w)-coated glass coverslips promoting bacterial adhesion and growth served as positive controls along with bare PDMS blocks. After incubating at 37 ℃ for 24 h, non-adhered bacteria were removed by washing three times with PBS, and the bacterial colonies were fixed with a 4% paraformaldehyde (PFA) solution for 10 min, followed by two washes with PBS. The bacteria were imaged using confocal microscopy (LSM800, Carl Zeiss AG, Germany) at 40X magnification at the BT Research Facility Center, Chung-Ang University. The z-stack images were processed using the maximum projection method, and the fluorescence intensity was measured using ImageJ (NIH, Bethesda, MD, USA) to quantify the relative number of bacteria adhered to each sample. In vivo subcutaneous DPPT-TT:BIIR and logic device implantation Six-week-old female Balb/C mice (20–25 g body weight; Orient, Seoul, Republic of Korea) were anesthetized using 200 μL of xylazine (20 mg/kg) and ketamine (100 mg/kg) diluted in normal saline solution. Hair was removed from the right side of the back using a combination of animal electric clippers and nair (less than 1 min). The implanted site was marked with a 10 × 10 mm 2 stamp on the lateral flank of each mouse. The epidermis, dermis, and stratum corneum were surgically excised at the top and right sides. The skin was opened by flipping. For the DPPT-TT:BIIR (D:B) and logic device groups, each material was carefully implanted into the open area. An identical surgical procedure was performed for the sham group without implantation. After 3 and 30 d, the subcutaneously implanted mice were sacrificed for in vivo analysis. All the animals were cared for in accordance with the Guidelines for the Care and Use of Laboratory Animals of Sungkyunkwan University (SKKUIACUC2022-04-40-1). Western blotting The retrieved tissues were sectioned and lysed in RIPA buffer (Rockland Immunochemicals, Inc., Limerick, PA, USA). After centrifugation at 10,000 g for 10 min, the supernatant was prepared as a protein extract. Protein concentrations were determined using a BCA assay (Pierce Biotechnology, Rockford, IL, USA). Equal amounts of protein from each sample were mixed with the sample buffer and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) using a 10% (v/v) resolving gel. The separated proteins were transferred to immune-blot PVDF membranes (Bio-Rad). The membranes were blocked with 5% (w/v) skim milk in Tris-buffered saline (TBS-T; 50 mM Tris–HCl (pH 7.5), 150 mM NaCl, 2.5 mM KCl) and incubated for 1 h at 25 °C. Then, the membranes were probed overnight at 4 °C with antibodies against glyceraldehyde 3-phosphate dehydrogenase (GAPDH) (Abcam, ab9485, Cambridge, UK), CD163 (Abcam, ab182422), CD206 (Abcam, ab64693), STAT1 (Cell Signaling Technology, CS9172), STAT6 (Cell Signaling Technology, CS9362), and TGF-β (Cell Signaling Technology, CS3711). Thereafter, the membranes were incubated in horseradish peroxidase-conjugated secondary antibodies (R&D Systems, HAF008 for GAPDH, HAF017 for CD163, CD206, STAT1, STAT6, and TGF-β, Minneapolis, MN, USA) for 1 h at 25 °C, followed by the addition of an ECL reagent (TransLab, Daejeon, Republic of Korea). The blots were developed in a dark room, and luminescence was recorded using an X-ray blue film (Agfa HealthCare NV, Mortsel, Belgium). Histology Impaired skin tissue specimens retrieved 3 d post-treatment were fixed with a 4% PFA solution and embedded at an optimum cutting temperature (OCT) compound (SciGen Scientific, Gardenas, USA). Thereafter, 10 μm sections obtained from the specimens were stained with hematoxylin and eosin (H&E) to assess re-epithelialization. Immunohistochemistry For immunohistochemical staining, the samples embedded in OCT compound were cut into 10 μm-thick sections at −22 °C. To stain the pro-inflammatory macrophages, the sections were immunofluorescence-stained with antibodies against INOS (Abcam, ab178945) and CD68 (Abcam, ab955). To stain anti-inflammatory macrophages, the sections were immunofluorescence-stained with antibodies against CD163 (Abcam, ab182422) and CD68 (Abcam, ab955). INOS and CD163 signals were visualized using fluorescein isothiocyanate-conjugated secondary antibodies (Jackson ImmunoResearch Laboratories, West Grove, PA, USA). The CD68 signal was visualized using rhodamine (TRITC)-AffiniPure goat anti-mouse IgG (Jackson ImmunoResearch Laboratories). The sections were counterstained with DAPI and examined via fluorescence microscopy (DFC 3000 G, Leica). Additional Declarations There is NO Competing Interest. Supplementary Files 20240801SupportingInformation.docx Cite Share Download PDF Status: Published Journal Publication published 02 Sep, 2025 Read the published version in Nature Electronics → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4844804","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":346522410,"identity":"8890a17d-4f8f-475a-83c8-eb5b0f48e680","order_by":0,"name":"Jin Young Oh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAq0lEQVRIiWNgGAWjYBACxgYGNoYPBw7AOERqYZxBkhYgYGPmIUkL84zkY49tztxJbGA//IBx5h5iHDYjLd0458azxAaeNAPGDc+I0pJjJp3z4XBiA0MOA+ODA8RqsQBp4X9DihaGG0AtEkBbNhClpedZmmTPmcPGbRLPDA7OIEaLYXvyMYkfxw7L9vMnP3zYQ5SWCQkQBhsQE6OBgUGenzh1o2AUjIJRMJIBAChPPmnww5LmAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-2260-9960","institution":"Kyung Hee University","correspondingAuthor":true,"prefix":"","firstName":"Jin","middleName":"Young","lastName":"Oh","suffix":""},{"id":346522411,"identity":"215b548f-8e05-4d3e-adf1-4ce17e00d3f4","order_by":1,"name":"Kyu Ho Jung","email":"","orcid":"","institution":"Kyung Hee University","correspondingAuthor":false,"prefix":"","firstName":"Kyu","middleName":"Ho","lastName":"Jung","suffix":""},{"id":346522412,"identity":"06a895e8-bf7a-4638-8256-f8e9fcf22de7","order_by":2,"name":"Jiyu Hyun","email":"","orcid":"","institution":"Sungkyunkwan University","correspondingAuthor":false,"prefix":"","firstName":"Jiyu","middleName":"","lastName":"Hyun","suffix":""},{"id":346522413,"identity":"b0e8de9c-2d2b-48e7-91e2-b469fd034035","order_by":3,"name":"Yong Sung Koo","email":"","orcid":"","institution":"JooAm Co","correspondingAuthor":false,"prefix":"","firstName":"Yong","middleName":"Sung","lastName":"Koo","suffix":""},{"id":346522414,"identity":"66fee631-6bde-4700-ab57-e46ea19781fa","order_by":4,"name":"Min Woo Jeong","email":"","orcid":"","institution":"Kyung Hee University","correspondingAuthor":false,"prefix":"","firstName":"Min","middleName":"Woo","lastName":"Jeong","suffix":""},{"id":346522415,"identity":"94b77171-67e5-4f4c-adb8-3822600d77bd","order_by":5,"name":"Tea Uk Nam","email":"","orcid":"","institution":"Kyung Hee University","correspondingAuthor":false,"prefix":"","firstName":"Tea","middleName":"Uk","lastName":"Nam","suffix":""},{"id":346522416,"identity":"40618092-f25a-40b5-a5e0-21054cffe5ce","order_by":6,"name":"Ngoc Thanh Phuong Vo","email":"","orcid":"","institution":"Kyung Hee University","correspondingAuthor":false,"prefix":"","firstName":"Ngoc","middleName":"Thanh Phuong","lastName":"Vo","suffix":""},{"id":346522417,"identity":"f35cf75b-e78c-4107-bfd4-b7e74e1e9178","order_by":7,"name":"Jiseon An","email":"","orcid":"","institution":"Sungkyunkwan University","correspondingAuthor":false,"prefix":"","firstName":"Jiseon","middleName":"","lastName":"An","suffix":""},{"id":346522418,"identity":"827cae20-d6a2-4466-80fc-3bd4b2f43945","order_by":8,"name":"Juan Yang","email":"","orcid":"","institution":"Chung-Ang University","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"","lastName":"Yang","suffix":""},{"id":346522419,"identity":"454fb035-8d95-49ab-bc37-5dffa4b2a27f","order_by":9,"name":"Suk Ho Bhang","email":"","orcid":"","institution":"Sungkyunkwan University","correspondingAuthor":false,"prefix":"","firstName":"Suk","middleName":"Ho","lastName":"Bhang","suffix":""},{"id":346522420,"identity":"4b00022b-92ab-4932-bf9c-ad66f45679c5","order_by":10,"name":"Jeong-Kee Yoon","email":"","orcid":"","institution":"Chung-Ang University","correspondingAuthor":false,"prefix":"","firstName":"Jeong-Kee","middleName":"","lastName":"Yoon","suffix":""}],"badges":[],"createdAt":"2024-08-02 00:35:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4844804/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4844804/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41928-025-01444-9","type":"published","date":"2025-09-02T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":64064504,"identity":"96f841c1-4bdf-4072-9d8b-3e6eead7c4fd","added_by":"auto","created_at":"2024-09-06 03:31:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":6647034,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMaterial design and vulcanization of implantable semiconductor.\u003c/strong\u003e \u003cstrong\u003ea.\u003c/strong\u003eSchematic of blending film and \u003cstrong\u003eb.\u003c/strong\u003e vulcanization for implantable semiconductors. Chemical structures showing the semiconducting polymer (DPPT-TT), medical rubber (BIIR), and crosslinker (sulfur). \u003cstrong\u003ec\u003c/strong\u003e. Changes in mobility as a function of weight ratios (DPPT-TT: BIIR). \u003cstrong\u003ed.\u003c/strong\u003e FTIR spectra of the pristine and crosslinked blend films\u003cstrong\u003e e.\u003c/strong\u003e DMT modulus mapping images of the pristine (left) and crosslinked blend film (right).\u003cstrong\u003e f.\u003c/strong\u003e Normalized UV-Vis absorbance spectra (left) and mobility (right) of the pristine and crosslinked blend films. \u003cstrong\u003eg.\u003c/strong\u003e XPS depth profiling of blend film. \u003cstrong\u003eh.\u003c/strong\u003eDichroic ratio of the blend film ranging from 0 to 50% uniaxial strain. \u003cstrong\u003ei.\u003c/strong\u003eTransfer (left) and output (right) characteristics of optimized blending weight ratio (3:7). \u003cstrong\u003ej.\u003c/strong\u003e AFM phase image and \u003cstrong\u003ek.\u003c/strong\u003e C-AFM image of the blend film with 0 and 50% strain \u003cstrong\u003el\u003c/strong\u003e. Mobilities of blend film ranging from 0 to 50% uniaxially stretched and released states. \u003cstrong\u003em.\u003c/strong\u003e Mobilities of blend film under multiple stretching cycles with 100% uniaxial strain.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-4844804/v1/f9432187ccf862b3da695fb5.png"},{"id":64064503,"identity":"24191079-6848-42ba-a2cb-16341d9fafe5","added_by":"auto","created_at":"2024-09-06 03:31:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2538204,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSkin-like implantable active-matrix transistor.\u003c/strong\u003e \u003cstrong\u003ea.\u003c/strong\u003e Transfer characteristics of blend film with different source and drain electrodes (Ag, Au, Ag/Au). \u003cstrong\u003ea\u003c/strong\u003e. OM images (top) of the Ag, Au, and Ag/Au electrode on blend film after soaking in PBS (72 hrs) and resistance change of Ag/Au electrode on blend film (bottom).\u003cstrong\u003e b.\u003c/strong\u003e XPS depth profiling of Ag/Au electrode and blend film. \u003cstrong\u003ed.\u003c/strong\u003e Resistance of Ag, Au, and Ag/Au electrodes ranging from 0 to 50% uniaxially stretched and released states before and after soaking in artificial sweat during 72 hr. \u003cstrong\u003ee.\u003c/strong\u003e Transfer characteristics of skin-like implantable transistor with different drain voltage. \u003cstrong\u003ef\u003c/strong\u003e. Mobilities and on/off currents of skin-like implantable transistors range from 0 to 50% uniaxially stretched and released states. \u003cstrong\u003eg.\u003c/strong\u003e The skin-like implantable transistor’s mobility and on/off currents under multiple stretching cycles with 50% uniaxial strain. \u003cstrong\u003eh.\u003c/strong\u003e Drain currents changed after soaking in DI water, saline, and PBS for 72 hr. \u003cstrong\u003ei.\u003c/strong\u003e Photograph and structure of a skin-like implantable active-matrix transistor array. \u003cstrong\u003ej.\u003c/strong\u003eMobility mapping of the 5 ⅹ 5 skin-like implantable active-matrix transistor array. \u003cstrong\u003ek.\u003c/strong\u003e Distribution of on current (left) and on/off ratio (right) of 25 devices in the skin-like implantable active-matrix transistor array. \u003cstrong\u003el.\u003c/strong\u003eOn currents (top) and mobilities (bottom) of the skin-like implantable active-matrix transistor array under different uniaxial strains.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-4844804/v1/2fc8ec78a43e0c6fd69ba4ca.png"},{"id":64064678,"identity":"bd59aec0-e933-4980-b67f-05716bc7d16a","added_by":"auto","created_at":"2024-09-06 03:39:46","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":3967739,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eIn vitro\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e biocompatibility tests of various materials composing implantable semiconductors with anti-bacterial test a.\u003c/strong\u003e Schematics of \u003cem\u003ein vitro\u003c/em\u003e tests. \u003cstrong\u003eb.\u003c/strong\u003e Representative fluorescence images of live (green) and dead (red with white arrow) assay (scale bar = 250 μm). \u003cstrong\u003ec.\u003c/strong\u003e Cell viability of each group confirmed with CCK-8 assay (n = 8). \u003cstrong\u003ed.\u003c/strong\u003e Representative wound closure assay images of Ctrl and DPPT-TT: BIIR groups (scale bar = 200 μm) \u003cstrong\u003ee.\u003c/strong\u003e Quantification of the wounded area in each group after the cell migration \u003cstrong\u003ef.\u003c/strong\u003e Proliferation, apoptosis, and migration-related gene expression of hDF in each group. \u003cstrong\u003eg.\u003c/strong\u003e Relative gene expression of macrophage in each group. Antibacterial test of each group using \u003cstrong\u003eh.\u003c/strong\u003e E. Coli and i. S. aureus (*p \u0026lt; 0.05, ***p \u0026lt; 0.001 compared to Ctrl group and \u003csup\u003e$$$\u003c/sup\u003ep \u0026lt; 0.001 compared to PDMS). j. Representative images of green fluorescence from E. coli and S. aureus with various materials (scale bar = 10 μm).\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-4844804/v1/03a48a991e4e8b90b302c673.png"},{"id":64064506,"identity":"fb9044b8-f29c-4480-a925-f70ea466f1f0","added_by":"auto","created_at":"2024-09-06 03:31:46","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":8186020,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eIn vivo\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e biocompatibility test of DPPT-TT:BIIR\u003c/strong\u003e \u003cstrong\u003ea.\u003c/strong\u003e Schematics of \u003cem\u003ein vivo\u003c/em\u003e tests experiment (scale bar = 5 mm). \u003cstrong\u003eb.\u003c/strong\u003eHierarchical clustering heatmap of gene expression in Sham and DB group. \u003cstrong\u003ec.\u003c/strong\u003eDistribution of the measured gene expression levels in Sham and DPPT-TT: BIIR implanted groups. \u003cstrong\u003ed.\u003c/strong\u003e Principal component analysis score based on gene expression measurement in each group. \u003cstrong\u003ee. \u003c/strong\u003eComparison of macrophage phenotype markers between sham and DPPT-TT:BIIR implanted group with western blot analysis. \u003cstrong\u003ef.\u003c/strong\u003eH\u0026amp;E staining of skin retrieved from the implanted site of each group (scale bar = 400 μm). \u003cstrong\u003eg.\u003c/strong\u003e Immunohistochemistry of iNOS (green, left panel), CD163 (green, right panel), and CD68 (red) for pro- and anti-inflammation macrophage staining (scale bar = 100 μm). The lower side of the image is the implanted site.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-4844804/v1/048f1bb7dc55e75488388719.png"},{"id":64064505,"identity":"eed821a8-8fca-4112-9373-d166c391ad4c","added_by":"auto","created_at":"2024-09-06 03:31:46","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1078588,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSkin-like implantable logic circuits for bioelectronics a.\u003c/strong\u003e Schematic of \u003cem\u003ein vivo\u003c/em\u003e subcutaneous implant model for testing function of logic device (scale bar = 5 mm). \u003cstrong\u003eb.\u003c/strong\u003e Photograph of an inverter device. \u003cstrong\u003ec.\u003c/strong\u003e Circuit diagram and logic table of the inverter. \u003cstrong\u003ed.\u003c/strong\u003e VTCs and\u003cstrong\u003e e.\u003c/strong\u003e gains of the inverter at 0% strain (left) and 50% strain (right) before and after implanting to the mouse. \u003cstrong\u003ef.\u003c/strong\u003e Photograph of a NOR device. \u003cstrong\u003eg.\u003c/strong\u003e Circuit diagram and logic table of the NOR device. \u003cstrong\u003eh.\u003c/strong\u003e Photograph of a NAND device. \u003cstrong\u003ei.\u003c/strong\u003eCircuit diagram and logic table of the NAND device. \u003cstrong\u003ej.\u003c/strong\u003e Input and \u003cstrong\u003ek.\u003c/strong\u003eoutput characteristics of the binary logic device at 0% strain and 50% strain before and after implanting to the mouse. \u003cstrong\u003el.\u003c/strong\u003e Comparison of macrophage phenotype markers between the sham and logic device implanted group using western blot analysis. \u003cstrong\u003em.\u003c/strong\u003e Histology of skin site with logic device implantation (scale bar = 200 μm).\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-4844804/v1/797a2824416a7c86c37eef4c.png"},{"id":90476849,"identity":"5c9b0845-1a85-4638-8b9e-9a95ff0d241c","added_by":"auto","created_at":"2025-09-03 07:12:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":23740482,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4844804/v1/cdcb0d9f-672c-460a-93ae-267836b8e20d.pdf"},{"id":64064508,"identity":"824025a2-cf68-4300-bbdb-1a14f95c620a","added_by":"auto","created_at":"2024-09-06 03:31:47","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":20955758,"visible":true,"origin":"","legend":"","description":"","filename":"20240801SupportingInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-4844804/v1/beba24a817522a1ccf05c60d.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Biocompatible Elastomeric Transistors for Implantable Bioelectronics","fulltext":[{"header":"Introduction","content":"\u003cp\u003eImplantable bioelectronic devices are at the forefront of biomedical innovation, enabling continuous \u003cem\u003ein situ\u003c/em\u003e monitoring and modulation of electrophysiological signals.\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Traditional biomedical implants, such as pacemakers, neurostimulators, and insulin pumps, have predominantly relied on rigid inorganic materials like silicon-based semiconductors and metals.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e While these materials have proven effective, their rigidity leads to significant mechanical mismatches with soft biological tissues, resulting in complications such as micro-injury, inflammation, fibrosis, and necrosis over time.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTo address these limitations, recent research has shifted towards developing soft, lightweight, and stretchable bioelectronic devices that seamlessly integrate with human tissues. These devices typically consist of two primary components\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e: biointerface electrodes for signal acquisition and bioelectronic circuits for signal processing. Despite the considerable advancements in hydrogel-based electrodes,\u003csup\u003e\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e creating stretchable transistors for bioelectronic circuits with high biocompatibility and stability in physiological environments remains a long-standing and critical challenge.\u003c/p\u003e \u003cp\u003eStretchable organic electrochemical transistors (sOECTs) were initially proposed for skin-like electronic circuits due to their low Young\u0026rsquo;s modulus and compatibility with biological ionic media.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e However, sOECTs face several drawbacks for electronic circuit applications, including high off-currents and crosstalk due to their ion-based operation, which complicates the provision of individual inputs to an array of transistors.\u003csup\u003e\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Furthermore, the high charging currents at the channel/electrolyte interface of sOECTs pose risks of undesired neural activation \u003cem\u003ein vivo.\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Therefore, there is a pressing need to develop alternative devices to overcome these limitations.\u003c/p\u003e \u003cp\u003eStretchable organic field-effect transistors (sOFETs) are emerging as a promising alternative to sOECTs for high-frequency signal processing.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e These devices leverage well-established field-effect transistor technologies while maintaining mechanical flexibility and preserving electrical performance, making them suitable for integration into bioelectronic circuits.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan additionalcitationids=\"CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e Despite their potential, most sOFETs have been fabricated using industrial-grade elastomers like SEBS, SBS, PU, and PDMS, which are not certified for biocompatibility and can induce chronic foreign body reactions.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Consequently, there is an urgent need for developing biocompatible and stretchable semiconductors for implantable electronics.\u003c/p\u003e \u003cp\u003eMedical elastomers such as bromo butyl rubber (BIIR) have been specifically designed for biomedical applications, meeting stringent biocompatibility standards set by health authorities like ISO 10993 and the European Pharmacopoeia (EP).\u003csup\u003e\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e These elastomers exhibit excellent mechanical properties, including shock absorption, low permeability, aging resistance, and high physical strength, alongside high chemical resistance and low reactivity with microorganisms.\u003csup\u003e\u003cspan additionalcitationids=\"CR36 CR37\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e These properties make BIIR ideal for blending with semiconductors to create stable, biocompatible, and stretchable transistors.\u003c/p\u003e \u003cp\u003eThis study introduces a new approach to fabricating skin-like implantable sOFETs using a cross-linked DPPT-TT and BIIR blend through vulcanization. This work represents the first application of BIIR as an elastomeric matrix for stretchable transistors, addressing the critical need for biocompatibility and mechanical compatibility in bioelectronics. The resulting transistors exhibit stable electrical performance under mechanical strain, maintaining functionality even at 50% elongation. Furthermore, we integrate the dual-layer metallization\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e of Ag and Au to create stretchable and biocompatible electrodes, ensuring robust performance in biofluid environments.\u003c/p\u003e \u003cp\u003eOur comprehensive \u003cem\u003ein vitro\u003c/em\u003e and \u003cem\u003ein vivo\u003c/em\u003e evaluations confirm the biocompatibility and stability of these devices, showing no adverse effects on cell viability, proliferation, or migration and no significant inflammatory response or tissue damage in animal models. This work marks a significant advancement in developing biocompatible and stretchable OFETs and paves the way for their application in a wide range of bioelectronic circuits and implantable devices. The significance of our approach lies in combining a biocompatible elastomeric matrix with advanced semiconductor materials and innovative metallization techniques, providing a robust platform for next-generation implantable bioelectronics. This research addresses critical challenges in the field and opens new avenues for developing medical devices that can seamlessly integrate with human tissues, enhancing diagnostics and therapeutic interventions.\u003c/p\u003e"},{"header":"Results and Discussion","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e1. Material design and vulcanization of implantable semiconductor\u003c/h2\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea presents a schematic of a biocompatible and stretchable semiconductor film comprised of a semiconducting nanofiber network embedded within an elastomer matrix. This innovative design utilizes a molecular blend of a donor-acceptor-based semiconducting polymer with medical-grade rubber. Specifically, we used poly[(dithiophene)-alt-(2,5-bis(2-octyldodecyl)-3,6-bis(thienyl)-diketopyrrolopyrrole)] (DPPT-TT) as the polymer semiconductor and bromo isobutylene isoprene rubber (BIIR) as the biocompatible elastomer matrix. The blend film was chemically cross-linked through vulcanization, a well-established method to enhance the mechanical property of medical rubbers using additives such as sulfur (crosslinker), dipentamethylenethiuram tetrasulfide (DPTT, accelerator), and stearic acid (initiator) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). The phase separation forming the semiconducting nanofiber network results from the surface energy disparity between DPPT-TT and BIIR, enabling the formation of a highly interconnected DPPT-TT nanofiber network within the elastic BIIR matrix, thus imparting stretchability (Supplementary Fig.\u0026nbsp;2).\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTo determine the optimal blend ratio for electrical and mechanical properties, we evaluated the vulcanized semiconductor films across various weight ratios of DPPT-TT (1:9 to 9:1). The results showed stable field-effect mobility across ratios from 9:1 to 3:7, indicating that the semiconducting percolation path is preserved up to a 0.7 weight fraction of BIIR (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec, Supplementary Fig.\u0026nbsp;3). This ratio produced a highly elastic semiconducting film that sustained up to 100% strain without mechanical damage, as confirmed by optical microscopy (OM) images of the 3:7 blend film (Supplementary Fig.\u0026nbsp;4). Conversely, films with lower BIIR content (9:1 to 5:5) exhibited cracks at 25% strain, emphasizing the necessity of higher BIIR content for intrinsic stretchability (Supplementary Fig.\u0026nbsp;4). Therefore, the 3:7 DPPT-TT blend ratio was optimized for the field-effect mobility, crack-onset strain, and integrity of the semiconducting nanofiber network (Supplementary Figs.\u0026nbsp;5 and 6).\u003c/p\u003e \u003cp\u003eTo verify the vulcanization of BIIR in the blend film, we performed FT-IR analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed, Supplementary Fig.\u0026nbsp;7). The vulcanization process involves three key stages: initiation for radical formation, propagation for crosslinking BIIR with sulfur and termination for end of the reaction. The reduction in the C-Br (667 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e) peaks in the FT-IR spectra post-vulcanization confirmed the successful initiation (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed). The significant reduction in the C\u0026thinsp;=\u0026thinsp;C peak (1538 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e) in neat BIIR post-vulcanization indicates successful propagation (Supplementary Fig.\u0026nbsp;7).\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e The blend film has difficulty decoupling the C\u0026thinsp;=\u0026thinsp;C peak of BIIR because DPPT-TT has a similar C\u0026thinsp;=\u0026thinsp;C peak, while the C\u0026thinsp;=\u0026thinsp;C peak was reduced in the neat BIIR film. The unchanged C\u0026thinsp;=\u0026thinsp;C peak of the blend film after the vulcanization indicates that the conjugated bond structure of DPPT-TT was preserved. The increased modulus observed in Derjaguin-Muller-Toporov (DMT) modulus mapping further confirmed vulcanization, enhancing the elasticity of the blend film while preserving its pristine nanomorphology (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ee). Additionally, the unchanged UV-vis absorption spectra before and after vulcanization indicate that the vulcanization process selectively crosslinks BIIR chains without disrupting the conjugated molecular structure of DPPT-TT (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ef, Supplementary Figs.\u0026nbsp;8 and 9). Transistors fabricated with vulcanized blend films exhibited higher mobility and on/off ratio, suggesting that vulcanization also serves as a thermal annealing process, optimizing the morphology of the semiconducting polymer film while crosslinking the BIIR elastomer (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ei). We also performed X-ray photoelectron spectroscopy (XPS) depth profiling of the vulcanized blend film, which revealed a uniform distribution of S atoms from DPPT-TT nanofibers throughout the semiconductor film, facilitating effective charge injection and transport in both vertical and horizontal directions (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eg). The dichroic ratio of the vulcanized blend film as a function of applied strain (0%-50%) showed a linear increase, indicating the alignment of semiconducting nanofibers along the strain direction without mechanical cracking (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eh, Supplementary Fig.\u0026nbsp;10). Furthermore, atomic force microscopy (AFM) and conductive AFM (C-AFM) images showed a highly interconnected DPPT-TT nanofiber network aligned with the strain direction, providing a strain-insensitive conductive path (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ej, k). This morphology was reflected in the stable electrical performance of the FETs, with negligible changes in mobility under strains from 0\u0026ndash;100% on a rigid substrate (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003el, Supplementary Figs.\u0026nbsp;11 and 12). Additionally, the mobility of the blend film remained consistent after 1000 stretching cycles at 100% strain, demonstrating excellent mechanical durability (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003em, Supplementary Fig.\u0026nbsp;13). These results confirm that the vulcanized blend film is highly stretchable, with the nanostructure of DPPT-TT well-preserved under mechanical deformation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2. Skin-like implantable active-matrix transistor\u003c/h2\u003e \u003cp\u003eTo develop skin-like and biocompatible implantable transistors, we employed a dual-layer metallization technique using silver (Ag) and gold (Au) to create highly conductive, stretchable, and biocompatible electrodes.\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e Ag was selected for its excellent electrical contact properties, while Au provided robust protection against biofluid-induced corrosion, thereby enhancing the durability of the electrodes \u003cem\u003ein vivo\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea, Supplementary Fig.\u0026nbsp;14). X-ray photoelectron spectroscopy (XPS) depth profiling confirmed an intermixing region of carbon and silver atoms, which enhances both stretchability and adhesion (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). Initial resistance measurements demonstrated that the Ag-Au electrodes maintained low resistance after soaking in artificial sweat for 72 hr, indicating their superior corrosion resistance (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). Transistors fabricated with Ag-Au dual-layer electrodes exhibited electrical performance comparable to those with pure Ag electrodes, with the added benefit of enhanced durability in biofluid environments (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec). The Ag-Au electrodes were stretchable up to 50% while maintaining a resistance of 10\u003csup\u003e2\u003c/sup\u003e Ω even after soaking in artificial sweat for 72 hr (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed, Supplementary Fig.\u0026nbsp;15)providing the viability for highly conductive, stretchable, and biocompatible electrodes in skin-like implantable transistors.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee shows the typical transfer characteristics of a skin-like implantable transistor at various drain voltages, demonstrating its capability to operate under low voltage conditions essential for safe \u003cem\u003ein vivo\u003c/em\u003e applications (Supplementary Fig.\u0026nbsp;18). The transistors maintained stable electrical performance and mechanical durability, retaining their initial field-effect mobility and on/off ratios up to 50% strain, even after 10,000 stretching cycles (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ef, g, Supplementary Fig.\u0026nbsp;19\u0026ndash;22). This robustness was further validated by negligible changes in drain current after 72 hr of soaking in various artificial sweat solutions (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eh, Supplementary Fig.\u0026nbsp;23), highlighting the effectiveness of Ag-Au dual-layer metallization in creating resilient and reliable electrodes for stretchable transistors.\u003c/p\u003e \u003cp\u003eTo further validate the practical applicability of our devices in circuits, we fabricated a 5\u0026times;5 active-matrix array of skin-like implantable transistors. The array demonstrated uniform field-effect mobility and drain current across all devices, confirming its high yield and suitability for bioelectronic applications (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ej, k). The field-effect mobility of the active-matrix array showed consistent performance, with minimal variation in on-current and mobility under different uniaxial strains (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003el, Supplementary Fig.\u0026nbsp;24).\u003c/p\u003e \u003cp\u003e \u003cb\u003e3.\u003c/b\u003e \u003cb\u003eIn vitro\u003c/b\u003e \u003cb\u003ebiocompatibility tests for skin-like implantable transistors\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cem\u003eIn vitro\u003c/em\u003e biocompatibility tests were conducted using human dermal fibroblasts (hDFs) and macrophages (Mφ) to evaluate the safety and effectiveness of the materials used in the implantable semiconductor and transistor. The tests assessed the impact of each material\u0026mdash;BIIR, SEBS, blend film, and fully assembled transistor\u0026mdash;on cell viability, migration, and gene expression.\u003c/p\u003e \u003cp\u003eA schematic overview of the \u003cem\u003ein vitro\u003c/em\u003e experiment is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea. Live/dead assays and CCK-8 assays were used to assess the cell viability. Fluorescence microscopy results from the live/dead assay showed green signals for live cells and red signals (with white arrows) for dead cells, with minimal red signals observed across all material groups, confirming high cell viability (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb). CCK-8 assay results further supported these findings, showing no significant differences in cell viability among the groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec). These results indicate that all materials used in the implantable semiconductor and transistor have prominent biocompatibility.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe effect of each material on cell migration was investigated using an \u003cem\u003ein vitro\u003c/em\u003e wound closure assay with hDFs. Similar wound closure rates across all groups indicated that the materials did not impair the migration properties of hDFs (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed, e, Supplementary Fig.\u0026nbsp;25). Gene expression analysis using qRT-PCR revealed no significant differences in the expression of proliferation-related genes (PCNA and Ki67) and apoptosis-related genes (BAX and BCL-2) among the groups, except for a substantial increase in CXCR4 expression in the blend film group. This increase suggests the enhanced migration property of hDFs in the presence of the blend film (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ef).\u003c/p\u003e \u003cp\u003eInflammatory potential was assessed by profiling gene expression in macrophages (Mφ, Raw264.7 cells). After co-culturing Mφ with each material, the expression of specific markers for pro-inflammatory (M1) macrophages was measured. BIIR induced the lowest level of CD86 expression. At the same time, other groups showed similar levels (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eg). The blend film and BIIR groups exhibited balanced profiles in CD80, STAT1, and iNOS expression compared to the control. In contrast, the SEBS group showed the highest gene expression level, indicating a higher propensity for inducing inflammation.\u003c/p\u003e \u003cp\u003eThe antibacterial properties of the materials were evaluated using genetically modified strains of Escherichia Coli (E. Coli) and Staphylococcus Aureus (S. Aureus) expressing green fluorescent protein (GFP). The positive control group (gelatin-coated glass coverslip) showed significantly higher bacterial growth, while the BIIR, SEBS, blend film, and transistor groups exhibited no significant differences in bacterial numbers, indicating effective anti-bacterial properties (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eh, i). Representative fluorescence images confirmed lower bacterial viability on the blend film than bare PDMS (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ej). These results indicate an enhanced anti-bacterial effect of the fabricated DPPT-TT: BIIR, suggesting their potential application in medical devices. \u003cem\u003eIn vitro\u003c/em\u003e tests demonstrated that the DPPT-TT blend and the fully assembled transistors are highly biocompatible, supporting cell viability, proliferation, and migration without inducing significant inflammatory responses.\u003c/p\u003e \u003cp\u003e \u003cb\u003e4.\u003c/b\u003e \u003cb\u003eIn vivo\u003c/b\u003e \u003cb\u003ebiocompatibility tests for skin-like implantable transistor\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTo evaluate the \u003cem\u003ein vivo\u003c/em\u003e biocompatibility of our blend film, a comprehensive set of tests was conducted using a subcutaneous implant model in BALB/C mouse (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea). These tests aimed to assess the inflammatory response, tissue integration, and overall compatibility of the materials over a prolonged period. Hierarchical clustering heatmap analysis revealed no significant differences between the sham and implanted groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb). Principal component analysis (PCA) was performed on genetic data involving 19 genes per group. Five principal components were identified, with PC1 accounting for 46.54% (eigenvalue: 8.843) and PC2 for 35.06% (eigenvalue: 6.660) of the variance. IL-10 and iNOS (positive direction) and IL-6 (negative direction) significantly influenced PC1, while IL-1β (positive direction) and K-14 (negative direction) markedly influenced PC2 (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ec). The distribution of PC scores for sham and implanted groups showed no significant differences, demonstrating the materials\u0026rsquo; compatibility with biological tissues and potential for long-term implantation (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ed).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMacrophage phenotyping confirmed the absence of significant inflammatory responses. Western blot analysis of macrophage markers showed similar levels of M1 and M2 macrophage marker expression in both sham and implanted groups, indicating that no severe inflammation was observed, which is essential for maintaining tissue homeostasis (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ee and Supplementary Fig.\u0026nbsp;26). Histological analysis using hematoxylin and eosin (H\u0026amp;E) staining provided additional evidence of biocompatibility. Tissue sections around the implants displayed normal collagen layer formation and no significant differences in tissue architecture compared to control groups 30 days after the implantation (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ef). This suggests that the materials integrate well with the host tissue without causing adverse reactions. Immunohistochemistry for M1 and M2 macrophage markers further supported these findings. Sections stained for iNOS (M1 marker), CD163 (M2 marker), and CD68 (Mφ marker) showed no significant differences between the sham and implanted groups, confirming that the blend film implantation did not provoke an inflammatory response (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eg).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e5. Skin-like implantable circuits for bioelectronics\u003c/h3\u003e\n\u003cp\u003eTo demonstrate the practical application of our skin-like implantable transistors in bioelectronic devices, we developed and tested various logic circuits, including inverters, NOR, and NAND gates, \u003cem\u003ein vivo\u003c/em\u003e (Supplementary Fig.\u0026nbsp;27). These circuits are essential components for complex bioelectronic systems, enabling advanced signal processing capabilities within the human body.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea provides a schematic overview of the subcutaneous implantation of logic circuits fabricated with skin-like implantable transistors. These circuits were designed to maintain stable electrical performance under mechanical strain and physiological conditions. Pseudo-CMOS design-based inverter, NOR, and NAND circuits (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eb, f, and h) were fabricated for the versatility of our approach. To validate the functionality of our logic circuits \u003cem\u003ein vivo\u003c/em\u003e, we implanted the devices into BALB/C mice and monitored their performance over 3 days. The inverter circuits, fundamental building blocks for digital logic, showed stable voltage transfer characteristics (VTCs) with apparent switching behavior under 50% strain (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ed). The gain of the inverters remained consistent, even after implantation and stretching, underscoring their mechanical robustness and stability in a biological environment (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ee). This performance is crucial for accurate signal processing in bioelectronic applications. The NOR and NAND gates maintained their logical output states under the same conditions, demonstrating robust performance despite mechanical deformation (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ej, k and (Supplementary Fig.\u0026nbsp;28\u0026ndash;31). The ability of these logic gates to function correctly under strain is vital for developing reliable and flexible bioelectronic circuits.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe NAND and NOR gate retained stable electrical characteristics, including consistent output voltages, throughout the implantation period (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eh). This long-term stability in a physiological environment highlights the suitability of our devices for real-world bioelectronic applications. \u003cem\u003eIn vivo\u003c/em\u003e biocompatibility was assessed by analyzing inflammation markers and histology. Figure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003el and Supplementary Fig.\u0026nbsp;32 present quantitative data and representative images of western blot bands for M1 and M2 macrophage markers and inflammation-related markers. All markers, except CD163, showed similar results to the sham group, indicating no significant inflammation with the logic device implantation, comparable to the sham group. Short-term (3 days) implantation showed no immune cell infiltration at the implanted site in either group (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003em). This suggests that our semiconductor-based circuits are suitable for implantable electronics and can function effectively within a biological environment.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe have developed biocompatible elastomeric organic field-effect transistors (OFETs) using a vulcanized blend film of semiconducting polymer nanofiber and medical-grade elastomer. These transistors exhibit remarkable mechanical flexibility and maintain stable electrical performance under significant strain, up to 100%. Integrating Ag-Au dual-layer metallization for the electrodes ensures excellent electrical contact and resistance to biofluid-induced corrosion. Our comprehensive \u003cem\u003ein vitro\u003c/em\u003e biocompatibility assessments with human dermal fibroblasts and macrophages confirmed that the DPPT-TT blend does not negatively impact cell viability, proliferation, and migration or cause inflammation and exhibits superior anti-bacterial properties. An \u003cem\u003ein vivo\u003c/em\u003e study using a subcutaneous implant model in BALB/C mice demonstrated no significant inflammatory response or tissue damage, confirming the materials\u0026rsquo; suitability for long-term implantation. Furthermore, the fabricated skin-like implantable transistors and logic circuits, including active-matrix arrays, inverters, NOR, and NAND gates, maintained their functionality under mechanical stress and physiological conditions. These findings underscore the potential of these biocompatible and stretchable OFETs for a wide range of bioelectronic applications, offering a promising platform for advanced medical devices aimed at seamless integration with biological tissues. This work represents a significant advancement in developing implantable bioelectronics, addressing critical challenges of mechanical mismatch and biocompatibility. Future research will focus on optimizing device performance and exploring broader applications in medical diagnostics and therapeutic interventions, paving the way for the next generation of bio-integrated electronics.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSunwoo, Sung-Hyuk, et al. Wearable and implantable soft bioelectronics: device designs and material strategies. Annual review of chemical and biomolecular engineering 12.1,359\u0026ndash;391 (2021).\u003c/li\u003e\n\u003cli\u003eSong, Yu, Jihong Min, and Wei Gao. Wearable and implantable electronics: moving toward precision therapy. ACS nano 13.11,12280\u0026ndash;12286 (2019).\u003c/li\u003e\n\u003cli\u003eHan, Won Bae, et al. Materials, devices, and applications for wearable and implantable electronics. ACS Applied Electronic Materials 3.2,485\u0026ndash;503 (2021).\u003c/li\u003e\n\u003cli\u003eMond, Harry G., and Alessandro Proclemer. 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Tissue Eng Regen Med 21, 421\u0026ndash;435 (2024).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eMaterials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAu (99.99%, 3 mm granules) was purchased from SYSCIENCE\u0026nbsp;(Seoul, Republic of Korea). Ag (99.99%, 3\u0026ndash;5mm granule) was purchased from SYSCIENCE. Poly[(dithiophene)-alternate-(2,5-bis(2-octyldodecyl)-3,6-bis(thienyl)-diketopyrrolopyrrole)] (DPPT-TT) was purchased from Derthon (Shenzhen, China). Bromo butyl rubber (BIIR) was provided by Samsung Medical Rubber. SEBS H 1062 and SEBS H 1052 were provided by Asahi KASEI. H1062 (S/EB weight ratio, 18/82) and H1052 (S/EB weight ratio, 20/80) were used as the elastic substrate and dielectric layer, respectively. Anhydrous toluene (99.8%), anhydrous chlorobenzene (99.8%), anhydrous chloroform (99.8%), sulfur, dipentamethylenethiuram tetrasulfide, trichloro(octadecyl)silane (OTS), and stearic acid were purchased from Sigma\u0026ndash;Aldrich (St. Louis, Missouri, MO, USA). Poly(dimethylsiloxane) (PDMS, Sylgard 184) and\u0026nbsp;the curing agent were purchased from Dow Corning\u0026nbsp;(Midland, MI, USA). The PDMS was cured at a ratio of 11:1 (base/curing agent, w/w) at 55\u0026nbsp;℃ overnight for the stamp. Silicon wafer (SiO\u003csub\u003e2\u003c/sub\u003e/Si, \u0026lt;100\u0026gt;, 1\u0026ndash;30 Ω, 300\u0026nbsp;nm SiO\u003csub\u003e2\u003c/sub\u003e) was purchased from iTASCO. All\u0026nbsp;the chemicals were used as received without further purification.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDevice fabrication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOrganic thin film transistor on rigid substrate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe solution for the semiconductor was prepared by dissolving 0.8 wt% of DPPT-TT, BIIR, and cross-linker at various blending ratios in anhydrous chlorobenzene at 120 \u0026deg;C for 4 h. BIIR, sulfur, DPTT, and stearic acid were added in a ratio of 100:1:1:5 and used as\u0026nbsp;the elastic matrix of the semiconducting films.\u0026nbsp;The solutions for the semiconductor were spun on an OTS-treated SiO\u003csub\u003e2\u003c/sub\u003e/Si wafer at 800 rpm for 1 min after filtration with a PTFE-D (0.2 \u0026mu;m) filter. The semiconducting film\u0026nbsp;was annealed at 150 \u0026deg;C for 1 h. All processes\u0026nbsp;were performed under a N\u003csub\u003e2\u003c/sub\u003e atmosphere in\u0026nbsp;a glove box (H\u003csub\u003e2\u003c/sub\u003eO \u0026lt; 0.01 parts per million (ppm) and O\u003csub\u003e2\u003c/sub\u003e \u0026lt; 0.01 ppm). The dielectric solution was prepared by dissolving 60 mg/mL of SEBS H1052 in toluene at 60 \u0026deg;C for 4 h. The dielectric solution was spun at 1000 rpm for 1 min on an indium tin oxide (ITO; sheet resistance, 20 ohm/square) glass substrate. The semiconducting film was transferred from\u0026nbsp;an OTS-treated wafer onto\u0026nbsp;an SEBS/ITO glass substrate\u0026nbsp;using PDMS stamps. The Ag source/drain electrodes were evaporated at 0.2 nm/s using a thermal evaporator. The channel length and width were 1000 and 150 \u0026mu;m, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFully stretchable transistors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe elastic substrates for\u0026nbsp;the fully stretchable transistor were prepared by casting SEBS H1062 (100 mg/ml in toluene) onto\u0026nbsp;glass slides. After drying overnight, the Au (30\u0026nbsp;nm)/Ag gate electrode (30 nm) was evaporated onto an SEBS substrate at 0.2 nm/s under high vacuum (below 5.0\u0026nbsp;\u0026times; 10-6 torr). The SEBS H1052 dielectric and semiconducting film (3:7 ratio of DPPT-TT to BIIR) were continuously transferred onto\u0026nbsp;the gate electrode.\u0026nbsp;Au/Ag source/drain electrodes (30 nm each) were evaporated onto semiconducting films at a speed of 0.05 nm/s. The channel length and width were 1000 and 150 \u0026mu;m, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFor active-matrix transistor array\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures for the fabrication of the active-matrix transistor array were identical to those for the fabrication of fully stretchable transistors, except for the dielectric film, which was designed using a different concentration (75 mg/ml in toluene, spin-coated at 1000 rpm for 1 min) to obtain a thicker dielectric film (1.9 \u0026mu;m). The channel length and width were 2000 and 150 \u0026mu;m, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFor logic gate devices including inverter, NAND, and NOR\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe SEBS substrate, semiconducting thin film, and dielectric layer were prepared using the same process as\u0026nbsp;that for the fully stretchable active-matrix transistor array. The bottom Au\u0026nbsp;(30 nm)/Ag electrodes (30 nm) were evaporated onto\u0026nbsp;the SEBS H1062 substrates designed for each logic gate. The semiconducting films and dielectric layers were sequentially transferred onto\u0026nbsp;the Ag electrode. Finally, the top Au (30 nm)/Ag electrodes (30 nm) were thermally evaporated using\u0026nbsp;a designed pattern.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStretchable and biocompatible encapsulation layer\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe encapsulation films were prepared by casting the BIIR solution (120 mg/ml in chlorobenzene) on a TeflonTM mold, which was dried for 2 d and annealed at 150 \u0026deg;C for 30 min. The encapsulation films were applied to both sides (top\u0026nbsp;and bottom) of\u0026nbsp;the\u0026nbsp;stretchable device.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCharacterization\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The devices were stabilized by aging them overnight in an autodry desiccator (24% humidity, 27 ˚C). The electrical characteristics of\u0026nbsp;the devices were measured using a probe station connected\u0026nbsp;to\u0026nbsp;a KEITHLEY 4200 under atmospheric conditions, and a vacuum probe station with a Peltier device was\u0026nbsp;connected to a KEITHLEY 2636B to control the temperature. The\u0026nbsp;dielectric capacitance\u0026nbsp;was measured using\u0026nbsp;a probe station connected to an LCR meter (Keysight 4274A).\u0026nbsp;UV-Vis-NIR spectroscopy was performed using a Jasco V-770. The surface structure was observed using atomic force microscopy (AFM; Bruker MultiMode 8-HR) under ambient conditions. Optical microscopy (OM) images were\u0026nbsp;acquired using a Leica 2DM4 M. The\u0026nbsp;film thickness\u0026nbsp;was measured using an ellipsometer (WONWOO STRC-2000). To obtain stretched OM and AFM images,\u0026nbsp;the semiconductor was\u0026nbsp;transferred using the PDMS stamp method.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCell culture\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ehDFs were purchased from Lonza (Basel, Switzerland).\u0026nbsp;The\u0026nbsp;hDFs were cultured in Dulbecco\u0026apos;s modified Eagle\u0026apos;s medium (DMEM; Gibco BRL, Gaithersburg, Maryland, USA) supplemented with 10% (v/v) fetal bovine serum (FBS; Gibco BRL) and 1% (v/v) penicillin/streptomycin (PS; Gibco BRL). The cells were incubated at 37\u0026nbsp;\u0026deg;C with 5% CO\u003csub\u003e2\u003c/sub\u003e saturation. The cell culture medium was changed every 2 d. Cells within eight passages were used for the experiments. Raw 264.7 cells were cultured in DMEM (Gibco BRL) supplemented with 10% (v/v) FBS and 1% (v/v) PS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFDA/EB staining assay\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFluorescein diacetate (FDA, Sigma\u0026ndash;Aldrich) and ethidium bromide (EB, Sigma\u0026ndash;Aldrich)\u0026nbsp;were used for fluorescein diacetate/ethidium bromide staining.\u0026nbsp;FDA\u0026nbsp;(green) stains the cytoplasm of viable cells, whereas\u0026nbsp;EB\u0026nbsp;(red) stains the nuclei of non-viable cells. The staining solution was freshly prepared by combining 10 mL of FDA stock solution (1.5 mg/mL\u0026nbsp;FDA in dimethyl sulfoxide), 5\u0026nbsp;mL of EB stock solution (1\u0026nbsp;mg/mL EB in phosphate-buffered saline, PBS), and 3\u0026nbsp;mL of PBS. hDFs were then incubated in the staining solution for 3\u0026nbsp;min at 37\u0026nbsp;\u0026deg;C. After staining, the samples were washed twice with PBS and examined under a\u0026nbsp;fluorescence microscope\u0026nbsp;(DFC 3000\u0026nbsp;G; Leica, Wetzlar, Germany).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCell viability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCell proliferation was analyzed using the Cell Counting Kit-8 (CCK-8; Sigma\u0026ndash;Aldrich) assay. The hDFs were seeded in 24-well plates (2 \u0026times; 10\u003csup\u003e4\u003c/sup\u003e cells/well), and CCK-8 was used to measure cell proliferation for 1 d after co-culturing with each material using Transwell. The cells were washed in PBS, and\u0026nbsp;the medium was replaced with a culture medium containing a CCK-8 solution (10%,\u0026nbsp;v/v). After 2 h of incubation at 37 \u0026deg;C, the absorbance of each well was measured at 450\u0026thinsp;nm (Infinite F50; TECAN, M\u0026auml;nnedorf, Switzerland).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIn vitro wound closure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe hDFs were grown in confluence in 6-well plates\u003csup\u003e42\u003c/sup\u003e and then replenished with DMEM (Gibco BRL). Thereafter, the cells were co-cultured sequentially using BIIR, SEBS, DPPT:TT:BIIR, and logic devices for 1 d. A straight scratch was made on the\u0026nbsp;hDF layer\u0026nbsp;using a P1000 pipette tip. After incubation for 24 h, the gap width of the scratch following repopulation was measured and compared with the initial gap size at 0 h. The size of the denuded area was determined at each time point from\u0026nbsp;the digital images using Adobe Photoshop CC (Adobe Systems, CA, USA).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReal-time polymerase chain reaction (qRT-PCR)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe relative gene expression levels of human \u003cem\u003eBCL-2, BAX, CXCR-4, PCNA, Ki67,\u0026nbsp;\u003c/em\u003eand mouse\u003cem\u003e\u0026nbsp;CD80, CD86, iNOS1, iNOS2,\u0026nbsp;\u003c/em\u003eand\u003cem\u003e\u0026nbsp;STAT1\u0026nbsp;\u003c/em\u003ewere quantified by performing qRT-PCR\u003cem\u003e.\u003c/em\u003e Human-specific gene primers were utilized for \u003cem\u003ein vitro\u003c/em\u003e \u003ca href=\"https://www.sciencedirect.com/topics/engineering/dermal-fibroblast\" title=\"Learn more about hDF from ScienceDirect's AI-generated Topic Pages\"\u003ehDF\u003c/a\u003e analysis. Mouse gene primers were used for \u003cem\u003ein vivo\u003c/em\u003e skin tissue analysis. The total ribonucleic acid (RNA) was extracted from the samples using 1 mL of Trizol reagent (Life Technologies, Inc., Carlsbad, CA, USA) and 200 \u0026mu;L of chloroform. The lysed samples were centrifuged at 12,000 rpm for 10 min at 4 \u0026deg;C. The RNA pellet was\u0026nbsp;then washed with 75% (v/v) ethanol in water and dried. Subsequently,\u0026nbsp;the samples were dissolved in RNase-free water. For qRT-PCR, the SsoAdvanced\u0026trade; Universal SYBR Green Supermix kit (Bio-Rad, Hercules, CA, USA) and CFX Connect\u0026trade; real-time PCR detection system (Bio-Rad) were used.\u0026nbsp;Table 1\u0026nbsp;lists the primers used for qRT-PCR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Sequences of the qRT-PCR primer.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.622296173044926%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimers\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"73.37770382695507%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSequences\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.622296173044926%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eHuman\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eGAPDH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"73.37770382695507%\" valign=\"top\"\u003e\n \u003cp\u003eF : 5\u0026prime;-GTCGGAGTCAACGGATTTGG-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003eR : 5\u0026prime;-GGGTGGAATCATTGGAACAT-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.622296173044926%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eHuman\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eBCL-2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"73.37770382695507%\" valign=\"top\"\u003e\n \u003cp\u003eF : 5\u0026prime;-CAACATCGCCCTGTGGATGA-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003eR : 5\u0026prime;-GGGCCAAACTGAGCAGAGTC-3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.622296173044926%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eHuman\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eBAX\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"73.37770382695507%\" valign=\"top\"\u003e\n \u003cp\u003eF : 5\u0026prime;-GCAACTTCAACTGGGGCCGGG-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003eR : 5\u0026prime;-GATCCAGCCCAACAGCCGCTC-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.622296173044926%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eHuman\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eCXCR-4\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"73.37770382695507%\" valign=\"top\"\u003e\n \u003cp\u003eF : 5\u0026prime;-TAC ACC GAG GAA ATG GGC TCA-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003eR : 5\u0026prime;-AGA TGA TGG AGT AGA TGG TGG G-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.622296173044926%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eHuman\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cem\u003ePCNA\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"73.37770382695507%\" valign=\"top\"\u003e\n \u003cp\u003eF : 5\u0026prime;-AGG GCT GAA GAT AAT GCT GAT ACC-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003eR : 5\u0026prime;-CTC CTG TTC TGG GAT TCC AAG TTG-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.622296173044926%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eHuman\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eKi67\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"73.37770382695507%\" valign=\"top\"\u003e\n \u003cp\u003eF : 5\u0026prime;-TGACCCTGATGAGAAAGCTCAA-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003eR : 5\u0026prime;-CCCTGAGCAACACTGTCTTTT-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.622296173044926%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eMouse\u003cbr\u003e\u003cem\u003eCD80\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"73.37770382695507%\" valign=\"top\"\u003e\n \u003cp\u003eF : 5\u0026prime;-AGTTTCTCTTTTTCAGGTTGTGAA-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003eR : 5\u0026prime;-ACATGATGGGGAAAGCCAGG-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.622296173044926%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eMouse\u003cbr\u003e\u003cem\u003eCD86\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"73.37770382695507%\" valign=\"top\"\u003e\n \u003cp\u003eF : 5\u0026prime;-CTTACGGAAGCACCCACGAT-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003eR : 5\u0026prime;-CGGCAGATATGCAGTCCCAT-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.622296173044926%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eMouse\u003cbr\u003e\u003cem\u003eiNOS\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"73.37770382695507%\" valign=\"top\"\u003e\n \u003cp\u003eF : 5\u0026prime;- CTGGGAGCGCTCTAGTGAAG-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003eR : 5\u0026prime;- CTCTCCACTGCCCCAGTTTT-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.622296173044926%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eMouse\u003cbr\u003e\u003cem\u003eSTAT1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"73.37770382695507%\" valign=\"top\"\u003e\n \u003cp\u003eF : 5\u0026prime;-GATCGCTTGCCCAACTCTTG-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003eR : 5\u0026prime;-ACTGTGACATCCTTGGGCTG-3\u0026prime;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAnti-bacterial test\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe antibacterial test was conducted using two representative bacterial strains commonly associated with infections on medical devices: \u003cem\u003eEscherichia coli\u003c/em\u003e (E. coli) and \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (S. aureus). In this study, we used the genetically modified E. coli C2925 and S. aureus NCTC 8325-4 strains to express the green fluorescent protein (GFP). Both bacterial stains were cultured in a tryptic soy broth medium with ampicillin (100 \u0026mu;g/ml) and chloramphenicol (10 \u0026mu;g/ml) at 37 ℃ for 24 h, until an OD600 of 108 CFUs/mL was reached in fresh media. Each strain was applied to a film sample (n = 6) prepared in a 24-well plate at a concentration of 5 \u0026times; 10\u003csup\u003e7\u0026nbsp;\u003c/sup\u003eCFU/ml per well. Gelatin (0.1% w/w)-coated glass coverslips promoting bacterial adhesion and growth served as positive controls along with bare PDMS blocks. After incubating at 37 ℃ for 24 h, non-adhered bacteria were removed by washing three times with PBS, and the bacterial colonies were fixed with a 4% paraformaldehyde (PFA) solution for 10 min, followed by two washes with PBS. The bacteria were imaged using\u0026nbsp;confocal microscopy (LSM800, Carl Zeiss AG, Germany) at 40X magnification at the BT Research Facility Center, Chung-Ang University. The z-stack images were processed using the maximum projection method, and the fluorescence intensity was measured using ImageJ (NIH, Bethesda, MD, USA) to quantify the relative number of bacteria adhered to each sample.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eIn vivo\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;subcutaneous DPPT-TT:BIIR and logic device implantation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSix-week-old female Balb/C mice (20\u0026ndash;25\u0026thinsp;g body weight; Orient, Seoul, Republic of Korea) were anesthetized using 200\u0026thinsp;\u0026mu;L of xylazine (20\u0026thinsp;mg/kg) and ketamine (100\u0026thinsp;mg/kg) diluted in normal saline solution. Hair\u0026nbsp;was removed from the right side of the back\u0026nbsp;using a combination of animal electric clippers and\u0026nbsp;nair (less than 1\u0026thinsp;min). The implanted site was marked with\u0026nbsp;a 10\u0026nbsp;\u0026times; 10 mm\u003csup\u003e2\u003c/sup\u003e stamp on the lateral flank of each mouse. The epidermis, dermis, and stratum corneum were surgically excised at the top and right sides.\u0026nbsp;The skin was opened by flipping. For\u0026nbsp;the DPPT-TT:BIIR (D:B) and logic device groups, each material\u0026nbsp;was carefully implanted into the open area. An\u0026nbsp;identical surgical procedure was performed for the sham group without implantation. After 3 and 30 d, the subcutaneously implanted mice were sacrificed for \u003cem\u003ein vivo\u003c/em\u003e analysis. All\u0026nbsp;the animals were cared for in accordance with the Guidelines for the Care and Use of Laboratory Animals of Sungkyunkwan University (SKKUIACUC2022-04-40-1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWestern blotting\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe retrieved tissues were sectioned and lysed in RIPA buffer (Rockland Immunochemicals,\u0026nbsp;Inc., Limerick, PA, USA). After centrifugation at 10,000 g for 10 min, the supernatant was prepared as a protein extract. Protein concentrations were determined using a BCA assay (Pierce Biotechnology, Rockford, IL, USA). Equal amounts of protein from each sample were mixed with the sample buffer and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) using a 10% (v/v) resolving gel. The separated proteins were transferred to immune-blot PVDF membranes (Bio-Rad). The membranes were blocked with 5% (w/v) skim milk in Tris-buffered saline (TBS-T; 50 mM Tris\u0026ndash;HCl (pH 7.5), 150 mM NaCl, 2.5 mM KCl) and incubated for 1 h at 25 \u0026deg;C. Then, the membranes were probed overnight at 4 \u0026deg;C with antibodies against glyceraldehyde 3-phosphate dehydrogenase (GAPDH) (Abcam, ab9485, Cambridge, UK), CD163 (Abcam, ab182422), CD206 (Abcam, ab64693), STAT1 (Cell Signaling Technology, CS9172), STAT6 (Cell Signaling Technology, CS9362), and TGF-\u0026beta; (Cell Signaling Technology, CS3711). Thereafter, the membranes were incubated in horseradish peroxidase-conjugated secondary antibodies (R\u0026amp;D Systems, HAF008 for GAPDH, HAF017 for CD163, CD206, STAT1, STAT6, and TGF-\u0026beta;, Minneapolis, MN, USA) for 1 h at 25 \u0026deg;C, followed by the addition of an ECL reagent (TransLab, Daejeon, Republic of Korea). The blots were developed in a dark room, and luminescence was recorded using an X-ray blue film (Agfa HealthCare NV, Mortsel, Belgium).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHistology\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eImpaired skin tissue specimens retrieved 3 d post-treatment were fixed with a 4% PFA solution and embedded at an optimum cutting temperature (OCT) compound (SciGen Scientific, Gardenas, USA). Thereafter, 10\u0026nbsp;\u0026mu;m sections obtained from the specimens were stained with hematoxylin and\u0026nbsp;eosin\u0026nbsp;(H\u0026amp;E) to assess re-epithelialization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImmunohistochemistry\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor immunohistochemical staining, the samples embedded in OCT compound were cut into 10\u0026nbsp;\u0026mu;m-thick sections at \u0026minus;22\u0026nbsp;\u0026deg;C. To stain the pro-inflammatory macrophages, the sections were immunofluorescence-stained with antibodies against INOS (Abcam, ab178945) and CD68 (Abcam, ab955). To stain anti-inflammatory macrophages, the sections were immunofluorescence-stained with antibodies against CD163 (Abcam, ab182422) and CD68 (Abcam, ab955). INOS and CD163 signals\u0026nbsp;were visualized using fluorescein isothiocyanate-conjugated secondary antibodies (Jackson ImmunoResearch Laboratories, West Grove, PA, USA).\u0026nbsp;The CD68 signal was visualized\u0026nbsp;using rhodamine (TRITC)-AffiniPure goat anti-mouse IgG (Jackson ImmunoResearch Laboratories). The sections were counterstained with DAPI and examined via fluorescence microscopy (DFC 3000\u0026nbsp;G, Leica).\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Stretchable, Implantable, Biocompatible, Organic Field-Effect Transistor, E-skin, Medical rubber, Logic gate, Bioelectronics","lastPublishedDoi":"10.21203/rs.3.rs-4844804/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4844804/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eImplantable bioelectronics transforms the interface between electronics and biological systems, enabling continuous \u003cem\u003ein situ\u003c/em\u003e monitoring and modulation of electrophysiological signals. A critical challenge remains in the mechanical mismatch between conventional rigid electronic components and soft biological tissues, which can lead to tissue damage and inflammation. Additionally, the low biocompatibility of existing soft electronic components exacerbates these issues. Here, we present biocompatible, elastomeric organic field-effect transistors (OFETs) designed for implantable applications. These OFETs utilize a blend of semiconducting nanofibers and medical-grade elastomers, such as poly[(dithiophene)-alt-(2,5-bis(2-octyldodecyl)-3,6-bis(thienyl)-diketopyrrolopyrrole)] (DPPT-TT) and bromo butyl rubber (BIIR), respectively. This composite film exhibits exceptional mechanical stretchability and biocompatibility with similar Young\u0026rsquo;s modulus with human tissues, maintaining high electrical performance even under 50% strain. In addition, the integration of biocompatible dual-layer Ag-Au metallization results in robust, stretchable, and corrosion-resistant electrodes. \u003cem\u003eIn vitro\u003c/em\u003e assessments with human dermal fibroblasts and macrophages confirmed the biocompatibility of the materials, showing no adverse effects on cell viability, proliferation, or migration. \u003cem\u003eIn vivo\u003c/em\u003e implantation studies in BALB/C mice revealed no significant inflammatory response or tissue damage, underscoring the potential for long-term biointegration. Our biocompatible and stretchable OFETs demonstrated stable operation in logic circuits, including inverters, NOR, and NAND gates under physiological conditions, offering a promising platform for various medical applications, from diagnostics to therapeutic interventions.\u003c/p\u003e","manuscriptTitle":"Biocompatible Elastomeric Transistors for Implantable Bioelectronics","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-06 03:31:42","doi":"10.21203/rs.3.rs-4844804/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-electronics","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"natelectron","sideBox":"Learn more about [Nature Electronics](http://www.nature.com/natelectron/)","snPcode":"","submissionUrl":"","title":"Nature Electronics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Research","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"227208f5-d1ca-4a8b-a116-b5e0268ec6bd","owner":[],"postedDate":"September 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":36745790,"name":"Physical sciences/Materials science/Materials for devices/Electronic devices"},{"id":36745791,"name":"Biological sciences/Biotechnology/Nanobiotechnology/Bionanoelectronics"},{"id":36745792,"name":"Biological sciences/Immunology/Cell death and immune response"}],"tags":[],"updatedAt":"2025-09-03T07:11:24+00:00","versionOfRecord":{"articleIdentity":"rs-4844804","link":"https://doi.org/10.1038/s41928-025-01444-9","journal":{"identity":"nature-electronics","isVorOnly":false,"title":"Nature Electronics"},"publishedOn":"2025-09-02 04:00:00","publishedOnDateReadable":"September 2nd, 2025"},"versionCreatedAt":"2024-09-06 03:31:42","video":"","vorDoi":"10.1038/s41928-025-01444-9","vorDoiUrl":"https://doi.org/10.1038/s41928-025-01444-9","workflowStages":[]},"version":"v1","identity":"rs-4844804","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4844804","identity":"rs-4844804","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}