Advanced Materials Technologies

Two-photon polymerization (2PP) enables fabrication of hydrogel constructs with submicron, cell-scale resolution, but hydrogel-based bioinks are markedly more sensitive to process variability than conventional photoresists, and this sensitivity is further amplified when living cells are embedded in the resin. Post-processing evaluation, performed only after development, occurs too late to enable any corrective action. A full-factorial design of experiments across laser power and scan speed shows that fabrication outcome depends on both parameter choice and cell presence, with cells shifting and broadening the range of conditions yielding structurally sound constructs. However, substantial variability persists within each nominal condition and cannot be resolved by parameter refinement alone, indicating that outcome is governed by what occurs during each individual print rather than by the parameters set. To capture this, a layer-wise polymerization score is derived from pairwise comparisons of same-layer coaxial images, grounded in the psychophysics of relative judgment, and assembled into a Layer-wise Image Trajectory (LIT) for each print. Applied to both acellular and cell-laden formulations, LIT curves separate cleanly by post-processing outcome without any outcome label used in training, showing that fabrication quality can be predicted early in the build. Building on this signal, individual LIT curves are compared against statistical control limits derived from confirmed successful prints, enabling early detection of anomalous fabrication behavior at early-to-mid layers, well before development. To the best of the authors knowledge, this is the first application of in situ quality prediction and anomaly detection to cell-laden two-photon polymerization.

Biochemical gradients and mechanical microenvironments synergistically regulate tumor cell proliferation, migration, and phenotypic evolution, which are critical for recapitulating in vitro tumor physiological microenvironments. In this work, a multilayer-assembled microfluidic chip integrated with Tesla-valve flow channels was developed for 3D SKOV3 cell culture under combined biochemical gradients and mechanical stiffness interfaces. The reconfigurable multilayer PMMA structure enables flexible construction of diverse concentration gradient fields, while the embedded Tesla-valve geometry effectively stabilizes fluid flow, reduces flow velocity fluctuation, and generates smoother, more stable biochemical gradients compared with conventional curved channel designs. Multiphysics simulations were performed to systematically verify the flow field distribution and gradient formation performance of the optimized channel structure. Furthermore, by constructing heterogeneous hydrogel microenvironments consisting of rigid Pluronic F127 and soft dextran hydrogel inside microfluidic chambers, stable mechanical stiffness interfaces were successfully fabricated. Combined with TGF {beta}1 biochemical stimulation, the platform was applied to explore the durotactic migration and morphological changes of 3D-cultured SKOV3 cells at stiffness interfaces. Fluorescence staining results demonstrated that mechanical boundary conditions significantly affected cell migration behavior and cell aggregation phenotypes under consistent biochemical induction. With the advantages of low cost, simple assembly, good biocompatibility, and controllable dual physicochemical microenvironments, this multilayer microfluidic platform provides a reliable and efficient strategy for in vitro tumor microenvironment simulation and tumor cell mechanobiology research.

Digital micromirror device (DMD)-based bioprinting enables high-resolution fabrication of hydrogel-based tissue constructs, but print fidelity and hydrogel mechanics are typically coupled through polymer concentration, light exposure, and crosslinking density. This creates a materials constraint for vascular bioprinting, where constructs must preserve microscale architecture during fabrication while supporting multicellular remodeling, lumen formation, and long-term tissue organization. To meet these requirements, we developed a 4D GelMA-Cad/gelatin hydrogel with time-dependent mechanics that maintains print fidelity while providing a soft, cell-permissive matrix. GelMA-Cad provides a covalently photocrosslinked, bioactive network containing an N-cadherin-mimetic peptide, while uncrosslinked gelatin serves as a transient matrix-modifying component that diffuses from the hydrogel after fabrication, producing further softening without bulk degradation of the GelMA-Cad network. We characterized hydrogel chemistry with NMR, quantified time-dependent changes in stiffness, visualized pore morphology with cryo-SEM, and evaluated the platform in retinal and pulmonary constructs. The 4D hydrogel supports 3D-patterned accuracy, cell viability, inner blood-retinal barrier vasculature, and vascularized lung-alveolar tissue models. Single-cell RNA-sequencing of the pulmonary vascular-alveolar model demonstrated compartment-specific transcriptional responses, including enrichment of lung capillary-associated endothelial features and AT1-like epithelial states. Overall, this platform decouples DMD print fidelity from post-print matrix mechanics for vascularized soft tissue bioprinting and tissue modeling.

Photovoltaic subretinal prosthesis, PRIMA, provides central vision to patients blinded by age-related macular degeneration, with acuity matching the 100 m pixel size. Further miniaturization requires pillar electrodes to position the stimulating surfaces closer to the inner retinal neurons. While such structures can be electroplated in gold and coated on their tops with SIROF, the exposed gold sidewalls are not biocompatible. Sputtering or atomic layer deposition of protective coatings are unsuitable for selectively passivating the pillar structures without also coating the photosensitive regions and return electrodes of the implant. Here, we present a strategy for biocompatible coating of pillar sidewalls while preserving surrounding implant functionality. The approach combines non-critical photoresist lithography to protect planar return electrodes with electrodeposition of TiO2; or Pt onto gold pillar sidewalls. In-vivo studies demonstrated that both TiO2 and Pt coatings are biocompatible and prevent adverse reactions of the retinal tissue to gold. Since specific capacitance of electroplated TiO2 (25 F/cm2) is much lower than that of Pt (240 F/cm2), the former better limits the current from the side walls and ensures that charge injection occurs predominantly through the pillar tops coated with SIROF (~6 mF/cm2). Electrodeposition, combined with noncritical photolithography provides a scalable wafer-level solution for fabrication of biocompatible three-dimensional electro-neural interfaces, addressing a critical bottleneck in bioelectronics.

Extrusion bioprinting requires simultaneous control of material processability, rapid post-deposition stabilization, geometric fidelity, and cell compatibility. Here, we defined an experimental biofabrication window for three visible-light photocrosslinkable protein formulations based on silk fibroin (SF), gelatin methacryloyl (GelMA), and collagen methacryloyl (ColMA) using a extrusion-bioprinting workflow and ruthenium/sodium persulfate (Ru/SPS) photochemistry. Material-specific photocrosslinking conditions were first established under 430-nm irradiation and subsequently evaluated by ATR-FTIR spectroscopy, unconfined compression, short-term ARPE-19 cytocompatibility, and printing assays. Stable bulk hydrogels were obtained using 1-Ru/SPS, 45 mW, and 5 min for SF; 2.5- Ru/SPS, 45 mW, and 7 min for GelMA; and 2.5- Ru/SPS, 45 mW, and 6 min for ColMA. The selected formulations formed compliant hydrogels with initial compressive moduli of 0.60, 0.52, and 2.55 kPa for SF, GelMA, and ColMA, respectively, without significant differences among groups. Short-term XTT assays identified the unreacted Ru/SPS-containing precursor as a major biological constraint, whereas photoinitiator-free SF and GelMA maintained metabolic activity close to the culture-medium reference. GelMA and SF generated interconnected lattices with printability indices of 0.893 and 0.963, respectively. Detailed SF analysis showed high positional accuracy (96.9%) despite substantial post-deposition spreading, demonstrating that positioning accuracy and dimensional fidelity are distinct properties. Cell-laden printing was achieved with both SF and GelMA, and independent extrusion testing showed no statistically significant reduction in short-term ARPE-19 viability after SF bioprinting. Following the complete printing and photocrosslinking workflow, both formulations contained predominantly viable cells, but only SF retained the printed grid-associated cellular architecture under the tested conditions. These findings support the concept that biofabrication performance is an operational property arising from the intersection of photocrosslinking, cytocompatibility, extrusion compatibility, geometric fidelity, and post-fabrication structural stability.

Synthetic optical skin models offer reproducible, tunable optical properties but lack biological responsiveness, while tissue engineered skin models provide cellular authenticity but suffer from optical variability and limited controllability. The growing demand for alternatives to animal models in the development and validation of optical biomedical technologies highlights the need for a new class of test system that combines the strengths of both approaches while addressing their respective limitations. Here, we introduce the concept of a modular biohybrid skin model, a new testing concept that integrates an optically defined artificial epidermal layer, incorporating polydopamine nanoparticles for changes in skin tone, with living human keratinocytes in two and three-dimensional configurations. In the Optical Protection Model, UV-B-induced apoptosis in primary keratinocytes is quantitatively modulated by model pigmentation level, demonstrating a relationship between optical attenuation and caspase 3/7 activity across three artificial skin tone conditions. In a Structured Dermal Model, keratinocytes seeded onto a hydrogel scaffold localize within follicle-like microcavities, as confirmed by live/dead staining and confocal z-stack imaging. Together, these experiments lead to a new category of test system in the space between inert optical models and variable tissue models that may contribute to reducing the reliance on animal models in biomedical optics.

Microfluidics-assisted encapsulation of cells in hydrogel microbeads has found diverse applications in tissue engineering, disease modelling, and drug testing. However, upscaled production of submillimeter-sized microbeads, each encapsulating optimally tens to hundreds of living cells, remains a challenge. Excessive viscous stresses or non-homogeneous crosslinking reactions hamper droplet monodispersity, hydrogel integrity, and/or cell viability. Herein, we present a device consisting of (i) tens of parallel step-emulsifiers arranged radially around the hydrogel inlet and (ii) an in-flow UV crosslinking system capable of continuous generation and crosslinking of up to around 45000 microbeads/min, each encapsulating N~50 cells, at cell viability exceeding 80%. We use gelatin methacryloyl (GelMA) as the biomaterial of choice and establish a unique sweet spot in terms of UV wavelength, irradiance, and exposure time- the latter controlled via the net applied flow rate and the length of the UV-exposed microchannel- at which we achieve an optimal balance between long-term microbead stability and cell viability. In particular, we observe a strong correlation between reduced cell viability and poor crosslinking efficiency, the latter attributed to the presence of a spontaneous core-shell structure. We further study the impact of added methacrylated hyaluronic acid (HAMA) and extracellular matrix (ECM) on cell proliferation and microtissue formation in the case of triple-negative breast cancer (TNBC) cells for future application in drug testing. The upscaled production of the encapsulated microtissues demonstrated here provides new perspectives for both drug testing and cell therapies where the precision in microenvironment formulation as well as production throughput remain of primary importance.

Photocrosslinkable gelatin derivatives are promising bioinks for soft tissue engineering, but their use in cell-laden digital light processing (DLP) requires a balance between tunable mechanics, printability and cytocompatibility. Here, we report a small library of photocrosslinkable gelatin-based precursor formulations for cell-laden DLP, with the broader aim of generating a versatile platform for soft tissue engineering rather than a formulation restricted to one tissue model. A bifunctional methacryloyl-norbornene gelatin (GelMANB) was developed to combine methacryloyl chain-growth polymerisation with norbornene-mediated thiol-ene crosslinking and was benchmarked against gelatin methacryloyl (GelMA). GelMANB formulations containing different thiolated crosslinkers were evaluated to determine the influence of crosslinking chemistry as well as polymer concentration on network formation and physico-chemical properties. Thiol-ene formulations enabled broad tuning of hydrogel stiffness and exhibited rapid photocrosslinking, while crosslinker selection further influenced swelling and tensile behaviour. Selected GelMANB/dithiothreitol (GelMANB/DTT) and GelMANB/thiolated gelatin (GelMANB/GelSH) formulations were subsequently processed via DLP alongside GelMA. Optimised exposure conditions enabled reproducible fabrication of porous scaffolds that retained dimensional stability under osmotic pressures relevant to several soft tissues. Following cell-laden printing, human foreskin fibroblasts remained viable after seven days, reaching 95.0{+/-}5.9% viability in GelMANB/DTT and 94.9{+/-}2.7% in GelMANB/GelSH, compared with 87.2{+/-}6.0% in GelMA. In 2-mm-thick hydrogel discs, GelMANB/GelSH supported the most sustained fibroblast elongation, reaching 30.9{+/-}6.3% elongated cells at day 7, although elongated cells were mainly confined to the outer surface layers. Porous scaffolds with 400 m struts and 1.3 mm pores reduced the characteristic hydrogel thickness and enhanced elongated morphology across all formulations, highlighting GelMANB as a modular platform for cell-laden soft tissue biofabrication.

Myocardial infarction highlights an urgent need for strategies to regenerate functional cardiac tissue. Cardiac tissue engineering offers a promising approach; however, fabricating scaffolds that simultaneously integrate precise architectural anisotropy, mechanical compliance, and electrical conductivity remains an open challenge. In this work, we utilized melt electrowriting (MEW) to construct well-defined, 20-layer anisotropic rhomboidal polycaprolactone (PCL) scaffolds. We characterised them by tensile testing and by micro- and nanoscale microscopy. While introducing electrical conductivity via bulk blending with fillers (polypyrrole (PPy), polyaniline, or graphene oxide) compromised MEW print fidelity and failed to achieve physiological conductivity, surface coating strategies effectively combined conductivity from structural mechanics. Electrical and mechanical testing revealed that gold sputter coating and in situ PPy polymerization both imparted robust electrical conductivity while preserving the microfibrous architecture. However, when seeded with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in fibrin hydrogels, only the gold-coated scaffolds supported synchronized, robust, and sustained contractile activity. PPy-coating resulted in functionally restricted constructs, suggesting that excessive structural rigidity limited tissue deformability. Gene expression analysis further revealed that elevated electrical conductivity alone does not drive hiPSC-CM maturation. Our data indicates that successful cardiac patch design relies on the integrated optimization of mechanics and architecture rather than treating conductivity as an isolated parameter, offering foundational guidelines for developing translational bioengineered heart patches.

Carbon is a versatile electrode material that is used in applications ranging from electrical energy storage and electrosynthesis to CO2 conversion, H2 production, and biosensing. The development of pyrolytic carbon electrodes derived from lithographically patterned photoresist structures has expanded the possibilities for creating diverse 2D and 3D electrode designs. In this paper, we present disc-shaped SU-8-derived pyrolytic carbon scaffold electrodes with an open hexagonal honeycomb lattice. The scaffolds were fabricated, using embedded 3D printing within a shear-thinning support bath composed of fused silica nanoparticles (7% w/v) in mineral oil. The rheological properties of the support bath were optimized to enable the printing of low-viscosity materials like SU-8, which would otherwise lack structural integrity in standard extrusion-based 3D printing. The SU-8 scaffolds were then pyrolyzed and characterized using SEM, Raman spectroscopy, Energy Dispersive X-ray, X-ray Photoelectron Spectrometry, and Transmission Electron Microscopy, which revealed graphene-like 'microflowers' on its surface. Electrochemical analysis demonstrated excellent electrochemical properties. The functionality of the scaffold electrodes was validated by differentiation of human neural stem cells into dopaminergic neurons on the scaffold surface, followed by real-time detection of dopamine exocytosis upon cell depolarization.

Transdermal biosensing and drug delivery provide convenient, pain-free, and user-friendly solutions for personalized therapy. However, challenges remain in detecting and treating acute diseases, primarily due to current limitations in effective detection of transdermal biomarkers and administration of therapeutics to an individual within a short time window in a real-world environment. Here, we integrate a compact acoustofluidic patch for transdermal sampling, sensing, and delivery in a rapid and automated manner. By leveraging acoustic streaming and 3D-printed microfluidic designs, acoustofluidic sampler and injector modules are assembled for penetration of the skin stratum corneum, precise sampling of skin interstitial fluids, and controlled percutaneous release of therapeutics, respectively. By incorporating an electrochemical sensing module, the integrated patch can be further developed to achieve in situ and rapid detection of transdermal biomarkers and automated transdermal delivery of therapeutics via closed-loop control. As a proof-of-concept application, we demonstrate our approach can detect and reverse life-threatening acute allergic reactions in a mouse model of anaphylaxis by rapid sampling and sensing transdermal histamine followed by automated transdermal delivery of epinephrine. The innovative acoustofluidic patch may enable a new kind of transdermal devices for personalized therapy of various acute diseases.

Angiogenesis following injury has been shown to be driven by fibrillar proteins of the extracellular matrix (ECM), such as collagen. However, the use of protein-based biomaterials presents some challenges, such as uncontrolled degradation and limited tuneability. We demonstrate how to create patterned interpenetrating networks (IPNs) based on covalently crosslinked alginate and physically crosslinked collagen that provide suitable mechanical properties to support migration of endothelial cells (ECs) in a spatially controlled manner. Low molecular weight alginate is functionalized with norbornene (N) or tetrazine (T), which enables two independent covalent crosslinking methods: UV-mediated and degradable crosslinks with matrix metalloproteinase (MMP) sensitive peptides (Deg) and slower spontaneous N:T non-degradable crosslinks (noDeg). Using photolithography, patterns in degradation, collagen fibrillogenesis, microarchitecture and matrix viscoelasticity are created. The potential of such 3D patterned alginate-collagen (Alg-Col) IPNs to spatially guide EC invasion and proliferation was tested in a microfluidics platform resembling an early healing setting. Only regions combining collagen fibrillogenesis, alginate degradability and viscoelasticity demonstrated EC cell invasion similar to the ones found in vivo following injury. The 3D patterned Alg-Col IPNs are compatible with microfluidics, offer an strategy to widen the applications of protein-based hydrogels and present a versatile platform for tissue engineering and disease modeling.

Four-dimensional (4D) materials incorporating functional gradient designs offer a powerful platform for engineering dynamic structures capable of programmed shape transformations in response to environmental stimuli. However, most gradient-based 4D systems rely on uniaxial gradients, which typically generate simple, symmetric deformations with uniform curvature, limiting their ability to recreate biomimetic architectures that require spatially coordinated morphogenesis. Here, we report a biaxial gradient-engineered 4D hydrogel system capable of programmable, non-uniform shape morphing within a single construct. A one-step photocrosslinking strategy integrates vertical light attenuation and horizontal grayscale photomask patterning to establish orthogonal crosslinking gradients along two directions, producing spatially heterogeneous swelling stresses that drive controlled multi-directional deformation. The resulting hydrogels exhibit tunable swelling and mechanical properties, enabling precise regulation of curvature distribution and shape transformation. This biaxial gradient platform generates diverse biomimetic architectures, including swan-neck, fiddlehead fern, sea star, and Euonymus europaeus-like structures. Importantly, the system supports cell-laden biofabrication, where human mesenchymal stem cell-encapsulated constructs maintain high viability and undergo chondrogenic differentiation while preserving programmed morphologies. This work establishes biaxial gradient-programmed 4D hydrogels as a robust strategy for integrating morphogenesis with tissue formation, advancing biomimetic biofabrication and morphogenetic tissue engineering.

Capillaric circuits (CCs) enable pre-programmed liquid handling through self-filling and passive valving governed by capillary forces, eliminating the need for external pumps and actuators. However, CCs optimized for high cohesion liquids (HCL) such as water are intrinsically unsuitable for programmed flow control of low cohesion liquids (LCL) such as oils and solvents because the high surface free energy needed for capillary flow of HCL results in uncontrolled, complete wetting by LCL. Here, we introduce a library of multiphase components including phase-to-phase valves (P2PV), hydro-pneumatic relays (HPR) and multiphase domino valves (MDVs) that collectively enable CCs to concomitantly process HCLs and LCLs. P2PVs use a pre-filled HCL to valve immiscible LCLs (e.g. oil) by confining the LCL, and upon triggering, hydraulically entrain it. To prevent uncontrolled mixing between miscible LCLs (e.g. ethanol) and the HCL, HPRs with an air gap and air waste are added to the P2PV. MDVs are further added and enable preprogrammed, sequential delivery of LCL and HCL by multiphase microfluidic chain reactions. Multiphase liquid processing is applied to automated, on-chip lipid nanoparticle (LNP) manufacturing, illustrating the potential of multiphase CCs.

Type II photoinitiators are essential for numerous applications, including advanced 3D printing techniques such as Xolography. Despite offering tunable wavelengths and reaction mechanisms, their limited photoreactivity hinders widespread adoption. Solutions to increase reactivity, particularly in aqueous solutions and in a biocompatible manner, are urgently needed. Here, we report the surprising finding that iodixanol enhances reactivity of type II photoinitiation systems. Supplementing Xolographic print resins with iodixanol increases photoreactivity, which reduces print times and light dosage tenfold, and enables printing of previously unprintable material formulations. Surprisingly, iodixanol supplementation also improves cell viability in a dose-dependent manner, while reducing cell-mediated light scattering. Together, this enables accurate Xolographic printing of highly cell-dense bioresins, which facilitated the biofabrication of engineered living matter with up to 100 M cells mL-1 (>40% cells by volume) with a resolution of ~65 microns. These advances enabled the first demonstration of tissue function in Xolographically-printed materials. Human induced pluripotent stem cell-derived cardiomyocytes were printed into contractile cardiac-like engineered living matter, which exhibited enhanced cell-cell contact and synchronous contractions, confirming tissue level function. As a highly water soluble, cytocompatible, and clinically approved compound, iodixanol therefore represents a valuable and translatable solution to improve the reactivity of type II photoinitiation systems, which enables volumetric biofabrication of highly cell dense living matter. This unlocks a new role for iodixanol in a wide variety of fields including dentistry, chemistry, organic photovoltaics, tissue engineering, and 3D printing.

Gelatin methacrylate (GelMA) hydrogels offer many advantageous properties such as excellent biocompatibility, tunable stiffness, and rapid fabrication, making them attractive materials for neural systems-on-a-chip devices used to study axonal outgrowth in three-dimensional (3D) environments. In this study, we evaluate properties of GelMA hydrogels crosslinked with visible blue light and application of these hydrogels for encapsulation of primary dorsal root ganglion (DRG) explants inside a custom microscale device. We selected low GelMA polymer concentrations of 3 % and 6 % w/v for hydrogel preparation to create soft materials and demonstrate the effect of degree of functionalization (DoF) on stiffness of GelMA in a blue light-induced crosslinking system. Additionally, a decrease in crosslinking efficiency and stiffness of GelMA was observed upon reconstitution of the polymer in DMEM cell culture media compared to PBS. To evaluate the axonal outgrowth, DRG explants were encapsulated in various GelMA formulations and cultured for 7 days. Following incubation, the explants were fixed and immunochemically labelled with anti-beta-III-tubulin antibody. We further describe an application of custom-developed semi-automated image analysis tool together with linear mixed effects modeling to evaluate axonal outgrowth across different GelMA formulations. Among the formulations tested in our study, 3 % GelMA 95 % DoF hydrogels supported the longest neurite outgrowth suggesting that matrix properties influenced neurite extension.

Precise control over scaffold microarchitecture is critical for engineering cell-instructive biomaterials and for understanding how structural cues regulate cell-material interactions. In this study, ultrafine cellulose-based scaffolds fabricated by near-collector electroprinting (NCE) were used as a model platform to investigate how scaffold architecture influences the transition between quasi-2D and 3D cell-scaffold interactions. Cellulose acetate scaffolds with micrometer-scale fiber diameters, tunable fiber spacing, and defined multilayer geometries were systematically evaluated to determine the effects of scaffold dimensionality and pore architecture on human mesenchymal stem cell behavior. Low-layer scaffolds functioned primarily as quasi-2D topographical patterns, where cells adhered predominantly to the underlying substrate while aligning along the printed fibers in a spacing-dependent manner. Increasing scaffold height generated a 3D microenvironment that promoted direct cell-scaffold interaction and enabled inter-fiber bridging. Quantitative analysis of nuclear orientation and actin organization revealed that scaffold dimensionality and fiber spacing jointly govern the transition between topographical guidance and bridging-mediated cellular organization. To further demonstrate material versatility, lignosulfonate was incorporated into the printing ink to fabricate composite scaffolds while retaining print fidelity and cytocompatibility. Together, these findings demonstrate how scaffold architecture can be used to govern cell-material interactions across multiple dimensional regimes.

Conducting polymers are widely used in bioelectronic interfaces because of their mixed ionic-electronic conductivity, mechanical compliance, and compatibility with biological systems. However, their electrochemically driven structural dynamics have received little attention as a mechanism for mechanical cell stimulation. Here, we show that electrochemical actuation of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) generates mechanical cues capable of activating endogenous mechanosensitive pathways in HEK293T cells. Transparent PEDOT:PSS films deposited on ITO exhibited a heterogeneous granular morphology and underwent potential-dependent microscopic deformation during electrochemical modulation. Direct optical tracking revealed displacement of the polymer boundary, with structural changes occurring preferentially in polymer-dense regions and propagating toward the film edge. When HEK293T cells were cultured directly on PEDOT:PSS, repeated electrochemical stimulation at -240 mV produced reproducible intracellular Ca2+ responses. Pharmacological inhibition with GsMTx4 attenuated the calcium response, whereas blockade of voltage-gated sodium channels with tetrodotoxin largely preserved it, supporting the involvement of mechanosensitive pathways in the cellular response. These findings identify PEDOT:PSS as an electromechanical biointerface in which electrochemical modulation can introduce a mechanical component alongside the established electrical function of the interface. This mechanical contribution should therefore be considered when interpreting cellular responses to conducting polymer- based electrical stimulation and provides a basis for engineering bioelectronic interfaces that deliberately couple electrical control with mechanotransduction.

Photovoltaic subretinal prostheses replace the lost photoreceptors in patients blinded by atrophic age-related macular degeneration (AMD) and provide central vision by electrically stimulating the inner retinal neurons. Subretinal debris in geographic atrophy separate the inner nuclear layer from the implant by tens of micrometers, increasing the stimulation threshold and reducing the pattern contrast. Absence of this separating layer in animal models diminishes the accuracy of preclinical testing of the next-generation implants, especially with smaller pixels. We developed three-dimensional biomimetic scaffolds nanoprinted onto photovoltaic arrays to provide a precisely controlled separation between the implants and target neurons in animal models of retinal degeneration. Gap sizes of the scaffolds were adjusted to meet the following requirements: they should allow light penetration to the implant, provide unobstructed flow of electric current, but preclude migration of cells into their 3-D structure. Gaps of 3 m were found to be optimal as they restricted cellular migration and maintained the inner nuclear layer above both planar and pillar electrode arrays. Scaffolds did not measurably alter the photovoltaic response and accurately reproduced the distance dependence of stimulation threshold. Following implantation, the initially fluid-filled intra-scaffold space was progressively filled by cellular matter matching the density of the subretinal debris. This transition is expected to increase resistivity of the scaffold to that of tissue, which was evidenced by concurrently improved grating acuity. These results establish a model of the controlled separation between the implant and the target neurons reproducing the features of subretinal debris in geographic atrophy of human patients, thereby providing a platform for accurate preclinical evaluation of the subretinal implants.

Synthetic grafts remain ineffective for small-caliber vascular applications due to thrombosis and intimal hyperplasia. To address these limitations, our lab designed a multilayer graft consisting of a hydrogel coating that promotes post-implantation endothelialization and an electrospun mesh that matches arterial mechanical properties. Damage-resistant hydrogels were engineered using a double-network system composed of polyether urethane diacrylamide and N-acryloyl glycinamide to enhance fracture resistance through hydrogen bonding. In this study, we utilized redox initiation to apply conformal, durable hydrogels to electrospun grafts. Bioactivity wa introduced using streptococcal collagen-like proteins containing 1{beta}1 and 2{beta}1 integrin-binding motifs, enabling selective cell-material interactions that support endothelialization while preserving acute thromboresistance. To establish the feasibility of these grafts as off-the-shelf devices, we evaluated coating integrity and bioactivity retention following sterilization and dynamic physiological loading. Sterilized composites exhibited surgically-associated damage resistance, indicating that sterilization did not compromise hydrogel durability. Coating integrity and bioactivity were also preserved after six weeks of physiological loading. Acut thromboresistance was supported by both static platelet adhesion assays and dynamic whole-blood bioreactor studies using heparinized blood, with low platelet adhesion observed relative to ePTFE. Finally, a pilot ovine carotid model demonstrated successful surgical handling and sustained graft patency. Collectively, these results highlight the promise of multilayer vascular grafts as durable, thromboresistant conduits for small-diameter vascular applications. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=60 SRC="FIGDIR/small/741222v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@14ec910org.highwire.dtl.DTLVardef@17259e8org.highwire.dtl.DTLVardef@6cb611org.highwire.dtl.DTLVardef@1251d7d_HPS_FORMAT_FIGEXP M_FIG C_FIG