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Mechanical cues encoded in the extracellular microenvironment play essential roles in regulating cardiac rhythm and tissue-level coordination; however, systematic interrogation of when mechanical inputs are most effective remains technically challenging. While substrate stiffness and cyclic stretch are widely used to condition cardiomyocytes in vitro, most platforms lack the temporal precision required to probe phase-dependent mechanosensitivity during spontaneous beating. Here, we report a biomaterials-based mechanical stimulation platform that enables real-time, phase-specific delivery of localized stretch to autonomously beating cardiomyocyte aggregates cultured on soft polydimethylsiloxane (PDMS) substrates. By integrating live imaging-based beat detection with piezo-driven microscale actuation, mechanical stimuli were triggered at defined fractions of the intrinsic interbeat interval (IBI), allowing direct comparison of in-phase and out-of-phase mechanical perturbations. Using one-dimensional cardiomyocyte aggregates as a model system, we show that randomly timed mechanical stimulation rarely altered intrinsic rhythm (∼0.3% of beats). In contrast, phase-locked stimulation applied near the end of the contraction-relaxation cycle (∼90% of the IBI) reproducibly induced transient IBI shortening, reversed contraction-wave propagation, and shifted pacemaker activity toward the site of stimulation. Mechanical stimulation delivered at midcycle (∼50% of the IBI) produced minimal effects. Displacement-resolved analysis revealed that phase-specific stimulation redistributed mechanical output within the aggregate: contraction amplitude was maintained or enhanced near the stimulation site while being attenuated in distal regions. These results demonstrate that developing cardiac tissues exhibit narrow temporal windows of mechanical susceptibility and robust resistance to perturbation outside these phases. This platform provides a versatile biomaterials-enabled framework for dissecting dynamic mechano-electrical feedback, optimizing mechanical conditioning strategies, and engineering cardiac tissues with controllable rhythmic properties.

Indwelling medical devices, such as intravenous and urinary catheters, have significantly enhanced patient care and greatly improved treatment outcomes. Despite rapid advances in medical devices, infection and thrombosis continue to pose major challenges to device functionality and integrity. Given that current treatments often involve systemic administration of antibiotics and anticoagulants, there is an urgent need for medical devices that are inherently antibacterial and antithrombotic. We explore the chemical conjugation of the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) with the fluoroquinolone-based, broad-spectrum antibiotic Ciprofloxacin (CIP). The combination strategy integrates the directed antibacterial activity of CIP with the antithrombotic and antibiofilm properties of NO. Furthermore, the conjugate molecule (SNAP-CIP) was incorporated into silicone rubber (SR) for catheter fabrication (SR-SNAP-CIP). SR-SNAP-CIP demonstrated NO-release for 14 days while remaining biocompatible. The NO release allowed SR-SNAP-CIP to reduce platelet adhesion in vitro by ∼45%. The dual-action material exhibited antibacterial properties when tested in vitro for bacterial adhesion (24 h and 14-day CDC bioreactor), planktonic viability, and biofilm biomass accumulation against S. aureus, and E. coli. To assess bacterial migration across the skin barrier, an ex vivo skin translocation model was performed, which showed no bacterial migration on the SR-SNAP-CIP catheter. After the 14-day in vivo rabbit catheter model, SR-SNAP-CIP showed a significant reduction (∼84%) in thrombus area on the catheter and surrounding vein. Furthermore, SR-SNAP-CIP catheters showed a 92% reduction in adhered S. aureus. Overall, SR-SNAP-CIP demonstrated a combination of technologies, harnessing the antibacterial potential of CIP and the antibiofilm and antithrombotic properties of NO. STATEMENT OF SIGNIFICANCE: Despite advancements in biomaterial design, catheter-associated thrombosis and infection persist as primary drivers of device failure and patient morbidity, highlighting the critical need for dual-functioning anti-thrombogenic and antimicrobial interventions. Materials capable of addressing both challenges simultaneously are vital to the development of next-generation, hemocompatible catheter biomaterials. In this work, we present the incorporation of a nitric oxide (NO)-releasing ciprofloxacin conjugate molecule into a polymer platform to achieve extended NO release and robust antiplatelet activity. The resulting platform demonstrated antibacterial performance in vitro, while remaining cyto- and hemo-compatible. Furthermore, these antibacterial and antithrombotic effects were sustained in a 14-day in vivo rabbit catheter model, indicating strong potential for clinical translation.

Wearable fabrics embedding crystalline semiconductor materials (e.g. germanium, silicon) are promising biomedical devices for their therapeutic potential in musculoskeletal disorders, including osteoarthritis, tendinopathies, and chronic pain, and for supporting tissue healing and regeneration. These fabrics exert their bioactive functions without applying mechanical pressure or drug delivery systems, offering a non-invasive and comfortable therapeutic alternative that operates through mild thermal stimuli at body temperature. Recent peer-reviewed literature on semiconductor-based wearable textiles, far-infrared-emitting biomaterials, bioelectric signalling in tissue repair, and their clinical application in musculoskeletal disorders. At body temperature, semiconductor-containing fabrics consistently emit far-infrared radiation, experimentally associated with improved microcirculation and modulation of inflammation. Limited clinical studies report improvements in pain and functional outcomes in chronic musculoskeletal conditions, with good tolerability during prolonged wear. Proposed mechanisms include thermally induced electron release, ion generation, and piezoelectric or piezoresistive activity during movement, but direct biological evidence remains limited. The specific contribution of far-infrared emission is difficult to distinguish from thermal or placebo effects. Advances in bioelectric signalling research and textile engineering provide a framework to investigate electroactive interactions between semiconductor fabrics and biological tissues. Well-designed randomized trials, quantitative characterization of emitted physical stimuli, and mechanistic cellular studies are needed to establish clinical efficacy and inform regulatory classification.

While natural infections expose the immune system for days to weeks of inflammation and antigen presentation, immunizations with conventional bolus vaccines often lead to rapid clearance of antigens and adjuvants. Prolonged exposure to vaccines using controlled delivery devices or repeated dosing regimens has been shown to enhance germinal center reactions, leading to improved humoral responses, including increased magnitude of antibody titers and enhanced neutralizing activity. Herein, we report the use of injectable polymer-nanoparticle (PNP) hydrogels as a vaccine depot technology for sustained delivery of the clinically relevant SARS-CoV-2 Hexapro subunit antigen and a toll-like receptor agonist adjuvant. In mice, we demonstrated that PNP hydrogel vaccines enhanced germinal center responses and antibody responses relative to bolus vaccination. In nonhuman primates, hydrogel vaccines induced enhanced and durable antibody responses against wildtype and variants of concern such as Omicron BA.5 compared to bolus vaccination. We report the first use of a biomaterials-based approach for sustained delivery of vaccines in nonhuman primates, further advancing toward clinical translation.

Although muscle regeneration capacity is remarkable, under some conditions, such as extensive muscle damage or muscular dystrophies, it may be insufficient, leading to impaired muscle repair and deficits in its structure and function. Among the treatments considered for such conditions are those combining the use of biomaterials, cells, and the addition of selected factors. In the current study we for the first time evaluated potential in vivo effects of hydrogels designed by us, based on RADA16-I hydrogel and modified with IL4 or SDF1 mimicking peptides, as well as verified whether such effects depend on the environment of skeletal muscle, i.e. acutely injured or dystrophic, i.e. chronic one. Since induced pluripotent stem cells (iPSCs) and their derivatives are considered for dysfunctional skeletal muscle therapies, we injected muscles with hydrogels only or with hydrogels and myoblasts derived from human iPSCs (hiPSCs). We found that hydrogels functionalized with SDF1 or IL4 mimicking peptides were successfully engrafted in injured muscles, and that peptide presence had a significant, supporting effect on muscle regeneration manifested by improved treadmill outcome, as well as enhanced expression of myogenesis, angiogenesis, and neurogenesis markers. In the acute injury model, these effects were elevated after co-injection of hydrogels and hiPSC-derived DMD myoblasts. An increased expression of markers of myogenesis, neurogenesis, and angiogenesis was also observed in dystrophic muscles, but only after treatment with an SDF1 functionalized hydrogel. In such an environment, transplanted cells were rapidly removed, so their injection had no influence on observed effects. The muscle environment (acute injury versus dystrophic/chronic) was crucial for the final outcome of hydrogel transplantation, injected alone or with hiPSC-derived myoblasts. This outcome was beneficial but significantly different in both models.

This study evaluated immunohistochemical profiles associated with guided bone regeneration (GBR) using collagen membranes with different thickness-related mechanical properties to characterize membrane-related biological responses during lateral bone augmentation. Standardized mandibular defects in beagle dogs were grafted with bone substitutes and covered with one of two collagen membranes with different thickness-related mechanical properties or left uncovered. At 8 and 16 weeks, tissues were analyzed for markers associated with osteogenesis (ALP), vascular/perivascular and myofibroblast-associated responses (α-SMA), inflammation-related cell profiles (iNOS and CD206), and bone remodeling (TRAP, Cathepsin K, and collagen type I). At 8 weeks, the FM group showed a trend toward higher numbers of CD206-positive cells in the coronal region. iNOS-positive cells did not differ significantly among groups in any region. However, most macrophage-related outcomes were not statistically significant. The SM group exhibited significantly greater collagen type I deposition, particularly in deeper regions, although this appeared to represent early unmineralized matrix rather than enhanced bone formation. TRAP-positive cells were more frequently observed in membrane-covered groups at both time points, mainly around biomaterials, suggesting remodeling-related activity. ALP, α-SMA, and Cathepsin K showed no significant intergroup differences. At 16 weeks, most immunohistochemical differences had diminished across all groups. Collagen membranes with different thickness-related mechanical properties were associated with distinct early tissue responses during GBR healing. The FM group showed trends toward increased CD206-positive cells, whereas the SM group exhibited greater early collagen type I deposition. Because most inflammation-related outcomes were not statistically significant, these findings should be interpreted cautiously and considered exploratory.

Bone defects caused by trauma, congenital disorders and degenerative diseases such as osteoporosis remain a major clinical challenge, especially in developing regions. Although bone grafting is the current gold standard for treating bone defects, it faces limitations, including donor site morbidity, limited availability and immune rejection. This study developed and evaluated a novel hybrid biomaterial composed of bovine β-lactoglobulin fibrils (BLGFs), oxidized dextran (ODEX) and collagen (COL) extracted from Chambo tilapia fish skin for bone tissue engineering applications. BLGFs were synthesized from whey protein, while ODEX was produced by oxidizing dextran. Three biomaterials-COL, BLGFs/ODEX and BLGFs/ODEX/COL-were synthesized and characterized using Fourier-transformed infrared (FTIR), scanning electron microscope (SEM), and X-ray diffraction (XRD). Cytocompatibility and haemocompatibility were assessed through MTT and haemolysis assays using rat red blood cells. Osteogenic potential was evaluated by Alizarin Red staining after culturing rat bone marrow stem cells in osteoinduction media. The BLGFs/ODEX/COL hydrogel exhibited better porosity, biocompatibility and mechanical stability. SEM and MTT results confirmed robust cell adhesion, spreading, and viability, while haemolysis rates remained below 5%. Enhanced calcium deposition in rBMSCs indicated strong osteogenic differentiation. These results demonstrate that the BLGFs/ODEX/COL hydrogel is a promising, affordable, and biocompatible scaffold for bone tissue regeneration.

Vanillin is among the most widely used flavour compounds in the global food system, valued for its sensory attributes, chemical stability and long history of safety. This review examines emerging evidence that vanillin can be repurposed as a functional bioactive, with a focus on its roles in oxidative stress modulation, immune regulation and ulcer treatment. We place vanillin within a food-to-function framework, linking its chemical properties to biological activity and downstream biomedical applications. Owing to its amphiphilic molecular structure, vanillin can interact with reactive oxygen species, cellular membranes and polymeric matrices, providing a basis for its incorporation into functional formulations. Studies have reported antioxidant and anti-inflammatory effects, synergistic interactions with selected antimicrobial agents and, more recently, the use of vanillin in biomaterials designed to support extracellular matrix organisation and wound closure in chronic and non-healing wounds. Collectively, the available evidence indicates that vanillin possesses multifunctional biological activities that extend beyond its traditional role and support its potential application in wound-healing and tissue-regenerative strategies. This review highlights that the combination of antioxidant, immunomodulatory and biomaterial-compatible properties makes vanillin a promising candidate for incorporation into next-generation therapeutic formulations. Despite these advances, a key limitation remains the lack of comprehensive and standardised in vitro and in vivo evaluation of vanillin-based formulations. Addressing these gaps is essential to define structure-function relationships, validate safety and efficacy, and advance clinical translation. Current vanillin is positioned as a promising link between food-derived compounds and biomedical applications, although further mechanistic and translational studies are needed before clinical use.

Resorbable biomaterials are being developed as alternatives to traditional medical fillers for musculoskeletal repair. However, current materials fail to provide stable wound sealing and tissue regeneration due to inadequate conformal adaptability to irregular defects, weak adhesion in wet environments, and insufficient mechanical robustness balanced with biodegradability. Here, we present iHEÄLS, a transformative, shape-adaptive biomaterial inspired by Play-Doh, composed of cellulose nanocrystal (CNC)-based triple-networks. The interactions among the triple-networks enable conformal defect filling, robust tissue adhesion, and shape stabilization through self-healing. Mechanical training after crosslinking reinforces the network through aligned polymer chains and uniformly oriented CNC. As a biodegradable extracellular matrix, iHEÄLS promotes cell migration and osteogenic differentiation by leveraging nanomaterial incorporation and post-crosslinking mechanical training to amplify bioactivity and mechanotransduction signaling. Additionally, iHEÄLS demonstrates enhanced hemostasis by quickly absorbing biofluids while maintaining malleability, facilitating effective mixing with autologous bone fragments, and promoting bone regeneration in a critical-sized calvarial defect model. Overall, iHEÄLS integrates post-crosslinking mechanical-biological modulability with user-friendly handling, providing a practical platform for musculoskeletal repair in emergencies.

The use of digitally fabricated esthetic crowns for restoring primary molars has increased with the development of CAD/CAM systems, three-dimensional (3D) printing, and tooth-colored biomaterials. However, the available evidence remains heterogeneous, and the clinical role of customized digital crowns in comparison with conventional pediatric crowns is still unclear. This systematic review aimed to assess the available in vitro and clinical evidence on esthetic customized crowns fabricated using digital workflows for primary molars. A systematic literature search was conducted in PubMed, Scopus, and Web of Science to identify studies evaluating digitally fabricated esthetic crowns for primary molars. Eligible studies included in vitro investigations, clinical studies, randomized clinical trials, and finite element analyses assessing marginal or internal adaptation, fracture resistance, wear behavior, clinical performance, gingival health, or patient and parent satisfaction. Risk of bias was assessed using RoB 2 for clinical trials and the QUIN tool for in vitro studies. Due to heterogeneity in study designs, materials, comparators, and outcomes, a qualitative synthesis was performed. Twenty-four studies were included, 17 in vitro studies, six clinical studies, and one finite element analysis. Most studies evaluated zirconia, 3D-printed resins, PMMA, CAD/CAM composites, or hybrid ceramics. In vitro findings suggested favorable marginal and internal adaptation for several customized digital crowns and material-dependent fracture resistance. Clinical studies reported acceptable short-term performance, although follow-up was generally limited and outcomes varied across materials. Stainless steel crowns remained a highly predictable comparator, while esthetic digital crowns showed potential advantages in esthetics and customization. Digitally fabricated esthetic crowns for primary molars represent a promising restorative alternative, but current evidence does not demonstrate consistent superiority over stainless steel crowns. Further well-designed clinical trials with longer follow-up and standardized outcomes are needed.

Photochromic donor-acceptor molecules that produce near-infrared (NIR) absorption upon light activation offer promising platforms for organic photothermal materials. Here, neutral naphthalene diimide (NDI) derivatives with tertiary amine substituents demonstrate efficient photothermal conversion through photochromism-induced radical formation. UV irradiation initiates intermolecular electron transfer from the electron-donating amine groups to the electron-deficient NDI core, generating stable radical species with strong NIR absorption. These photoactivated states enable rapid photothermal heating under 850 nm light with efficiencies reaching up to 24.5%. When integrated into a floating evaporation platform, the optimized compound achieves a water evaporation rate of 0.98 kg m- 2 h- 1 and an energy conversion efficiency of 65.5% under 1 sun illumination. These findings highlight the potential of photochromic NDI donor-acceptor systems as adjustable organic photothermal materials for solar-driven water purification.

Hydrogels have been widely used in tissue engineering due to their high-water content and biocompatibility, yet their densely cross-linked microstructure inherently limits cell infiltration, mass transport, and mechanical support. Cryogels, formed through partial freezing and crosslinking under subzero conditions, provide unique 3D macroporous networks with excellent permeability, elasticity, and shape-memory behavior. These structural and mechanical advantages facilitate cell migration and angiogenesis, while enabling minimally invasive delivery via syringe injection and highlighting strong translational potential. In musculoskeletal tissues such as bone, cartilage, and skeletal muscle, which have distinct biomechanical requirements, cryogels allow precise control over pore size, anisotropy, hierarchical architecture, and stiffness to better emulate native functionalities. Furthermore, tunable chemical composition and surface cues enable enhanced cell-matrix interactions and biological responsiveness. In addition, recent advances that incorporate growth factors, cells, nanomaterials, and conductive or immunomodulatory elements have established cryogels as therapeutic platforms that actively contribute to regeneration. These advancements further reinforce their clinical applicability and impact. This review summarizes the principles of cryogelation, crosslinking mechanisms, and structure-property relationships and examines recent cryogel-based strategies for musculoskeletal regeneration. By comparing fabrication parameters and their regenerative outcomes, we provide engineering insights for tissue-specific scaffold design and future optimization of cryogel-based musculoskeletal repair platforms.

Lidocaine (LID) provides rapid local anesthesia but lacks nerve-type selectivity, causing undesired motor impairment, and typically suffers from a rapid washout effect. To address these acute-phase limitations, we developed biodegradable poly (lactic-co-glycolic acid) (PLGA) microparticles co-encapsulating LID and capsaicin (CAP), a transient receptor potential vanilloid 1 (TRPV1) agonist. CAP facilitates TRPV1 channel opening exclusively in sensory nerve C-fibers, allowing selective LID internalization. In vivo functional efficacy was assessed during a critical 60-min acute phase using rotarod testing and electrophysiological recordings of the saphenous nerve in the mice. While LID monotherapy caused significant motor coordination deficits and exhibited rapid dissipation of the sensory blockade within 30 min, CAP co-encapsulation successfully overcame both of these issues. Motor impairment was reduced to approximately 6-8% of that observed with lidocaine-loaded PLGA microparticles without capsaicin, preserving near-normal motor function. An electrophysiological analysis demonstrated a rapid onset of action and complete prevention of early washout, sustaining profound suppression of sensory nerve activity throughout the 60-min observation period. These findings provide compelling physiological proof-of-concept that our PLGA-based co-delivery strategy achieves rapid-onset, functionally sensory-selective, and extended acute local anesthesia. This innovative system demonstrates a strong translational potential for improving postoperative pain management and early functional recovery.

Bioengineered livers using decellularized extracellular matrix (ECM) scaffolds hold promise for transplantation therapies. However, conventional recellularization methods involving cell injection via blood vessels encounter challenges in recapitulating the complexity of hepatic tissues, including high cellularity, differentiation hierarchy, and cellular heterogeneity. Here, we developed a methodology termed "combined single-cell and organoid (CSO) injection." We injected human liver organoids (HLOs) and dispersed organoid cells via direct puncture and vascular injection into a decellularized porcine ECM scaffold, respectively. This process facilitated the construction of densely populated and self-organized liver-like tissues (CSO Livers) that formed cell-cell/cell-ECM interactions. The tissues displayed hepatic characteristics, including ALBUMIN secretion, robust expression of liver-associated genes, and cellular heterogeneity comprising hepatocytes, cholangiocytes, as well as stellate-like and endothelial cells. Furthermore, we demonstrated that CSO-Livers functioned as grafts in immunodeficient mice and in a microminipig model of liver fibrosis through transplantation via vascular anastomosis. These findings indicate the applicability of the combined single-cell and organoid (CSO) injection method for generating bioengineered liver grafts using HLOs.

Excessive fibrosis and implant-associated infections remain major challenges in wound healing and post-surgical tissue repair, often resulting in impaired regeneration and long-term complications. Although gelatin methacryloyl (GelMA) hydrogels are widely used in regenerative medicine due to their biocompatibility and tunable physicochemical properties, they intrinsically lack antifibrotic and antibacterial functionality. Herein, we report a dual-functional GelMA-based hydrogel (GelMA-AMP/AFP) achieved by the covalent co-conjugation of an antifibrotic peptide (DR8) and a broad-spectrum antimicrobial peptide (P9-4), enabling simultaneous regulation of fibrotic responses and bacterial colonization within a single biomaterial platform. The peptide-functionalized GelMA hydrogels preserved their porous microarchitecture, mechanical integrity, and swelling behavior while providing a sustained peptide release profile over 14 days. In a TGF-β1-induced in vitro fibrotic fibroblast model, the dual-functional hydrogel significantly suppressed fibroblast proliferation and migration, reduced collagen deposition, and downregulated key profibrotic markers, including COL1A1, ACTA2, FN1, and TGF-β1, at both gene and protein levels. In parallel, the same GelMA-AMP/AFP platform effectively inhibited bacterial adhesion and biofilm formation by multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA), without inducing cytotoxicity. This study reports a GelMA-based biomaterial to simultaneously integrate covalently conjugated antifibrotic and antimicrobial peptides, thereby achieving concurrent suppression of fibrosis and inhibition of biofilm formation within a single material system, in vitro. By combining complementary biological functionalities without compromising material properties, this study presents a chemically driven strategy for multifunctional biomaterial design. This strategy may provide a useful foundation for future studies targeting advanced wound dressings, post-surgical adhesion prevention, and infection-prone tissue repair, pending further in vivo validation.

Engineering implant topography has emerged as a promising strategy to promote bone regeneration in complex fractures and large bone defects. Among such topographies, TiO2 nanotubes serve as a model topography and have been shown, within a certain range, to positively regulate osteogenic differentiation through diameter-dependent effects. However, the underlying mechanisms remains fragmentary. Here, we revealed how cells perceived nanotube interfaces and identified the intracellular force-based mechanotransduction that arose from interface perception. We unexpectedly found that cellular perception of nanotube interfaces depended on diameter-associated topographical cues that induced differential distribution of adhesive ligands. Cells engaged these adhesive ligands to modulate focal adhesion (FA) organization, with small and many FAs forming on the small-diameter nanotubes (30 nm), whereas fewer but larger FAs formed on the large-diameter nanotubes (100 nm). Fewer but larger FAs regulated cytoskeletal assembly, generating greater intracellular force and enhancing cellular polarization. Furthermore, large-diameter nanotubes promoted nuclear pore deformation and YAP nuclear translocation, leading to enhanced osteogenic differentiation both in vitro and in vivo. Together, our findings suggest that nanotube diameter-dependent geometry regulates the spatial presentation of adhesive ligands and subsequently influences FA maturation, cellular polarization, and YAP-associated mechanotransduction. This study provides mechanistic insight into how implant nanotopography modulates osteogenic responses and offers a theoretical basis for the rational design of osteogenic implant surfaces.

Oral microbiomes are associated with the progression of oral squamous cell carcinoma (OSCC). Prevotella intermedia is associated with tumor progression; however, the direct effects of P. intermedia on OSCC cells have not been elucidated. In this study, the aim was to elucidate the direct effects of P. intermedia on OSCC cells. HSC-2, HSC-3, and SAS cells were treated with P. intermedia OMA14 at multiplicities of infection of 10 and 100, and cell viability was then assessed using a cell-counting kit (CCK)-8 assay. The effects of heat-killed P. intermedia OMA14 and protein fractions prepared from SDS-PAGE-separated membrane strips on HSC-3 cell viability were assessed using the CCK-8 assay. Cell migration, cell cycle, and lactate dehydrogenase (LDH) cytotoxicity assays were performed using HSC-3 cells treated with P. intermedia OMA14. Treatment with P. intermedia OMA14 reduced HSC-3 cell viability, whereas there were no significant changes in SAS or HSC-2 cell viability. Heat-killed P. intermedia did not reduce HSC-3 cell viability. P. intermedia also suppressed HSC-3 cell migration, and it induced G0/G1-phase cell-cycle arrest without increasing LDH release. In addition, among the P. intermedia-derived protein fractions, the fractions corresponding to approximately 75 kDa and 15-20 kDa had the strongest inhibitory effects on HSC-3 cell viability. P. intermedia OMA14 reduced HSC-3 cell viability through an anti-proliferative mechanism associated with G0/G1-phase cell-cycle arrest rather than overt cytotoxicity. Protein fractions of approximately 75 kDa and 15-20 kDa showed the strongest inhibitory effects on HSC-3 cell viability.

Bioadhesive materials have been successfully applied across several ophthalmic fields, yet their translation into vitreoretinal surgery for the repair of retinal breaks and defects remains limited. Conventional strategies, including gas and silicone oil tamponade, continue to dominate retinal stabilization; however, they primarily provide temporary cavity-based support rather than direct interfacial closure of retinal defects and may require postoperative positioning, secondary interventions, or carry tamponade-related complications. Despite advances in biomaterial engineering, broader translation of vitreoretinal bioadhesives remains constrained by posterior-segment-specific barriers, including inadequate wet-surface bonding, residual adherent vitreous at retinal break margins, biomechanical mismatch with the compliant neural retina, unfavorable swelling or degradation behavior, inflammatory or proliferative responses, and challenges in precise intraoperative delivery. Importantly, the required adhesive profile differs by indication: peripheral retinal breaks require focal sealing and resistance to fluid ingress and tractional stress, whereas macular holes, optic disc pit maculopathy, and regenerative retinal repair may require different balances of scaffold support, controlled bioactivity, tissue bridging, fibrosis avoidance, and long-term safety. Hydrogel-based vitreous substitutes can reproduce key viscoelastic properties of the native vitreous but remain largely investigational and primarily provide temporary intraocular support rather than direct focal defect repair. Accordingly, next-generation platforms should be designed not simply for adhesion strength, but for indication-specific function, controlled persistence, intraoperative deliverability, secondary-surgery compatibility, and rigorous preclinical and clinical validation. Rather than serving as tamponade replacements, future bioadhesives may be better conceptualized as precision intraocular platforms that complement volumetric tamponade and retinopexy by adding interface-directed defect sealing, biological modulation, and controlled intraocular delivery. This review critically reappraises vitreoretinal bioadhesive strategies, with primary emphasis on retinal detachment and defect repair, through a problem-driven, retina-centered framework that integrates clinical vitreoretinal evidence with adhesion-engineering principles, providing a barrier-oriented translational perspective for interface-directed retinal repair. Building on this analysis, we outline an innovative perspective on the key functional and translational design principles for next-generation vitreoretinal bioadhesives and propose a mechanism-informed roadmap for scalable clinical translation.