The biological inertness of Ti scaffolds prevents the proliferation and osteogenic differentiation of marrow mesenchymal stem cells (MSCs) on pure Ti scaffolds. Medical studies have shown that magnetic fields can promote the proliferation and osteogenic differentiation of stem cells, thereby promoting the production of bone tissue and fracture healing. In this work, a magnetic GelMA hydrogel coating loaded with Fe 3 O 4 magnetic nanoparticles was added onto the modified Ti surface. The introduction of GelMA hydrogel reduced the elastic modulus of the pure Ti surface and provided good environmental conditions for the proliferation and differentiation of cells. Through applying a magnetic field externally, the proliferation and osteogenic differentiation of MSCs on the composite Ti scaffolds were improved. By adjusting the direction and strength of the external magnetic field and detecting the cell viability and osteogenic differentiation index, the optimal direction and strength of the external magnetic field for the composite Ti scaffold were determined. Western Blot analysis revealed that osteogenesis was related to the JNK pathway. It was proven that the introduction of a magnetic GelMA hydrogel coating improved the proliferation and osteogenic differentiation of MSCs, and the effect of the improvement was related to the direction and strength of the external magnetic field, which provides a new strategy to bone injury repair.
Osteomyelitis (OM) is caused by the entry of septic cells into bone tissue. Due to systemic antibiotic side effects and drug resistance, local administration is a strategy for treating OM. In this study, a biodegradable, injectable thermosensitive hydrogel containing vancomycin hydrochloride (VA) was developed to reduce drug resistance and prolong the therapeutic efficacy of Staphylococcus aureus by sustained topical delivery of VA. VA was loaded into an injectable butyl glycidyl ether-modified methylcellulose hydrogel (MC-BGE), and VA-loaded MC-BGE hydrogel (VA@MC-BGE) was obtained. The gelation time of VA@MC-BGE at 37°C was approximately 10 min. In vitro, the hydrogel released ~40% of its VA payload within the first 4 days, followed by a sustained release that reached 91.0% cumulative release by Day 28. During this period, mass-loss measurements showed ~67% degradation of the hydrogel. The in vitro study showed that the VA@MC-BGE had stronger antimicrobial activity against S. aureus for at least 7 days and could reduce the cytotoxicity of VA with high osteoblast viability (> 85%) over 72 h. VA@MC-BGE inhibited S. aureus infection and improved inflammation and oxidative stress in osteoblasts. The in vivo study showed that the hydrogel was able to degrade gradually in vivo and that only a small amount of hydrogel remained at 28 days. The hydrogel was also not significantly toxic to major organs. In an OM rat model, injecting the VA@MC-BGE into the site of tibial infection in rats further reduced bone infection and improved bone regeneration compared to free VA. In conclusion, in situ thermosensitive MC-BGE hydrogels encapsulating VA have slow-release properties and good biocompatibility, which are promising for the treatment of OM.
Microfluidic technology has transformed biomedicine, environmental monitoring, and chemical analysis by enabling precise fluid control at the microliter to picoliter scale. As innovations in precision medicine, organ-on-a-chip systems, and personalized therapies accelerate, microfluidic biomaterials have become pivotal to advancing these interdisciplinary fields. These materials must possess superior mechanical strength and biocompatibility, while integrating seamlessly with microfluidic architectures to support dynamic microenvironments, high-throughput operations, and biomimetic functionalities. This review highlights recent advances in microfluidic biomaterials across three key areas: fabrication techniques (e.g., 3D printing, laser ablation, and paper-based platforms), functional enhancements (e.g., stimuli-responsive materials, surface engineering, and embedded sensors), and diverse biomedical applications (e.g., diagnostics, drug delivery, and tissue engineering). Additionally, emerging directions such as AI-assisted design, modular chip systems, and translational challenges are discussed. By addressing current gaps in standardization, reproducibility, and scale-up, this review outlines a roadmap for the future of microfluidic biomaterials in enabling next-generation healthcare, sustainable diagnostics, and intelligent biomedical devices.
The endometrium, the mucosal lining of the uterus, is a highly regenerative tissue that undergoes cyclic remodeling guided by tightly regulated levels of estrogen and progesterone. Stromal cells, including fibroblasts, are embedded within the connective tissue of the endometrium and contribute to the rapidly changing extracellular matrix (ECM). During the secretory phase, high levels of progesterone induce decidualization of endometrial fibroblasts, which changes their morphology and protein secretion. While it has been shown that the mechanical properties of endometrial tissue, such as the elastic modulus, also contribute to tissue homeostasis and pathology, the interplay between hormones and tissue modulus in contributing to ECM remodeling remains unknown. To address this, we used hydrogels of varying elastic moduli (5 and 15 kPa) to induce decidualization of endometrial fibroblasts. Using metabolic labeling of glycosylated nascent ECM proteins, we then visualized and measured the deposition of newly secreted (nascent) ECM proteins during decidualization. In addition, we designed an automated ImageJ-based workflow for unbiased quantification of nascent ECM deposition. Our results demonstrate that both 5 and 15 kPa hydrogels support decidualization of endometrial stromal fibroblasts as shown by an increase in cell flattening and prolactin secretion. While increased hydrogel modulus alone enhances nascent ECM deposition, decidualization produces an additional increase that converges to similar levels regardless of the initial hydrogel modulus. Collectively, these findings demonstrate that endometrial stromal fibroblasts deposit nascent ECM that is enhanced during decidualization. These observations may provide new insights toward future studies addressing the mechanisms of ECM remodeling in endometrial tissue.
Intervertebral disc (IVD) degeneration is a leading contributor to chronic low back pain, imposing a substantial global burden. Native IVD tissue relies on sulfated glycosaminoglycans (sGAG) to maintain hydration and mechanical function through fixed negative charges and associated osmotic pressure. With aging, sGAG depletion leads to matrix disorganization, dehydration, and pathological nerve ingrowth-hallmarks of disc degeneration. Synthetic GAG analog hydrogels have recently gained attention as biomimetic candidates for disc repair, owing to their structural resemblance and fixed charge density similarity to native sGAGs. Beyond their biomechanical role, these GAG analogs are hypothesized to act as neuroinhibitory barriers. In this study, we evaluated the neuroinhibitory capability of GAG analogs at varying crosslinking densities (0.5%-2%), using SH-SY5Y neuroblastoma cells. Grown on GAG analogs, neurite extension was markedly suppressed, with average neurite lengths < 10 μm, compared to 79.3 ± 55.8 and 157.1 ± 103.8 μm in control cultures. Importantly, cell viability remained high (75%-92%), irrespective of the presence of exogenous chondroitin sulfate (CS). These findings suggest that, beyond mimicking the mechanical properties of native NP, GAG analogs can also recapitulate the neuroinhibitory roles of native sGAG, underscoring their promise as therapeutic biomaterials for IVD regeneration and the prevention of pain-related nerve infiltration.
The in vitro expansion of mesenchymal stromal cells (MSCs) is essential to produce clinically relevant quantities of cells while preserving therapeutic potential. Currently, premature senescence of the MSCs during in vitro expansion is a significant limitation that inflates costs and reduces the efficacy of treatments. Culture environments that maintain MSC properties during in vitro expansion are urgently needed. In this study, we explored the use of the decellularized extracellular matrix (dECM) deposited from different sources of MSCs for induced pluripotent stem cell (iPSC-MSC) expansion. Specifically, we compared dECMs derived from primary bone marrow (BMSCs), a placenta-derived MSC cell line (DMSC23s), and iPSC-MSCs, against conventional substrates including tissue culture plastic (TCP), collagen type I, fibronectin, and Matrigel. We demonstrated for the first time that iPSC-MSCs deposit substantially greater amounts of dECM than BMSCs and DMSC23s (35- and 2-fold, respectively). Additionally, the dECM produced by the iPSC-MSCs demonstrated superior properties in promoting MSC proliferation and lineage-specific differentiation. Furthermore, enzyme-linked immunosorbent assays revealed that dECM culture could modulate the MSC secretome. These findings suggest that iPSC-MSCs and their ECM are suitable for optimizing and upscaling the in vitro expansion of iPSC-MSCs, offering potential advantages in regenerative therapies.
The avascular nature of tendons presents a significant challenge for postoperative healing, often resulting in complications and compromised tissue strength. This study explores a novel approach for Achilles tendon repair using a suture-based system incorporating bioactive factors. Decorin (DCN) and heparin (Hep) were selected as key biochemical factors due to their potential to modulate the tendon healing process. The optimal concentration and ratio of DCN were determined through in vitro experiments assessing their effects on tendon stem cell (TSC) proliferation and differentiation. Subsequently, Hep/DCN-loaded sutures were fabricated via electrospinning, exhibiting low immunogenicity and anti-adhesion properties. In vivo studies demonstrated enhanced collagen fibril organization and repair capacity, leading to improved tensile strength of the Achilles tendon postoperatively. These findings were confirmed through mRNA analysis and immunohistochemistry. The suture-based system established in this study not only serves as a valuable tool for investigating the molecular mechanisms underlying TSC differentiation but also holds promise as a new therapeutic strategy for clinical tendon repair applications.
Orthopedic biomaterials must both prevent infection and support bone regeneration. To achieve both outcomes with bioactive glass nanoparticles (BGNs), rational nanoarchitectural design is required to decouple and tune silver-ion (Ag+) and calcium-ion (Ca2+) release, balancing antibacterial efficacy with osteogenic compatibility. Herein, we synthesized four BGN types via a modified sol-gel route: solid spheres, Ag-doped solid spheres, core-shell mesoporous BGNs, and Ag-doped core-shell mesoporous BGNs. Core-shell architectures were generated by alkaline etching followed by calcium impregnation, and silver was introduced during synthesis. Comprehensive characterization (scanning/transmission electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy) confirmed homogeneous amorphous glass networks with spatially distinct Ca and Ag distributions in the mesoporous particles. Brunauer-Emmett-Teller analysis showed high-surface-area mesoporous BGNs (≈860 m2/g) versus solid spheres (≈17 m2/g), with markedly greater pore volume. Inductively coupled plasma mass spectrometry revealed sustained Ag+ and Ca2+ release over 21 days within sub-microgram-per-milliliter levels, consistent with the core-shell design. These physicochemical features translated into superior biological performance: Ag-doped mesoporous BGNs accelerated mineralization in simulated body fluid, exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus and Escherichia coli, and supported the viability and osteogenic differentiation of human mesenchymal stem cells. In ovo biocompatibility testing found no vascular irritation in the Hen's Egg Test on the Chorioallantoic Membrane (HET-CAM). Altogether, nanostructural tuning, particularly combining mesoporosity with a core-shell architecture, can optimize ion-release behavior and biological function in BGNs, advancing multifunctional nanoglasses for regenerative and antimicrobial applications.
Postoperative infection and aseptic loosening are leading causes of orthopedic implant failure, often necessitating complex and costly revision surgeries. Teicoplanin (TP), a glycopeptide antibiotic effective against methicillin-resistant Staphylococcus aureus (MRSA), and albumin (AB), a biocompatible carrier protein, present a promising strategy for implant surface functionalization. However, previous approaches using intermediate adhesive layers have demonstrated limited antibiotic retention following physiological conditioning. This study investigates the direct functionalization of titanium dioxide (TiO 2 ) powder with an AB-TP complex to develop a stable antibacterial surface coating capable of retaining efficacy after phosphate exposure. The AB-TP complex was prepared and immobilized onto TiO 2 powder. AB attachment kinetics and stability were assessed using the bicinchoninic acid (BCA) assay after short-term incubation, serial buffer washes, and extended conditioning. In vitro, antibacterial efficacy was evaluated against S. aureus using viable count assays and disk diffusion. Additional tests assessed TP leaching following sample conditioning. The biological response of osteoblast-like MG63 cells to AB-TP was examined to evaluate cytocompatibility and pro-osteogenic potential. AB demonstrated rapid and irreversible binding to TiO 2 , with negligible protein loss following 10 washes or 7-day physiological buffer incubation. AB-TP-TiO 2 completely inhibited bacterial growth (6.18-log reduction). Following phosphate conditioning, AB-TP-TiO 2 retained antibacterial activity, with log reductions of 3.3. Disk diffusion confirmed no TP leaching from AB-TP-TiO 2 , in contrast to TP-TiO 2 , which exhibited significant antibiotic release and complete loss of antibacterial function post-conditioning. Treatment of MG63 with the AB-TP supported significant cell growth and increased alkaline phosphatase activity. Direct functionalization of TiO 2 with the AB-TP complex yields a stable, durable, and antibacterial surface capable of withstanding physiological conditions. This approach bypasses the limitations of adhesive layers and demonstrates potential for application in orthopedic implant coatings.
Severe acute pancreatitis (SAP) is a prevalent gastrointestinal disease with no effective treatment to control inflammation currently. Macrophages, particularly peritoneal macrophages (PMOs), play a pivotal role in SAP inflammation by polarizing into M1 or M2 phenotypes, which exhibit distinct functional properties and cytokine expression profiles. Galectin-9 (Gal-9) modulates macrophage polarization, but its specific effect on PMOs in SAP remains unclear. In this study, hyaluronic acid-chitosan nanoparticles encapsulating Gal-9 (HA-CS-Gal-9 NPs) were developed for delivery. In vitro, HA-CS-Gal-9 NPs enhanced M2 marker expression and suppressed M1 markers in both naive (M0) and LPS-induced M1 macrophages. In vivo, HA-CS-Gal-9 NPs effectively delivered Gal-9, showing effective uptake by PMOs without notable toxicity, resulting in reduced IL-6, and increased IL-10 expression in PMOs. Treatment with these nanoparticles (NPs) decreased systemic pro-inflammatory cytokines, thereby alleviating pancreatitis severity. These findings demonstrate that Gal-9-loaded NPs robustly promoted M2 macrophage polarization, highlighting a promising therapeutic strategy for SAP.
The incorporation of robust meniscus-to-bone interfaces into tissue-engineered menisci is critical for their clinical translation. Generating gradients in collagen fiber organization and mineral content for tissue-engineered entheses is essential for achieving native tissue-like mechanics; however, engineering such gradients remains challenging. This study presents a tissue-engineered enthesis model consisting of a fibrochondrocyte-seeded cylinder of type I collagen gel with trabecular bone plugs on both ends. Using a tri-chamber bioreactor, spatially controlled biochemical (e.g., TGF-β1 and glucose) and biomechanical stimuli were applied, generating native-like collagen fiber structure and mechanics within tissue-engineered enthesis constructs. Confocal elastography revealed a more uniform local strain distribution and reduced peak strain in the enthesis constructs cultured in a tri-chamber bioreactor compared to those in a single chamber bioreactor, likely attributed to the enhanced collagen fiber organization. To further improve the integration at the collagen-bone plug interface, we introduced partially demineralized bone plugs to the constructs. Partial demineralization improved the mechanical performance of enthesis constructs, decreasing peak strain by > 30% and strain gradients by 50%, while increasing toughness and strain at failure by 50% and 40%, respectively. Overall, these findings highlight the importance of zone-specific biochemical and biomechanical stimuli and biomimetic scaffold materials to improve tissue-engineered implants.
Osteoporosis is an age-related bone disease closely associated with the accumulation of senescent cells in the bone marrow microenvironment, a pathological feature that is not fully addressed by current biomaterial-based therapies. Targeting cellular senescence and its associated inflammatory microenvironment presents a promising strategy for mitigating osteoporosis progression. Glycyrrhizic acid (GA), a naturally occurring triterpenoid, has been shown to alleviate cellular senescence in various age-related disorders. Herein, injectable GA/gelatin methacrylate hydrogel microspheres (GA@GelMA) were developed using microfluidic technology to enable sustained GA release. The microspheres demonstrated multiple functionalities in vitro, including suppression of cellular senescence, induction of M1-to-M2 macrophage polarization, and enhancement of osteogenic differentiation in bone marrow stem cells (BMSCs). In an ovariectomized (OVX) mouse model of osteoporosis, local administration of GA@GelMA microspheres significantly promoted bone formation and alleviated the senescence-associated inflammatory microenvironment. These GA@GelMA microspheres provide a multifunctional strategy integrating osteogenesis promotion and senescence modulation for the treatment of osteoporosis.
Skin aging is marked by fibroblast decline and extracellular matrix (ECM) degradation, prompting the widespread use of poly-L-lactic acid (PLLA) dermal injectables for activating fibroblasts, stimulating neocollagenesis, and rejuvenating the skin. However, current PLLA formulations show variable efficacy and may trigger undesirable inflammatory responses. In this study, we compared two different PLLA formulations -one containing novel microspherical PLLA (PLLA-LASYNPRO) and the other containing a microflake-like PLLA -to assess their differing effects on human dermal fibroblasts and skin tissue. The results show that PLLA microspheres promote fibroblast migration, ECM synthesis, and wound contraction, while PLLA microflakes inhibit proliferation and elicit inflammatory gene expression. Transcriptomic profiling reveals that PLLA microspheres upregulate genes involved in fat cell differentiation and energy metabolism, with minimal immune activation. In contrast, PLLA microflakes trigger immune pathways and suppress regenerative signals. Importantly, each formulation induces unique long non-coding RNA (lncRNA) signatures, implicating lncRNAs in fibroblast-mediated skin remodeling. These findings highlight the novel design of PLLA microspheres as a critical determinant of their therapeutic outcome, offering a molecular basis for developing safer and more effective skin rejuvenation strategies.
The neurovascular unit (NVU), including the blood-brain barrier (BBB), governs the interaction between neural tissue and blood vessels. The BBB is a highly selective interface that regulates molecular exchange between the bloodstream and the central nervous system. This study aimed to develop a structurally relevant, multicellular in vitro NVU model integrating both vascular and brain microenvironments to evaluate BBB function. A fibrous membrane mimicking the basement membrane was fabricated via electrospinning, while a methacrylated hyaluronic acid (MeHA)-collagen hydrogel was used on the brain side. Endothelial cells (ECs) were cultured on the vascular side, and astrocytes, pericytes, and neuronal model cells were embedded within the hydrogel. The model was optimized for cell viability and endothelial monolayer formation. Cell behavior was assessed via immunocytochemistry, and barrier function was evaluated using TEER measurements and permeability assays with fluorescein, 0.4 and 20 kDa dextran, ceftriaxone, and amikacin. CD31 expression was elevated in the multicellular model, indicating improved endothelial integrity. The model achieved a TEER of 166.86 ± 5.75 Ω versus 121.70 ± 13.58 Ω cm2 in monoculture. Permeability to tracers was significantly reduced in the multicellular model, and ceftriaxone showed higher transport than amikacin, reflecting human BBB selectivity. This model provides a physiologically relevant platform for neurovascular research and drug screening.
Collagen-like proteins (CLPs) and their congeners can form stable triple helices but show limited fibril-forming ability, restricting their application as biomaterials. To more closely replicate the structural features of natural collagen, we engineered an extended CLP-CLP double domain (CLPdd) genetically encoded with Hydroxyproline (CLPdd-Hyp) and 3,4-dihydroxyphenylalanine (CLPdd-DOPA) using a genetic code expansion strategy. This study presents the first report of the dual incorporation of Hydroxyproline (Hyp) and 3,4-dihydroxyphenylalanine (DOPA) into the CLP double domain (CLPdd), yielding the variant CLPdd-HD, which exhibited significantly enhanced fibrillation, thermal stability, and biomaterial potential. Among the engineered variants, CLPdd-Hyp showed the most pronounced improvements in triple-helical structure, fibrillation behavior, wound healing efficacy, and cell adhesion highlighting its promise as a biomaterial. Biocompatibility assessments further confirmed the suitability of CLPdd variants for biomedical applications. Notably, CLPdd-HD demonstrated exceptional thermal stability and cell-adhesive properties, underscoring its potential for further optimization. This work lays a foundation for tailoring bacterial CLPs through strategic NCAA incorporation, opening new avenues for developing advanced collagen-mimetic biomaterials.
The combination of superior mechanical properties, corrosion resistance, and biological characteristics makes Ti-6Al-4V a widely used biomaterial. However, its clinical application as an orthopedic implant is limited by its hardness and weak osseointegration capacity. This study focuses on the development of a functionally graded biomaterial that has increased bioactivity and decreased mechanical mismatch with living tissue. In this scope, a novel radially functionally graded Ti-5Mo/hydroxyapatite (HA) biocomposite was successfully fabricated via pressure-assisted sintering using a specially designed mold that enabled directional HA enrichment toward the outer surface. This architectural design addresses the persistent challenge of combining mechanical reliability with biological functionality in load-bearing implants. Comprehensive characterization was performed, including x-ray diffraction (XRD), Rietveld refinement, optical and scanning electron microscopy (SEM/EDX), atomic force microscopy (AFM), contact angle measurements, and in vitro cytotoxicity assays using L929 fibroblast cells. Mechanical behavior was assessed through Brazilian splitting, three-point bending, microhardness, and tribological testing under both dry and corrosive conditions. The biocomposite exhibited a dual-phase α + β titanium matrix and HA-derived oxides in the surface layers, with a graded increase in porosity and hardness from the core to the periphery. Mechanical tests revealed a bending modulus of 22.4 GPa, close to that of cortical bone, while the surface showed enhanced roughness, hydrophilicity (contact angle 35.3°), and corrosion resistance. In vitro results confirmed the material's biocompatibility and superior cell viability in HA-rich regions. These findings demonstrate that the developed Ti-5Mo/HA FGM offers a structurally and biologically optimized solution for orthopedic and dental implant applications.
Extensive cutaneous injuries with impaired regenerative capacity present substantial risks to both public health and socioeconomic systems. Current skin substitutes remain inadequate in fully replicating native tissue architecture and physiological functionality. While fish skin-derived gelatin-methacrylate (F-GelMA) serves as a principal scaffold material in vitro skin models, it has weak mechanical properties and limited mechanical strength, which necessitates supplementation with viscosity-enhancing additives. We created functional in vitro 3D extracellular matrix mimics with composite hydrogels based on F-GelMA and the thickener carboxymethyl cellulose (CMC). The physicochemical properties and bioactivity of the hydrogel scaffolds were assessed through testing their rheological properties, swelling behavior, degradation characteristics, and biocompatibility. It was discovered that the F-GelMA/CMC hydrogel bioscaffold loaded with adipose-derived stem cells (ADSCs) expedited wound healing by facilitating wound re-epithelialization, enhancing wound collagen formation, accelerating the deposition of myofibroblasts at the wound site, promoting angiogenesis, stimulating the proliferation and differentiation of keratinocytes, and suppressing skin wound inflammation.
Inflammatory disorders like cardiovascular diseases remain a major global health concern, with oxidative stress and chronic inflammation playing critical roles in disease progression. This study presents a PU/PCL composite functionalized with flavonoid-enriched Solanum mauritianum leaf extract (SL). Incorporation of SL into PU/PCL enhanced its hydrophilicity, oxidative stability, and anti-inflammatory properties, while enabling sustained drug release without adverse in vitro toxicity. PU/PCL/SL was fabricated using a phase inversion technique and characterized to confirm strong molecular interactions, improved thermal stability, and a porous structure that facilitated controlled release. The composite exhibited potent antioxidant and anti-inflammatory activity. PU/PCL/SL showed biocompatibility to H9c2 cardiomyocytes and Peripheral Blood Mononuclear Cells, while confocal imaging demonstrated enhanced cellular adhesion of H9c2 to PU/PCL/SL. Flow cytometry confirmed the ability of the biomaterial to reduce intracellular ROS. PU/PCL/SL was able to significantly downregulate TNF-α, IL-6, IL-1β, and TLR4 in AngII-activated cardiomyocytes. This highlighted the material's potential as an immunomodulator that can target inflammation. Collectively, these results demonstrate the successful fabrication of a flavonoid-functionalized PU/PCL composite with improved physicochemical properties, sustained release capability, and strong biological relevance through biocompatibility and immunomodulatory activity. Together, these findings position PU/PCL/SL as an advanced multifunctional biomaterial with promising applications in cardiovascular disease.
Few clinical solutions exist for cardiac fibrosis, creating the need for a tunable in vitro model to better understand fibrotic disease mechanisms and screen potential therapeutic compounds. Here, we combined cardiomyocytes, cardiac fibroblasts, and exogenous extracellular matrix (ECM) proteins to create an environmentally mediated in vitro cardiac fibrosis model. Cells and ECM were combined into 2 types of cardiac tissues-aggregates and tissue rings. The addition of collagen I had a drastic negative impact on aggregate formation, but ring formation was not as drastically affected. In both tissue types, collagen and other ECM did not severely affect contractile function. Histological analysis showed direct incorporation of collagen into tissues, indicating that we can directly modulate the cells' ECM environment. This modulation affects tissue formation and distribution of cells, indicating that this model provides a useful platform for understanding how cells respond to changes in their extracellular environment and for potential therapeutic screening.
In this study, we developed a piezoelectric-polydimethylsiloxane (pz-PDMS) composite by blending poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) with PDMS to create a biocompatible, mechanoelectrical responsive material. The pz-PDMS was synthesized with varying piezoelectric concentrations (0%, 1%, 3%, and 5%) and characterized for visual properties, mechanical properties, mechanoelectrical sensitivity, and biocompatibility. Compression testing showed no significant change in mechanical strength with the addition of piezoelectric particles, while mechanolectrical sensitivity testing revealed a non-linear increase in voltage response, with 5% pz-PDMS producing the highest sensitivity. Fatigue testing demonstrated no change in sensitivity after 7 days of cyclic displacement. Additionally, microcantilever experiments demonstrated the high fidelity of the 5% pz-PDMS to mechanical deformation. In parallel, human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes cultured on both 0% pz-PDMS and 5% pz-PDMS substrates exhibited comparable cell viability, attachment, and maturation, as confirmed by MTS assays and immunofluorescence imaging. The results suggest that 5% pz-PDMS offers a promising platform for bioelectronic applications, combining piezoelectric functionality with long-term biocompatibility.
