J Biomed Mater Res A [JOURNAL]
Sun
200 papers
ROS-Responsive Quercetin Nanoparticles Improve the Prognosis of Traumatic Brain Injury by Inhibiting Aberrant Nrf2-Keap1 Signaling Pathway Activation.
Lei Y, Dou R, Ma C … +7 more , Fang Y, Wang Z, Gao Y, Cai C, Wang X, Zhang Y, Fu X
J Biomed Mater Res A · 2026 Jul · PMID 42400341 · Publisher ↗
Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide, with secondary injury recognized as a critical therapeutic target. Quercetin (QR), a natural flavonoid, exerts antioxidant...
Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide, with secondary injury recognized as a critical therapeutic target. Quercetin (QR), a natural flavonoid, exerts antioxidant and anti-inflammatory effects by modulating the Nrf2-Keap1 pathway and shows neuroprotective potential in various neurological disorders. In this study, network pharmacology analysis identified 496 overlapping targets of QR and TBI, further highlighting the pivotal role of the Nrf2-Keap1 pathway in TBI treatment. However, the poor blood-brain barrier (BBB) permeability and low bioavailability of QR hinder effective brain-targeted delivery and limit its clinical translation. To address these challenges, we developed CAQK peptide-modified, reactive oxygen species (ROS)-responsive nanoparticles (C-PPS/Q), using PPS as the core for targeted QR delivery. C-PPS/Q exhibited ROS-triggered QR release, significantly enhanced HT22 cell uptake in vitro, reduced ROS levels and apoptosis. In a TBI mouse model, C-PPS/Q specifically accumulated at the lesion site, prolonged the half-life of QR, demonstrated excellent biocompatibility, preserved BBB integrity, attenuated neuroinflammation, inhibited aberrant Nrf2-Keap1 pathway activation, and markedly improved neurological function. Collectively, C-PPS/Q nanoparticles effectively mitigate secondary brain injury after TBI and represent a promising brain-targeted therapeutic strategy for TBI management.
Cellular Insights Into Proangiogenic Activation in Fibroblast and Endothelial Cells by Dual Drug-Loaded Emulsion Electrospun Nanofibers for Enhanced Tissue Regeneration.
Kalaiselvi V, Liya B, Karthika Y … +6 more , Praveena KD, Mol SN, Kumar AS, Ayyadurai N, Kamini NR, Ganesan P
J Biomed Mater Res A · 2026 Jul · PMID 42400334 · Publisher ↗
Emulsion electrospinning is one of the versatile methods that offer high potential encapsulation and delivery of active ingredients within the fibrous scaffolds for various applications. In this study, an efficient nanof...
Emulsion electrospinning is one of the versatile methods that offer high potential encapsulation and delivery of active ingredients within the fibrous scaffolds for various applications. In this study, an efficient nanofibrous core-shell biomaterial was fabricated for the restoration of damaged tissue using a polycaprolactone/polyvinyl alcohol-based emulsion loaded with β-carotene and keratin hydrolysate (KH) by electrospinning. The fabricated nanofiber was examined for its morphological, physicochemical, thermal, and mechanical properties. An in vitro drug release study was performed to reveal the release profiles of incorporated β-carotene and KH. The antioxidant capacity of the nanofiber was measured by DPPH and ABTS assays. The effect of nanofibers on cell morphology, proliferation, migration, adhesion, and angiogenic potential was examined using fibroblast (NIH/3 T3) and endothelial (EA.hy926) cells. The results showed that the emulsion electrospun fiber loaded with β-carotene and KH had a diameter of 249 nm, and the fibrous mat had a contact angle of 39.92°. It exhibited tensile strength of 2.05 MPa and an elongation at break value of 23.55%. A prolonged release of β-carotene and a burst release of KH from the nanofiber were noticed in the drug release study. Interestingly, nanofibers incorporated with β-carotene and KH exerted improved cell proliferation, migration, cell adhesion, and tube formation. It supported the expression of genes associated with angiogenic signaling in both fibroblast and endothelial cells. In conclusion, this study highlights the potential of electrospun nanofibers derived from emulsions for tissue regeneration, and it could be employed for accelerated wound repair when infused with β-carotene and KH.
Biomimetic Collagen Scaffolds Natural Cross-Linking Strategies via Transglutaminase and Methylglyoxal for Skin Repair.
Vaez M, Yen M, Ali A … +4 more , Huang S, Zhong L, Schuh CM, Bozec L
J Biomed Mater Res A · 2026 Jul · PMID 42396752 · Publisher ↗
Collagen-based scaffolds are widely used in tissue engineering for skin repair due to their biocompatibility and structural resemblance to extracellular matrix. However, rapid degradation and insufficient mechanical stab...
Collagen-based scaffolds are widely used in tissue engineering for skin repair due to their biocompatibility and structural resemblance to extracellular matrix. However, rapid degradation and insufficient mechanical stability limit their effectiveness. This study investigates natural cross-linking strategies utilizing Transglutaminase (TG) and Methylglyoxal (MGO) to enhance scaffold durability while maintaining biocompatibility. Monolayer and bilayer collagen scaffolds were fabricated and cross-linked using enzymatic (TG) and non-enzymatic (MGO) treatments. Cross-linking efficiency was assessed via TNBS/Hydroxyproline assays, while AFM and mechanical testing evaluated structural and mechanical properties. Cell viability (LIVE/DEAD), metabolic activity (MTS assay), and cell migration (in-growth and out-growth assays) were analyzed to assess biocompatibility and scaffold functionality. Wound healing was also assessed histologically. TG and MGO crosslinking significantly enhanced collagen fibril organization, scaffold stiffness, and enzymatic resistance. TG- and MGO-treated scaffolds exhibited a homogeneous fibrillar structure with improved mechanical integrity. Both cross-linking strategies supported high fibroblast viability and sustained metabolic activity over time. Migration assays confirmed that TG and MGO scaffolds facilitated fibroblast infiltration and wound closure. In vivo, the bilayer scaffolds with TG/MGO cross-linking showed full epithelialization, with the Tg/25 MGO group exhibiting reduced inflammation, organized collagen, and hair follicle formation, suggesting improved regeneration. These findings highlight the potential of biomimetic collagen scaffolds as wound dressings for dermal tissue regeneration and skin repair.
Granular Hydrogel Composites for Noninvasive Optical Biosensing.
Williams TJ, Saleem W, Ahn S … +3 more , Chimene D, McShane MJ, Alge DL
J Biomed Mater Res A · 2026 Jul · PMID 42390183 · Publisher ↗
Granular hydrogels are attracting increasing attention for tissue engineering and regenerative medicine applications, owing to their highly tunable physical characteristics, exceptional modularity, and naturally intercon...
Granular hydrogels are attracting increasing attention for tissue engineering and regenerative medicine applications, owing to their highly tunable physical characteristics, exceptional modularity, and naturally interconnected microporosity. These features are also attractive for next-generation biosensors that better integrate with the body. To apply the granular hydrogel paradigm to biosensor development, porphyrin-containing chemo-optical oxygen- and glucose-biosensing microdomains were encapsulated within poly(ethylene glycol) (PEG) hydrogel microparticles (80.8 ± 37.0 μm), which were fabricated using thiol-vinyl sulfone chemistry and a batch emulsification. Importantly, the granular hydrogel system demonstrated shear thinning capabilities and were annealed with a PEG-tetra-thiol linker to form granular hydrogels. This granular hydrogel platform possessed an average porosity of 25.0% ± 6.6% and a low shear storage modulus of 1448.7 ± 708.3 Pa, indicating a low crosslinking density and large mesh size, which permits analyte diffusion to the sensing microdomains. In vitro testing of granular hydrogels loaded with oxygen-biosensing microdomains demonstrated responsiveness from 0% to 21% oxygen and a Stern-Volmer quenching constant of 0.0131 ± 0.0003 μM. Additionally, in vitro testing of granular hydrogels with glucose-biosensing microdomains under a physiologically relevant oxygen concentration demonstrated a glucose sensitivity of 0.308 ± 0.068 μs·dL/mg, and a sensing range of detection from 32.8 ± 18.0 to 180.9 ± 17.8 mg/dL, which spans from hypoglycemia to mild hyperglycemia. Furthermore, biosensing performance was maintained after electron-beam sterilization. In summary, these results demonstrate proof-of-concept for integrating chemo-optical biosensors into granular hydrogels as well as the ability to measure physiologically relevant fluctuations in oxygen and glucose.
Performance Evaluation of Highly Uniform Astragalus Polysaccharide/Silk Fibroin Microspheres Fabricated via Microfluidics as Biodegradable Fillers: Collagen Regeneration and Tissue Reaction.
Yang E, Xie D, Luo Z … +2 more , Che X, Wang L
J Biomed Mater Res A · 2026 Jul · PMID 42383546 · Publisher ↗
Skin aging results from the synergistic assault of extrinsic environmental factors and intrinsic biological processes. While traditional microsphere implants promote skin rejuvenation through collagen regeneration, their...
Skin aging results from the synergistic assault of extrinsic environmental factors and intrinsic biological processes. While traditional microsphere implants promote skin rejuvenation through collagen regeneration, their clinical utility is hampered by non-biodegradability and risks such as granuloma formation. To overcome these limitations, this study employed microfluidic technology to develop highly uniform, novel injectable, highly bioactive, and degradable Astragalus polysaccharide/silk fibroin (APS/SF) composite microspheres for subcutaneous filling to promote collagen regeneration. We performed 3D simulations of droplet formation in a microfluidic chip using ANSYS Fluent to visualize the process. Experimental results indicated that these microspheres exhibited unprecedented uniformity (CV = 4.22% < 5.00%) and circularity (0.90 ± 0.01), and degraded effectively in phosphate-buffered saline solutions. Furthermore, the microspheres demonstrated excellent biocompatibility and blood compatibility. In vitro experiments confirmed their ability to significantly promote the proliferation and migration of L929 fibroblasts. In vivo animal studies further indicated that implanted microspheres effectively induced collagen regeneration. Collectively, this research highlighted the significant therapeutic potential of APS/SF microspheres as an innovative and safe biomaterial for skin rejuvenation.
Combining Supramolecular and Covalent Chemistry to Form Reinforced Fibrillar Network Hydrogels From Fibrinogen Derivatives.
Notea-Debutton N, Simaan-Yameen H, Seliktar D
J Biomed Mater Res A · 2026 Jul · PMID 42383387 · Publisher ↗
Fibrin hydrogels provide a highly supportive environment for three-dimensional cell growth and morphogenesis but are limited by insufficient stability to maintain their shape and mechanical integrity. To address this lim...
Fibrin hydrogels provide a highly supportive environment for three-dimensional cell growth and morphogenesis but are limited by insufficient stability to maintain their shape and mechanical integrity. To address this limitation, we developed a reinforced fibrin hydrogel incorporating photo-crosslinked methacrylated fibrinogen (FibMA). These interpenetrating polymer network (IPN) hydrogels were formed by thrombin-mediated activation of fibrinogen to initiate supramolecular fibrin assembly (fibrillogenesis), followed by light-activated covalent crosslinking of FibMA (photopolymerization). The unique interaction between the supramolecular and covalent chemistries, in tandem, resulted in a reinforced fibrillar network (RFN) architecture with exceptional control over mechanical properties. Precise control over the dynamic viscoelastic moduli of the FibMA-fibrin IPN hydrogel (FibMAtrx) was achieved by delaying the initiation of the photochemistry, thereby increasing the thrombin reaction time (TRT). Following covalent crosslinking, FibMAtrx exhibited more than a fivefold increase in dynamic viscoelastic moduli, depending on TRT and hydrogel composition. Fibroblasts encapsulated within FibMAtrx IPNs exhibited high viability and extensive morphogenesis, with quantitative cell spreading governed primarily by FibMA content rather than hydrogel stiffness. Cell-mediated hydrogel shrinkage after 1 week of culture (i.e., compaction) was substantially reduced in FibMAtrx IPNs, whereas fibrin single-network hydrogels compacted to a fraction of their original size. Together, these findings demonstrate the potential of proteinaceous reinforced fibrillar IPN hydrogels derived from fibrinogen and FibMA to support cell growth, enable tunable viscoelastic properties, resist compaction and enzymatic degradation, and maintain shape integrity in cell-laden fibrillar protein hydrogels.
Bioactive-Loaded Detachable Crosslinked Hyaluronic Acid Microneedles: Structural Validation and Clinical Anti-Wrinkle Efficacy.
Pukfukdee P, Ampawa S, Littirak W … +3 more , Suttiruengwong S, Asawanonda P, Wanichwecharungruang S
J Biomed Mater Res A · 2026 Jul · PMID 42383386 · Publisher ↗
Delivering a persistent biopolymer matrix to the superficial dermis remains a significant challenge for microneedle systems due to the inherent limitations of conventional dissolving platforms. Here, we present a detacha...
Delivering a persistent biopolymer matrix to the superficial dermis remains a significant challenge for microneedle systems due to the inherent limitations of conventional dissolving platforms. Here, we present a detachable microneedle design that permits rapid needle separation during administration. To biologically compensate for the relatively short 350 μm needle geometry designed for at-home safety, this system utilizes a crosslinked hyaluronic acid (cHA) matrix loaded with cosmetic peptides and functional excipients. The primary objective is to reliably deliver this composite biochemical cHA matrix into the skin to a depth of ~300 μm, which corresponds to the dermal-epidermal junction. Segmented mechanical compression analysis revealed that the non-polymeric payload did not compromise the matrix; rather, it significantly improved the initial axial stiffness from 0.059 ± 0.004 to 0.081 ± 0.005 N/mm per needle. This structural enhancement minimized axial displacement under load, enabling the 350 μm needles to reliably reach an ex vivo penetration depth of 335 ± 22 μm. A 14-day clinical evaluation (n = 28) using three-dimensional topography demonstrated excellent clinical tolerability with no adverse effects and significant reductions in surface roughness (R) and maximum wrinkle height (R) both immediately and at the conclusion of treatment.
Tunable Sol-Gel Transition in Poloxamer Blends for Injectable Osteoarticular Applications.
Tuszynska M, Skopinska-Wisniewska J, Chattahy K … +5 more , Karam A, Storey K, Ryl A, Kelly DJ, Bajek A
J Biomed Mater Res A · 2026 Jul · PMID 42383306 · Publisher ↗
Thermoresponsive poloxamers are commonly used in biomedical applications; however, their wider translational applicability depends on precisely controlling sol-gel transition behavior near body temperature while ensuring...
Thermoresponsive poloxamers are commonly used in biomedical applications; however, their wider translational applicability depends on precisely controlling sol-gel transition behavior near body temperature while ensuring injectability and a favorable biocompatibility profile. In this study, blends of three clinically relevant poloxamers were evaluated to find formulations suitable for potential injectable meniscal and joint therapies. The rheological properties and temperature-dependent gelation of these formulations were characterized, followed by testing their injectability into meniscal defects and assessing biological responses in vitro. The gelation temperatures reported in this work were operationally defined from viscosity-based temperature sweep measurements. Biocompatibility, cell viability, and migration of outer fibrochondrocytes exposed to selected poloxamer hydrogels were examined to gauge their potential for orthopedic applications. Different material behaviors emerged based on polymer composition. Synperonic F-108 combined with Poloxamer 188 showed decreased adhesiveness and aggregation, along with maintained cell viability after prolonged incubation, indicating potential as a coating material or a general structural matrix. Conversely, blends of Kolliphor K 407 with Poloxamer 188 displayed temperature-dependent increases in viscosity. They formed stable gels at body temperature, maintaining a favorable biological response in direct-contact conditions, which supports their further evaluation in long-term injectable applications with controlled structural stability. These results show that careful selection and optimization of poloxamer blends allow tailoring material properties for specific biomedical functions. The adjustable thermoresponsive behavior, chemical inertness, and simple preparation of these triblock copolymers make them practical for further development in injectable biomaterials and drug delivery systems for osteoarticular repair.
Development and Evaluation of Polyvinyl Alcohol/Carboxymethyl Chitosan Hydrocolloid Incorporating Cynodon dactylon Extract and Zinc Oxide Nanoparticle for Bedsore Healing in a Wistar Rat Model.
Molzemi S, Zamani S, Molaei M … +5 more , Mahheidari N, Naeiji M, Rezvani M, Haghi-Daredeh S, Salehi M
J Biomed Mater Res A · 2026 Jul · PMID 42364010 · Publisher ↗
Pressure ulcers present a serious clinical challenge due to their impaired healing processes and increased risk of infection, particularly for immobilized patients. This study aims to address the need for advanced wound...
Pressure ulcers present a serious clinical challenge due to their impaired healing processes and increased risk of infection, particularly for immobilized patients. This study aims to address the need for advanced wound dressings by developing a multifunctional polymeric hydrocolloid/film that blends zinc oxide (ZnO) nanoparticles, Cynodon dactylon extract, polyvinyl alcohol (PVA), and carboxymethyl chitosan (CMC). Composite hydrocolloids were fabricated via solvent casting and subsequently cross-linked with SA. We made four different formulations: pure CMC-PVA (H), CMC-PVA/ZnO (H), and CMC-PVA/C. dactylon (H), and CMC-PVA/C. dactylon/ZnO (H). The hydrocolloids were characterized using SEM, FTIR, and DLS, and their hemocompatibility, porosity, biodegradation, swelling, blood uptake, cell viability (MTT assay), potential anti-inflammatory-related effects based on protein denaturation inhibition, and in vitro release were all tested. The in vivo efficacy was assessed utilizing a Wistar rat model for pressure ulcers over a 14-day duration, incorporating histological examinations of the healed tissues. The H hydrocolloid had the best microstructure, was very porous (about 70%), broke down in a controlled way, and absorbed fluids very well. FTIR analysis confirmed that bioactive components were successfully added through hydrogen bonding and coordination interactions. The H formulation showed satisfactory hemocompatibility (< 4% hemolysis), increased fibroblast growth (112% viability at 72 h), and combined anti-inflammatory effects. The H hydrocolloid closed about 91% of the wounds in vivo, and it did a better job of epithelialization, collagen deposition, and reducing inflammation than the control groups. The CMC-PVA/C. dactylon/ZnO composite hydrocolloid demonstrates significant potential as a multifunctional wound dressing for the treatment of pressure ulcers, leveraging the synergistic effects of natural extracts and nanoparticles to promote expedited and structured tissue regeneration.
Engineering Bone-Targeted LNP Delivery of Anti-Sclerostin Antibody mRNA for the Treatment of Osteoporosis.
Ren P, Wang D, Sun W … +8 more , Li D, Yang S, Zhang S, Zhang Y, Liu Y, Hu P, Li J, Yao Q
J Biomed Mater Res A · 2026 Jul · PMID 42338194 · Publisher ↗
Messenger RNA (mRNA) therapy represents a transformative platform in regenerative medicine, but its application to skeletal disorders remains limited by the pronounced hepatic tropism of conventional lipid nanoparticle (...
Messenger RNA (mRNA) therapy represents a transformative platform in regenerative medicine, but its application to skeletal disorders remains limited by the pronounced hepatic tropism of conventional lipid nanoparticle (LNP) delivery systems. To redirect the distribution of biomolecules to bone tissue, we developed a bone-targeting mRNA nanocarrier (SA@LNP-D) through microfluidic synthesis followed by surface conjugation of the Asp8 peptide (binding to hydroxyapatite). This system enables efficient expression of anti-sclerostin antibody mRNA in bone tissue, thereby achieving therapeutic effects for osteoporosis treatment. Our in vitro experimental results have demonstrated that LNP modified with bone-targeting peptides exhibits significant bone affinity and can efficiently bind to hydroxyapatite and isolated bone. Furthermore, the in vivo results confirmed that SA@LNP-D effectively reduces hepatic sequestration and specifically accumulates in bones through mineral-directed anchoring. In a murine ovariectomy model of osteoporosis, systemic delivery of bone-targeted LNP demonstrated a stronger therapeutic effect compared to conventional LNP. It not only stimulated bone formation but also inhibited bone resorption, thereby significantly restoring trabecular bone mass and microstructure. Together, this work establishes a targeted, nonhepatic mRNA delivery strategy that offers a safe and effective therapeutic option for osteoporosis and related skeletal conditions.
Substrate Stiffness and Viscoelasticity Influence Fibroblast Senescence.
Skelton ML, Bhat T, Yu E … +2 more , Ofori A, Caliari SR
J Biomed Mater Res A · 2026 Jul · PMID 42338185 · Publisher ↗
Senescent cell accumulation has been implicated in aging and fibrotic disease, which are both characterized by increased tissue stiffness. However, the direct connection between tissue mechanics and senescence induction...
Senescent cell accumulation has been implicated in aging and fibrotic disease, which are both characterized by increased tissue stiffness. However, the direct connection between tissue mechanics and senescence induction remains disputed in the literature. Thus, this work investigates the influence of hydrogel stiffness and viscoelasticity in promoting fibroblast senescence directly and in combination with genotoxic stress. We show that while lung fibroblast YAP/TAZ signaling declines with senescence induction, senescent fibroblasts maintain their mechanosensing capabilities with increased YAP/TAZ nuclear localization on higher stiffness hydrogels. Most notably, we find a unique role for hydrogel viscoelasticity in senescence induction, with soft (2 kPa) viscoelastic substrates promoting both the onset and amplification of senescence, even in the absence of genotoxic stress. These changes are not associated with a decline in YAP/TAZ activity, but instead with a decline in nuclear DAPI intensity, suggesting a role of nuclear organization in driving this phenotype. Overall, this work highlights the influence of mechanics, and viscoelasticity in particular, on the induction of fibroblast senescence.
Biomaterial-Focused Strategies Targeting Dendritic Cells for Autoimmune Disease Treatment.
Venkata Suresh Kumar A, Babensee J
J Biomed Mater Res A · 2026 Jul · PMID 42333747 · Publisher ↗
Autoimmune diseases encompass over 100 distinct diseases where the immune cells betray our body by attacking the tissues they are meant to protect. Even though rare, 15 million Americans are collectively affected by auto...
Autoimmune diseases encompass over 100 distinct diseases where the immune cells betray our body by attacking the tissues they are meant to protect. Even though rare, 15 million Americans are collectively affected by autoimmune diseases, a number that continues to rise every year. Current treatment modalities primarily focus on alleviating symptoms rather than providing prevention or a cure. Tolerogenic dendritic cells (tolDCs) have gained popularity for autoimmune disease treatment as an alternative to traditional systemic immunosuppressive therapies due to their ability to restore immune homeostasis. However, clinical translation of tolDC therapies faces significant hurdles once injected into the body due to suboptimal delivery routes, systemic distribution throughout the body, faster clearance rate, phenotypic instability, and inefficient homing. So, the big question here is: How can we retrain dendritic cells to restore the immune balance while overcoming these challenges? Engineered biomaterials such as nanoparticles, microparticles, hydrogels, and polymer scaffolds offer innovative solutions by enabling targeted delivery of ex vivo-generated tolDCs or in situ reprogramming of endogenous dendritic cells (DCs) by delivering drugs and other bioactive agents at strategic locations. These platforms provide tunable release kinetics, enhanced targeting specificity, improved safety profiles, and high potency, highlighting their importance as a promising alternative to conventional administration methods. Biomaterials can modulate immune responses from inflammatory immune activation to immune tolerance, which is essential for long-term disease management. This review highlights recent advances in biomaterial-based delivery systems for DC delivery and their potential to redefine therapeutic strategies for autoimmune diseases.
Engineering Pro-Osteogenic Poly(l-Lactide-co-ε-caprolactone) Sponges Through Carbonate Apatite Integration.
Lou Z, Kishida R, Tsuchiya A … +1 more , Ishikawa K
J Biomed Mater Res A · 2026 Jul · PMID 42333735 · Publisher ↗
Flexible and porous sponges with high osteoconductivity have a wide range of bone healing applications. Although polymer/ceramic composite materials can serve as soft bone grafts, osteogenesis can be compromised when the...
Flexible and porous sponges with high osteoconductivity have a wide range of bone healing applications. Although polymer/ceramic composite materials can serve as soft bone grafts, osteogenesis can be compromised when the ceramic surface is covered by the polymer. This study aimed to fabricate a bone-graft sponge with high elasticity and osteoconductivity by integrating carbonate apatite (CAp) particles inside and on the surface of poly(l-lactide-co-ε-caprolactone) (PLCL). A slurry comprising PLCL and a calcium carbonate (CaCO) precursor was freeze-dried to obtain a PLCL/CaCO sponge, which was then phosphatized into a PLCL/CAp sponge using a mildly alkaline sodium phosphate solution. This sodium phosphate solution not only converted CaCO into CAp but also partially degraded the PLCL matrix to expose CAp on the surface, which improved the hydrophilicity of the surface. Interconnected macropores with diameters of 500-600 μm were also introduced by embedding and subsequently leaching sodium chloride (NaCl) crystals from the PLCL/CaCO sponge. In vitro cell experiments demonstrated that CAp and the macroporous structure significantly enhanced osteoblast adhesion and differentiation. In vivo evaluations using a rabbit femoral defect model revealed that CAp endowed the PLCL sponge with osteoconductivity, facilitating bone ingrowth from the defect margins in 4 weeks. The macroporous structure enabled bone regeneration throughout the sponge. These findings suggest that the developed PLCL/CAp sponge is a promising biomaterial for bone regenerative applications.
Evaluation of Ethyl Cellulose-Ethanol Ablation in a Human-Sized 3D Construct of High-Grade Cervical Dysplasia.
Adhikari G, Sharma A, Fogg KC … +1 more , Mueller JL
J Biomed Mater Res A · 2026 Jul · PMID 42333732 · Publisher ↗
Current preclinical models for cervical dysplasia rely on animal systems that poorly mimic human anatomy. To address this and align with emerging initiatives to reduce animal experimentation, we developed a human-sized,...
Current preclinical models for cervical dysplasia rely on animal systems that poorly mimic human anatomy. To address this and align with emerging initiatives to reduce animal experimentation, we developed a human-sized, 3D in vitro model of high-grade cervical dysplasia. The construct integrates normal human fibroblasts, keratinocytes, and SiHa cancer cells within a gelatin methacrylate (GelMA) hydrogel, engineered with a cervical "os" and asymmetric lesion to replicate native human cervical architecture. We utilized this platform to evaluate the efficacy and safety of ethyl cellulose-ethanol (EC-ethanol), a novel ablation therapy designed to mitigate the off-target leakage associated with traditional ethanol injections. While control injections of pure ethanol resulted in widespread, non-specific necrosis (approximately 99% cell death), EC-ethanol successfully formed a localized gel depot. High-resolution mapping of the ablation zone demonstrated that EC-ethanol significantly concentrated cytotoxicity within the dysplastic lesion while preserving surrounding healthy tissue. Margin analysis revealed a sharp therapeutic gradient, with cell death normalizing to background levels within approximately 2 mm of the injection site. These findings validate the translational potential of EC-ethanol as a spatially precise intervention and demonstrate the utility of macro-scale 3D models as powerful, ethical alternatives to animal testing for optimizing local drug delivery.
Mechanical Enhancement of Silk Fibroin Hydrogel Generated From Genetically-Modified Bombyx mori Cocoons and Promotes Osteogenesis.
He HX, Huang YK, Gao ZY … +7 more , Zeng HJ, Yao BH, Su DH, Tan AJ, Zhou XG, Jiang LB, Zhao MD
J Biomed Mater Res A · 2026 Jun · PMID 42295146 · Publisher ↗
Regenerated silk fibroin (RSF) from Bombyx mori is well known for its outstanding biocompatibility, biodegradability, and mechanical characteristics. Spider silk has even better strength and extensibility and is consider...
Regenerated silk fibroin (RSF) from Bombyx mori is well known for its outstanding biocompatibility, biodegradability, and mechanical characteristics. Spider silk has even better strength and extensibility and is considered one of the best silk fibers in nature. Silkworm fibroin heavy chain in fibroin and major ampullate spidroin-1 in spider silk from the spider Nephila clavipes share similar molecular weight and repetitive structure, which makes the genetic modification of silkworms possible. In our study, a novel hydrogel generated from genetically modified Bombyx mori cocoons was characterized and evaluated for potential clinical application. For the crosslinking of the hydrogel, horseradish peroxidase and HO were added to the RSF solution to create a double crosslinking structure. As a result, genetically modified regenerated silk fibroin (GMRSF) hydrogels exhibited better mechanical characteristics compared with RSF hydrogels. Additionally, compared with RSF hydrogels, GMRSF hydrogels exhibited stronger osteogenic differentiation function on rat bone mesenchymal stem cells (BMSCs). In vivo, GMRSF hydrogel also showed better osteogenic differentiation function. While the mechanism behind this remains unclear, the outstanding osteogenesis ability of GMRSF sheds light on applications in orthopaedic diseases in the future such as bone defects.
Reduced Hypotonic Exposure and Sequential Membrane Cholesterol Enrichment Limit Phosphatidylserine Externalization and Enhance Circulatory Retention of Erythrocyte-Derived Microparticles.
Zaman S, Swajian G, Iragavarapu SB … +2 more , Shoudho MTH, Anvari B
J Biomed Mater Res A · 2026 Jun · PMID 42295139 · Publisher ↗
Erythrocyte-derived carriers have emerged as effective biomimetic platforms for the delivery of therapeutic and imaging cargos. However, clearance by the mononuclear phagocytic system (MPS) limits their utility. Towards...
Erythrocyte-derived carriers have emerged as effective biomimetic platforms for the delivery of therapeutic and imaging cargos. However, clearance by the mononuclear phagocytic system (MPS) limits their utility. Towards development of standardized methods for increased bioavailability, we have developed an approach that lowers the externalization of phosphatidylserine (PS), a biomarker for MPS clearance, to the outer leaflet of the membrane. Specifically, this approach minimizes the hypotonic treatment of erythrocytes to a single cycle for depleting the hemoglobin while enriching the membrane bilayer with cholesterol during depletion, and in the subsequent cargo loading step, using indocyanine green (ICG), a fluorescent probe as an illustrative cargo. Using this strategy, PS externalization remains limited to ~16% and 9% of the carrier system with and without the encapsulated ICG, respectively, compared to ~46%-99% following multiple hypotonic cycles without cholesterol enrichment. Carriers engineered using this method exhibit significantly reduced macrophage uptake in vitro. In vivo biodistribution studies in healthy mice show ~2.7-fold increase in blood-associated fluorescence, and ~3.3-fold decrease in splenic accumulation after intravascular injection relative to carriers formed by multiple cycles of hypotonic treatment and without cholesterol enrichment. This method provides an effective approach to improve the circulatory retention of erythrocyte-based carriers.
Reciprocal Macrophage-MSC Crosstalk Drives Immunomodulatory and Regenerative Phenotypes in a Mineralized Collagen Scaffold.
Kolliopoulos V, Polanek M, Gamage HEV … +5 more , Ling MWY, Tiffany A, Nelson ER, Spiller KL, Harley BAC
J Biomed Mater Res A · 2026 Jun · PMID 42244308 · Publisher ↗
Critical sized craniomaxillofacial bone defects do not heal naturally and often exhibit chronic inflammatory responses that restrict regeneration. It is increasingly apparent that biomaterials must facilitate dynamic cro...
Critical sized craniomaxillofacial bone defects do not heal naturally and often exhibit chronic inflammatory responses that restrict regeneration. It is increasingly apparent that biomaterials must facilitate dynamic crosstalk between immune cells, such as macrophages, and osteoprogenitors to resolve inflammation and accelerate regeneration. Here, we evaluate interactions between macrophages in a neutral (M0) or pro-inflammatory (M1) state with mesenchymal stem cells (MSCs) in a basal or licensed state within a mineralized collagen scaffold. We reveal that MSC-macrophage crosstalk influences significant changes in osteoprogenitor cell differentiation and immune cell polarization. Notably, crosstalk between MSCs and macrophages drives an early-stage inflammatory response, which enhances the immunomodulatory activity of MSCs via secretion of IL-6, an effect that is heightened for already licensed MSCs. The presence of macrophages in the co-cultures upregulated osteogenic (ALPL, BMP2, COL1A2, and RUNX2) and angiogenic genes (ANGPT1) in basal MSC groups. Further, MSC-macrophage interactions subsequently drive increased M2-like macrophage polarization as early as 7 days of culture, as indicated by surface marker expression. These findings show that biomaterial scaffolds can be leveraged as mediators of MSC-mediated immunomodulation with an emphasis on achieving early-stage pro-inflammatory phenotypes that drive subsequent macrophage polarization and markers of increased regenerative potency.
Controlled Glutathione-Releasing Multifunctional Gelatin Methacryloyl/Chitosan/Zeolite Hydrogels for Accelerated Regeneration in Diabetic Wounds.
Kabadas FB, Bedir T, Ilhan E … +7 more , Kanli Z, Aydin B, Kaya E, Tinaz GB, Gursoy OM, Gunduz O, Narayan R
J Biomed Mater Res A · 2026 Jun · PMID 42237728 · Publisher ↗
Chronic diabetic wounds remain a major clinical challenge because of persistent inflammation, excessive oxidative stress, impaired angiogenesis, and high susceptibility to infection. This study aims to develop a multifun...
Chronic diabetic wounds remain a major clinical challenge because of persistent inflammation, excessive oxidative stress, impaired angiogenesis, and high susceptibility to infection. This study aims to develop a multifunctional hydrogel system composed of gelatin methacryloyl (GelMA; 7.5%, 10%, 15%), chitosan (2%), zeolite (1%), and glutathione (0.15 mg/mL) that can concurrently deliver antioxidant therapy, prevent infection, and support tissue regeneration in diabetic wounds. All GelMA/chitosan/zeolite/glutathione (Gel-CZG) hydrogels exhibited solid-like viscoelastic behavior and shear-thinning properties, with increasing GelMA concentration yielding higher stiffness. FTIR analysis confirmed the successful incorporation of glutathione, chitosan, and zeolite. SEM imaging revealed a highly interconnected porous microstructure, with pore size decreasing as GelMA concentration increased. Sustained glutathione release was achieved for up to 21 days, following a diffusion-controlled mechanism. The hydrogels were cytocompatible, supported fibroblast adhesion and proliferation, and modulated key inflammatory (e.g., IL-1β, TNF-α, IL-6, MMP13) and regenerative (e.g., IGF1, COL1A1) genes in a concentration-dependent manner. All formulations demonstrated > 90% antibacterial activity against E. coli, S. aureus, and P. aeruginosa and inhibited P. aeruginosa biofilm formation by ≥ 95%. Overall, the designed Gel-CZG hydrogels provide a robust and tunable platform that integrates sustained glutathione delivery, antibacterial action, and regenerative support.
A Multifunctional Electrospun Membrane for Full-Thickness Abdominal Wall Defect Repair.
Ma Q, Liu J, Tang R … +3 more , Zhang B, Liu Z, Wu J
J Biomed Mater Res A · 2026 Jun · PMID 42237667 · Publisher ↗
Electrospun nanofiber membranes hold promise for abdominal wall repair due to their biomimetic architecture and tunable properties. However, their porous structure often induces an elevated foreign body response (FBR) th...
Electrospun nanofiber membranes hold promise for abdominal wall repair due to their biomimetic architecture and tunable properties. However, their porous structure often induces an elevated foreign body response (FBR) that impedes tissue integration and remodeling. While previous strategies have employed ibuprofen (IBU) to mitigate inflammation, its non-selective cyclooxygenase (COX) inhibition and rapid systemic clearance limit local therapeutic efficacy. Herein, we functionalized electrospun polylactic acid (PLA)/gelatin (Gel) nanofiber-bundle membranes with chitosan (CS) and loxoprofen (LOX), a prodrug-type nonsteroidal anti-inflammatory drug with enhanced tissue penetration and cyclooxygenase-2 (COX-2) selectivity to achieve sustained local immunomodulation while preserving membrane porosity. The PLA/Gel-CS-LOX membrane exhibited favorable physicochemical properties, sustained LOX release over 28 days, and potent antibacterial activity. It showed good cytocompatibility and downregulated pro-inflammatory genes and upregulated anti-inflammatory genes of LPS-stimulated macrophages, and significantly reduced oxygen species (ROS) production. In a rat full-thickness abdominal wall defect model, the PLA/Gel-CS-LOX membrane facilitated robust cell infiltration, angiogenesis, and tissue integration. At 90 days post-implantation, regenerated tissues exhibited mechanical properties comparable to native abdominal wall, with optimized collagen remodeling evidenced by balanced matrix metalloproteinase 9 (MMP9)/tissue inhibitor of metalloproteinase 1 (TIMP1) expression. These results demonstrate that CS-LOX functionalization represents a promising strategy to modulate inflammatory responses to the electrospun mesh and promote functional tissue remodeling for clinical abdominal wall repair.
Ceragenin-Loaded Tri-Layered Skin Substitute Composed of Natural and Synthetic Biopolymers for Burn Wound Healing.
Aljayyousi N, Tamahkar Irmak E, Karaca E … +7 more , Tümay Özer E, Akgün O, Arı F, Yiğit Çınar A, Bozkurt Güzel Ç, Savage PB, Osman B
J Biomed Mater Res A · 2026 Jun · PMID 42237502 · Publisher ↗
Burn wounds present significant clinical challenges due to high infection risk, delayed healing, and extensive tissue damage. The development of biomimetic skin substitutes capable of simultaneously supporting tissue reg...
Burn wounds present significant clinical challenges due to high infection risk, delayed healing, and extensive tissue damage. The development of biomimetic skin substitutes capable of simultaneously supporting tissue regeneration and preventing infection remains a critical need in burn wound management. In this study, a novel ceragenin (CSA-44)-loaded tri-layered skin substitute was developed to mimic the epidermis, dermis, and hypodermis and address both wound healing and infection prevention simultaneously. The substitute comprised a poly(ε-caprolactone) (PCL) film as the upper layer, polyvinyl alcohol (PVA)/sodium alginate (SA)-PCL nanofibers as the middle layer, and a CSA-44-loaded PVA/Gelatin (Gel) hydrogel as the bottom layer. The tri-layered scaffold exhibited a hierarchical porous architecture, high swelling capacity (557.75% ± 52.87%), controlled degradation behavior, and a water vapor transmission rate of 2514.92 ± 63.41 g/m/day, indicating suitability for maintaining a moist wound environment. Drug release studies demonstrated controlled CSA-44 delivery, with 92.26% ± 6.90% cumulative release after 180 min. The scaffold exhibited strong antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA), with complete inhibition observed within minutes. Cytocompatibility studies using human keratinocyte (HaCaT) cells demonstrated that the ceragenin-loaded scaffold maintained acceptable cell viability within the tested concentration range. In addition, co-culture experiments with HaCaT and human umbilical vein endothelial (HUVEC) cells revealed enhanced endothelial tube formation, suggesting a favorable microenvironment for angiogenic signaling. The results suggested that the ceragenin-loaded tri-layered skin substitute holds promise as a multifunctional biomaterial for burn wound management by combining antimicrobial efficacy and tissue regeneration capability.
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