J Biomed Mater Res A [JOURNAL]
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200 papers
Murine Biocompatibility Evaluation of an Albumin-Derived Complex and Nanoparticle Delivery System for Ocular Applications.
Abdalbaqi A, Kerur N, Ohr MP … +2 more , Palmer AF, Swindle-Reilly KE
J Biomed Mater Res A · 2026 Mar · PMID 41749475 · Full text
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the aging population, with no curative treatment currently available. Current therapies primarily target late-stage symptoms and ar...
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the aging population, with no curative treatment currently available. Current therapies primarily target late-stage symptoms and are limited by their frequent and invasive intravitreal (IVT) injections. To address oxidative stress-induced inflammation mechanisms relevant to early retinal degeneration, we developed a heme-bound human serum albumin (heme-albumin) complex designed to transiently induce heme oxygenase-1 (HO-1), a cytoprotective enzyme with antioxidant and anti-inflammatory effects. Polydopamine nanoparticles (PDA NPs) were selected as a delivery system due to their ability to scavenge reactive oxygen species (ROS) and degrade under oxidative environments. A previous in vitro study demonstrated that heme-albumin-loaded PDA NPs reduce oxidative damage and inflammatory signaling in retinal pigment epithelium (RPE) cells. This study evaluates the in vivo biocompatibility of IVT-administered heme-albumin and unloaded PDA NPs as independent components in a murine model. At the tested doses, both components showed minimal cytotoxicity with preservation of retinal structure, establishing biocompatible dosing for future evaluation in retinal disease models.
Plasma-Assisted KR-12 Conjugated PLGA Nanofibers With Dual Osteogenic and Biofilm-Inhibitory Activity.
Pulat G, Bilgiç E, Sezer B
J Biomed Mater Res A · 2026 Mar · PMID 41741969 · Publisher ↗
Multidrug-resistant bacterial infections pose a significant challenge in bone tissue engineering, primarily due to the formation of biofilms on implant surfaces, which can impede osteointegration. KR-12, a cationic antim...
Multidrug-resistant bacterial infections pose a significant challenge in bone tissue engineering, primarily due to the formation of biofilms on implant surfaces, which can impede osteointegration. KR-12, a cationic antimicrobial peptide (AMP) with dual osteoinductive and biofilm-inhibitory properties, represents a promising strategy to address this issue. Poly(lactic-co-glycolic acid) (PLGA) electrospun nanofiber (NF) scaffolds offer biocompatibility, tunable morphology, and support for cell adhesion and proliferation, making them ideal for bone regeneration. While cold atmospheric plasma (CAP) treatment has been explored to enhance peptide functionalization, covalent conjugation of KR-12 to PLGA electrospun NFs has not yet been reported. In this study, KR-12 was incorporated into electrospun PLGA NFs to create a dual-functional scaffold that promotes osteogenic differentiation while inhibiting biofilm formation. Scaffold surface properties were characterized by scanning electron microscopy (SEM) and contact angle measurements, and peptide incorporation was confirmed via fluorescein isothiocyanate (FITC) labeling and FTIR spectroscopy. Human bone marrow-derived mesenchymal stem cells cultured on KR-12-functionalized NFs exhibited enhanced alkaline phosphatase (ALP) activity, calcium and collagen deposition, and upregulated expression of collagen type I (COL1), osteopontin (OPN), and osteocalcin (OCN), as well as positive immunofluorescence staining. Antibacterial and biofilm formation inhibition activities were evaluated against multidrug-resistant MRSA and P. aeruginosa, as well as non-MDR E. coli and S. aureus, demonstrating potent inhibition of biofilm formation. KR-12-functionalized PLGA NFs thus provide a dual-functional platform for infection-resistant bone tissue regeneration, combining osteogenic support with potent inhibition of biofilm formation.
Inclusion of Chondroitin Sulfate Into a Gelatin Hydrogel Shifts Local and Global Mechanical Behavior and Fibrochondrogenic Phenotype for Applications in Insertional Tissue Engineering.
Timmer KB, Xu M, Harley BAC
J Biomed Mater Res A · 2026 Mar · PMID 41741965 · Full text
Glycosaminoglycans (GAGs) like chondroitin sulfate (CS) influence both mechanical properties and biological signals within the tissue microenvironment. CS modifications have been prevalent in a range of biomaterial desig...
Glycosaminoglycans (GAGs) like chondroitin sulfate (CS) influence both mechanical properties and biological signals within the tissue microenvironment. CS modifications have been prevalent in a range of biomaterial design strategies, particularly those with a focus on wound healing. Here, we investigate the impact of CS incorporation within a thiolated gelatin (Gel-SH) hydrogel previously established as a promising biomaterial for tendon-to-bone entheseal repair, reporting a dual biological and mechanical effect. We show that CS inclusion increases mesenchymal stem cell metabolic activity and osteo-tendinous differentiation patterns in the Gel-SH biomaterial. Additionally, we demonstrate that inclusion of CS into a Gel-SH hydrogel insertional zone used to link dissimilar tendon and bone specific collagen scaffolds induces favorable local changes in stress-strain behavior. We further show that the mode of incorporation, free incorporation of CS versus covalent tethering of oxidized CS (CSO), clearly impacts these observed effects. Overall, these results highlight promising new motifs to modulate Gel-SH hydrogels for greater promotion of enthesis-associated behavior in resident hMSCs; further, they offer broad insight into design strategies and key considerations for modification of multicompartment materials, namely in consideration of incorporation methods and on the interplay of mechanical and biological properties.
Threshold Optimization of In Situ HAPnanoclay in Polymeric Scaffolds to Enhance Biomechanical Response.
Pashaki PV, Kumari P, Ravi P … +4 more , Jaswandkar S, Noonan B, Katti KS, Katti DR
J Biomed Mater Res A · 2026 Mar · PMID 41725084 · Publisher ↗
Developing bone-mimetic tissue engineering scaffolds with tunable mechanical and biological properties is vital to overcoming obstacles in bone repair and creating realistic 3D bone models. This study utilizes montmorill...
Developing bone-mimetic tissue engineering scaffolds with tunable mechanical and biological properties is vital to overcoming obstacles in bone repair and creating realistic 3D bone models. This study utilizes montmorillonite clay (MMT) modified with amino valeric acid, featuring in situ HAP mineralization within the clay galleries, henceforth referred to as in situ HAPnanoclay. Three-dimensional scaffolds were fabricated from polymer clay nanocomposites (PCNs), where varying the amount of in situ HAPnanoclay influenced both their mechanical and biological performance. SEM and EDS analyses confirmed that the in situ HAPnanoclay was uniformly dispersed within the PCL matrix. Despite being present in small amounts, the in situ HAPnanoclay significantly enhanced the scaffolds' mechanical behavior. Incorporating as little as 1% in situ HAPnanoclay established the threshold for noticeable improvements in mechanical properties compared to pure PCL scaffolds. Cell viability studies demonstrated the scaffolds' biocompatibility, showing significantly increased cell viability when the HAPnanoclay content exceeded 3%. Additionally, the scaffolds supported osteogenic differentiation of human mesenchymal stem cells (hMSCs), with ECM mineralization improving across all HAPnanoclay loadings. Moreover, scaffolds with 5% or more in situ HAPnanoclay exhibited a substantial increase in mineralization after 23 days, identifying 5% loading as a critical threshold for enhanced biomineralization. 3D PCL/in situ HAPnanoclay scaffolds demonstrated tunable mechanical and biological properties through varying clay contents. This study is the first to report the threshold percentages of in situ HAPnanoclay modified with amino valeric acid necessary to significantly improve mechanical strength and biological performance in PCN-based scaffolds for bone regeneration.
3D Printing Polycaprolactone-Gelatin for Musculoskeletal Tissue Engineering.
Lui E, Kobayashi M, Jain C … +9 more , Maekawa H, Li J, Moeinzadeh S, Chen AAD, Allen-Hicks W, Levi B, Matsuda S, Kawai T, Yang YP
J Biomed Mater Res A · 2026 Mar · PMID 41704155 · Publisher ↗
In musculoskeletal tissue engineering, there is a need for bone implants that are biocompatible, resorbable, promote tissue regeneration, and degrade at a rate matching healing. Polycaprolactone (PCL), an FDA-approved bi...
In musculoskeletal tissue engineering, there is a need for bone implants that are biocompatible, resorbable, promote tissue regeneration, and degrade at a rate matching healing. Polycaprolactone (PCL), an FDA-approved biodegradable and bioinert polymer, can be functionalized with natural components without harsh crosslinking. This study presents the first demonstration of a homogeneous bulk polycaprolactone-gelatin (PCL-gelatin, PG) composite containing self-assembled gelatin nanoparticles that retain bioactivity despite thermal processing for 3D printing applications. PG composites with varying gelatin content (10%, 20%, and 30%) and β-tricalcium phosphate incorporation were fabricated through casting and melt processing into printable filaments at 110°C. Comprehensive characterization using mechanical testing, contact angle measurements, FTIR, TGA, EDS, and SEM confirmed homogeneous gelatin distribution as nanoscale particles throughout the PCL matrix, with systematic increases in hydrophilicity and enhanced mechanical properties proportional to gelatin content. Accelerated degradation studies revealed tunable degradation rates correlated with gelatin concentration, while in vitro studies with human mesenchymal stem cells demonstrated enhanced proliferation and early osteogenic differentiation markers, particularly in PG30 compositions. Subcutaneous implantation in rats over 24 weeks showed biocompatibility comparable to PCL with minimal inflammatory response and biphasic degradation behavior characterized by initial swelling followed by controlled volume reduction. In critical-size femoral defects, PG30 exhibited superior early mechanical properties and increased preosteoblast density at bone interfaces compared to PCL and PCL-TCP controls at 4 weeks. This developed fabrication methodology enables precise spatial control through 3D printing while preserving gelatin bioactivity. This approach offers a promising advancement for tissue engineering applications requiring enhanced cellular interactions and controlled degradation.
In Vitro Evaluation of Escherichia coli and Staphylococcus aureus Translocation in 3D Printed Material.
Sharma A, Prince J, Jones AD
J Biomed Mater Res A · 2026 Mar · PMID 41699942 · Full text
Vascular graft infection is a rare but life-threatening condition, primarily occurring after 30 days post-surgery. Meta-analysis has shown that antimicrobial coatings on graft materials do not prevent these infections. M...
Vascular graft infection is a rare but life-threatening condition, primarily occurring after 30 days post-surgery. Meta-analysis has shown that antimicrobial coatings on graft materials do not prevent these infections. Moreover, infections still occurs even though studies have shown that there is no bacterial proliferation or bacterial penetration of common vascular graft material. The time frame of infection, meta-analysis, and in situ studies suggest that bacteria present at the suture site are introduced into the surrounding tissue or that systemically circulating bacteria may be surviving, proliferating, diffusing slowly, and evading host immune defense in synthetic vascular grafts. De novo vascular graft materials, such as tissue-engineered vascular graft material and decellularized vasculature may provide an in situ platform for studying survival, proliferation, and diffusion in tissue and tissue-like materials. In this study, we used confocal microscopy to image the penetration depth of bacteria over time as a proxy for the diffusion of Staphylococcus aureus and Escherichia coli into alginate, GelMA, and decellularized porcine vascular tissue. We quantified viable bacteria breakthrough as a function of biomaterial type. We found that the penetration depth over time was similar in all three biomaterials, however E. coli broke through much less from tissue than from engineered materials, while S. aureus had higher breakthrough in the GelMa but otherwise equal rates. These results point to the possibility of interstitial growth control relative to surface coatings as a future target for engineering infection resistance in engineered vascular grafts.
Response to "Geara Et Al., Poly-L-Lactic Acid Microspheres Promote Skin Rejuvenation via Enhanced Fibroblast Function".
Avelar LE, Ma L, Widgerow A … +1 more , Bråsäter D
J Biomed Mater Res A · 2026 Feb · PMID 41691599 · Publisher ↗
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Bilayer Fiber-Reinforced Composite-Hydrogel Scaffolds With Bioactive Glass for Bone Tissue Regeneration.
Gibreel M, Ohlsbom R, Perea-Lowery L … +6 more , Lassila L, Puistola P, Hopia K, Miettinen S, Mörö A, Vallittu PK
J Biomed Mater Res A · 2026 Feb · PMID 41668613 · Publisher ↗
Bone tissue regeneration for large defects presents a significant challenge, demanding scaffolds that combine robust mechanical support alongside a bioactive environment. Hydrogels represent a promising solution for bone...
Bone tissue regeneration for large defects presents a significant challenge, demanding scaffolds that combine robust mechanical support alongside a bioactive environment. Hydrogels represent a promising solution for bone regeneration due to their biocompatibility, tunable properties, and crosslinked three-dimensional (3D) networks mimicking the natural extracellular matrix (ECM). However, their mechanical properties remain suboptimal for restoring bone defects effectively. This study introduces a novel bilayer laminate scaffold, integrating a biostable fiber-reinforced composite (FRC) with a biodegradable, 3D-printed hyaluronic acid (HA)-based hydrogel. To enhance bioactivity, bioactive glass (BAG) was incorporated into the hydrogel layer. Comprehensive characterization confirmed the scaffold's chemical and morphological properties, as well as its controlled degradation, sustained ion release, and bioactivity. Additionally, the study revealed that the BAG-induced alkaline pH shift (up to 9.24) affected hydrazone crosslinking efficiency, resulting in reduced hydrogel stiffness (86 ± 8 Pa versus 150 ± 4 Pa in control). The system showed excellent cytocompatibility, supporting high viability and proliferation of human bone marrow stem cells (BMSCs) embedded within the hydrogel component. The developed scaffolds promoted osteogenic differentiation, as evidenced by increased ALP activity and upregulated expression of osteogenic marker genes. Nevertheless, BAG incorporation did not enhance early osteogenic differentiation compared to control scaffolds. In conclusion, this bilayer scaffold offers a promising platform for bone tissue engineering (TE), providing some insights into the chemical interplay between inorganic fillers and hydrogel matrix for optimizing future scaffold designs.
Heparin-Modified Aligned Collagen Scaffolds Enhance In Vitro Myogenesis.
Bandara GC, Boudreau RD, Wyatt W … +1 more , Caliari SR
J Biomed Mater Res A · 2026 Feb · PMID 41665213 · Publisher ↗
Biomaterial-based skeletal muscle tissue engineering approaches have largely focused on mimicking the 3D aligned architecture of native muscle, which is critical for guiding myotube formation and force transmission. In c...
Biomaterial-based skeletal muscle tissue engineering approaches have largely focused on mimicking the 3D aligned architecture of native muscle, which is critical for guiding myotube formation and force transmission. In contrast, fewer studies incorporate glycosaminoglycan (GAG)-mediated biochemical cues despite their known role in regulating myogenesis and growth factor sequestration. In this study, we develop aligned collagen-GAG (CG) scaffolds using directional freeze-drying and systematically vary GAG type by incorporating GAGs of increasing sulfation levels (hyaluronic acid, chondroitin sulfate, and heparin). While all scaffold variants support myoblast adhesion, metabolic activity, and myotube alignment, heparin-modified CG scaffolds significantly enhance myoblast metabolic activity and myogenic differentiation as measured by myosin heavy chain (MHC) expression and myotube size. We additionally show that heparin-modified scaffolds sequester and retain significantly higher levels of insulin-like growth factor-1 (IGF-1), a potent promoter of myogenesis, compared to other scaffold groups. Together, these results highlight the importance of tailoring GAG type in CG scaffolds for targeted applications and underscore the promise of heparin-modified CG scaffolds as a material platform for skeletal muscle tissue engineering.
Controlled Fabrication of Alginate-Based Microspheres Incorporating Biogenic Hydroxyapatite for Enhanced Mineralization and Angiogenic Tissue Regeneration.
Thomas S, Rajendran AR, Subramanian B
J Biomed Mater Res A · 2026 Feb · PMID 41656564 · Publisher ↗
This study presents a facile and controlled approach for fabricating alginate-based microspheres integrated with biogenic hydroxyapatite (HAp) derived from bovine bone. The direct crosslinking strategy enabled the format...
This study presents a facile and controlled approach for fabricating alginate-based microspheres integrated with biogenic hydroxyapatite (HAp) derived from bovine bone. The direct crosslinking strategy enabled the formation of uniform, stable microspheres that closely replicate the composition and architecture of native bone tissue. Incorporation of biogenic HAp markedly enhanced the physicochemical stability and biological performance of the alginate matrix. The optimized microspheres demonstrated accelerated apatite nucleation within 7 days, indicating superior bioactivity and promoted the rapid sprouting of new blood vessels within 3 h, confirming their proangiogenic potential. These synergistic properties highlight the dual functionality of the developed system in supporting both osteogenic and angiogenic responses. The results further reveal that naturally sourced HAp can effectively replace synthetic analogues, providing a sustainable, cost-effective, and highly bioactive alternative for bone tissue engineering. Overall, this work establishes a simple, eco-conscious fabrication route for multifunctional biomaterials with enhanced mineralization and vascularization potential, paving the way for next-generation regenerative therapies.
Electrospun TPU Nanofibrous Membranes Incorporating Ciprofloxacin-Montmorillonite Nanoclays for Sustained Drug Release and Wound Healing.
Çalışkan T, Doymuş B, Önder S … +2 more , Kayaoğlu BK, Göcek İ
J Biomed Mater Res A · 2026 Feb · PMID 41656544 · Publisher ↗
This study aimed to develop electrospun thermoplastic polyurethane (TPU) membranes incorporating ciprofloxacin (CIP)-loaded montmorillonite (MMT) nanoclays to achieve controlled antibiotic release for wound healing appli...
This study aimed to develop electrospun thermoplastic polyurethane (TPU) membranes incorporating ciprofloxacin (CIP)-loaded montmorillonite (MMT) nanoclays to achieve controlled antibiotic release for wound healing applications. CIP was intercalated into MMT and then dispersed homogeneously within the TPU matrix to fabricate nanofibrous membranes via electrospinning. Structural and chemical analyses using X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) confirmed successful drug intercalation and interactions among CIP, MMT, and TPU. Morphological characterization by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) revealed uniform, bead-free fibers with well-dispersed additives. Drug release studies showed that CIP-loaded MMT membranes exhibited significantly slower and sustained release (12.4%-20.8% over 6 days) compared to membranes with CIP directly embedded in TPU (59.1%-73.4%), indicating effective modulation of release kinetics by MMT. Cytotoxicity tests on 3T3 fibroblasts demonstrated good biocompatibility of pure TPU membranes (> 85% viability), while MMT-containing membranes showed reduced cell viability over time, suggesting potential dose-dependent effects. Antibacterial assays confirmed that only CIP-containing membranes inhibited Staphylococcus aureus and Escherichia coli growth, with no activity observed in pure TPU or TPU/MMT controls. Overall, the results indicate that CIP-loaded MMT electrospun TPU membranes provide a promising platform for sustained drug delivery and antibacterial activity in wound dressing applications.
Hydrogel Microdroplet Based Glioblastoma Drug Screening Platform.
Payan BA, De Leon ACD, Anand T … +5 more , Thompson GB, Krishnamurthy VV, Mora-Boza A, García AJ, Harley BAC
J Biomed Mater Res A · 2026 Feb · PMID 41656536 · Full text
Glioblastoma is the most common primary malignant brain tumor with a 5-year survival rate < 5%. The standard of care involves surgical resection followed by treatment with the alkylating agent temozolomide (TMZ). GBM cel...
Glioblastoma is the most common primary malignant brain tumor with a 5-year survival rate < 5%. The standard of care involves surgical resection followed by treatment with the alkylating agent temozolomide (TMZ). GBM cells that evade surgery eventually become resistant to TMZ and lead to recurrence of tumors in patients. With only four drugs currently FDA-approved for GBM treatment, there is a need for a clinically relevant model capable of accelerating the identification of new therapies. Microgels are microscale (~10-1000 μm) hydrogel particles that can be used to encapsulate cells in a tailorable 3D matrix. Microdroplets offer short diffusion lengths relative to conventional hydrogel constructs (> 1 mm) to limit spatial distributions of hypoxia and potentially screen therapeutics in a controlled and physiologically relevant environment. Here, we establish a method to encapsulate GBM cells in gelatin and polyethylene glycol (PEG) microgels. We show that microgel composition can affect cell morphology and further, that collections of GBM-laden hydrogels can be used to quantify the effect of single versus metronomic doses of TMZ. GBM metabolic activity is maintained in microgel culture and GBM cells display drug response kinetics similar to previously established literature using macro-scale hydrogel constructs. Finally, we show microgels can be integrated with a liquid handler to enable high-throughput screening using cell-laden microgels.
Construction of a Novel Mucin/Tannic Acid Hydrogel for Diabetic Wound Repair.
Yue Y, Chen G, Cui X … +3 more , Liao Y, Liu Z, Yang D
J Biomed Mater Res A · 2026 Feb · PMID 41656534 · Publisher ↗
The excessive accumulation of reactive oxygen species (ROS) and prolonged inflammatory response in diabetic wounds impair neovascularization, resulting in chronic wounds that cause significant pain and financial burden....
The excessive accumulation of reactive oxygen species (ROS) and prolonged inflammatory response in diabetic wounds impair neovascularization, resulting in chronic wounds that cause significant pain and financial burden. To address this issue, a novel mucin/tannic acid antioxidant hydrogel (Mu-TA) was developed in a simple and eco-friendly method, leveraging the unique properties of mucin as a hydrogel substrate and the antioxidant capabilities of tannic acid. The in vitro experiments demonstrated that the hydrogel possessed excellent self-healing properties, effective ROS-scavenging capability, and high biocompatibility, significantly mitigating oxidative damage to cells. Furthermore, in the diabetic wound model established in rats, Mu-TA hydrogels downregulated pro-inflammatory factor expression, facilitated the transition of macrophages from the M1 to M2 phenotype, and enhanced neovascularization, thereby accelerating diabetic wound healing. The novel Mu-TA antioxidant hydrogel developed in this study holds significant potential for applications in regenerative medicine and tissue engineering.
Controlled Antibiotic Release From Emulsion-Loaded Alginate and Fibrin Hydrogels Using Ultrasound.
Fam ZGN, Winslow A, Fabiilli ML … +5 more , Varghese S, Oeffinger BE, Forsberg F, Hickok NJ, Delaney LJ
J Biomed Mater Res A · 2026 Feb · PMID 41656526 · Publisher ↗
Postoperative infections remain a major complication after spinal fusion surgery, often caused by biofilm-forming bacteria that resist short-term antibiotic prophylaxis. Vancomycin (VAN) is sometimes delivered locally du...
Postoperative infections remain a major complication after spinal fusion surgery, often caused by biofilm-forming bacteria that resist short-term antibiotic prophylaxis. Vancomycin (VAN) is sometimes delivered locally during surgery; however, levels diminish rapidly, leaving patients vulnerable to late-onset infections. We developed a composite hydrogel integrating perfluorohexane-based emulsions within alginate or fibrin matrices to enable both sustained and ultrasound-triggered VAN release. Water-in-oil-in-water emulsions were prepared using fluorosurfactant-stabilized perfluorohexane as the volatile oil phase, then embedded in hydrogels and exposed to ultrasound (2.5 MHz, 5.5 MPa peak negative pressure) to initiate acoustic droplet vaporization for triggered release. Drug release was quantified spectrophotometrically and with fluorescent-labeled VAN, while antibacterial efficacy was tested against Staphylococcus aureus. Hydrogels directly loaded with free VAN exhibited burst release (~55%-67% within 24 h) followed by limited sustained release, which is suboptimal for prolonged coverage. In contrast, emulsion-loaded hydrogels reduced premature leakage, retaining > 70% VAN on Day 1 and providing gradual baseline release. Ultrasound application enhanced VAN release up to 8.75-fold in alginate and 27.5-fold in fibrin hydrogels after 7 days (p < 0.0001), supporting both continuous and on-demand delivery. Only alginate-emulsion hydrogels showed measurable antibacterial activity, as drug-matrix interactions in fibrin prevented release; ultrasound-treated samples displayed significantly greater efficacy over 7 days (p < 0.05 vs. no ultrasound). This dual-mode delivery platform enables spatial and temporal control of VAN release, combining early prophylaxis with ultrasound-triggered reinforcement, and holds promise for improving infection prevention in orthopedic surgeries by aligning drug delivery with clinical timelines.
Investigation of Urinary Extracellular Vesicles as Novel and Safe Therapeutics for Autosomal Recessive Polycystic Kidney Disease (ARPKD).
Huang Y, Xing H, Osouli A … +2 more , Guay-Woodford L, Chung EJ
J Biomed Mater Res A · 2026 Feb · PMID 41656524 · Publisher ↗
Autosomal recessive polycystic kidney disease (ARPKD) is a severe inherited disorder caused primarily by mutations in PKHD1 and in a minority of cases, CYS1. These genes encode fibrocystin and cystin, respectively. ARPKD...
Autosomal recessive polycystic kidney disease (ARPKD) is a severe inherited disorder caused primarily by mutations in PKHD1 and in a minority of cases, CYS1. These genes encode fibrocystin and cystin, respectively. ARPKD typically manifests in infancy with enlarged kidneys, progressive cyst formation, and an estimated peri-natal high mortality rate of 20%. Given the lack of efficient therapies and the genetic complexity of many rare diseases such as ARPKD, strategies that restore functional proteins defective in the disease may offer a disease-modifying approach. Urinary extracellular vesicles (uEVs) are naturally secreted by renal and urinary tract cells and contain functional kidney proteins, including fibrocystin and cystin. As such, uEVs may be capable of supplementing these missing proteins and delivering them directly to diseased cells in ARPKD. To investigate the therapeutic potential of uEVs for ARPKD, we first isolated and characterized uEVs from healthy mouse urine by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting for EV markers. PCR confirmed the presence of Cys1 and Pkhd1 mRNAs in uEVs, while cellular uptake was verified by fluorescence microscopy and flow cytometry in collecting duct epithelial cells (mpkCCDc14). In vitro, uEV treatment enhanced Cys1 and Pkhd1 levels in healthy cells, and rescued Cys1 levels in Cys1-deficient cells, derived from Cys1 (cpk) mice. Upon administration in the cpk mouse model of ARPKD, uEV improved the survival rate in cpk mice. Furthermore, in utero administration of uEVs demonstrated accumulation in the fetal kidney and enhanced Cys1 level following intra-amniotic (IA) administration, highlighting the feasibility of prenatal therapy for the most severe cases of ARPKD that are lethal in utero or within the first 24-48 h after birth. Taken together, our findings reveal that uEVs represent a promising therapeutic modality for ARPKD, capable of restoring deficient CYS1 protein levels and mitigating disease progression.
Hyaluronic Acid-Based, Double Network Hydrogels With Tunable Viscoelasticity for Neural Cell Culture.
Sanazzaro T, Salazar SP, Arvinth N … +4 more , Nath A, Blottin T, Wang ZZ, Seidlits SK
J Biomed Mater Res A · 2026 Feb · PMID 41622891 · Publisher ↗
Brain tissue is the softest, most viscoelastic tissue in mammals and these mechanical properties strongly influence cell phenotypes. However, conventional hydrogels for 3D cultures rarely provide the ability to tune the...
Brain tissue is the softest, most viscoelastic tissue in mammals and these mechanical properties strongly influence cell phenotypes. However, conventional hydrogels for 3D cultures rarely provide the ability to tune the elasticity (G') independently of the viscosity (G″), making it impossible to decouple the effects of each mechanical component on cell behavior. To address this deficiency, we have developed a hyaluronic acid (HA)-based, double network hydrogel platform, in which G' and G″ can be tuned independently, keeping G' within the range observed in native brain tissue. The double network hydrogel includes a covalently photocrosslinked HA network (thiolene) to control the elasticity and a dynamically crosslinked HA (hydrazone) network to regulate the viscosity. Addition of the dynamic network to the static single networks increased viscoelasticity, as assessed by the stress-relaxation time and dissipation factor (tan(δ)), of the biomaterial fourfold over that of the covalent network alone, without affecting the storage modulus (G'). The proliferation and spreading of two neural cell types, patient-derived glioblastoma (GBM) tumor cells and mouse neural stem cells (mNSCs), were evaluated in single and double network hydrogels with varying elasticities. An increase in viscoelasticity increased cell proliferation in one patient-derived GBM line, independently of elasticity, while the converse was found in mNSCs. In both GBM and mNSCs cultures, increased cell spreading was observed in stiff double network, compared to stiff single network, gels. This double network hydrogel model allows for the orthogonal tuning of elasticity and viscosity to better represent the mechanics of CNS tissue.
Comparative Analysis of Matrigel and Tunable Collagen-Fibrin Blends for in Vitro Skeletal Muscle Models.
Mojica-Santiago JA, Agarwal G, Robles-Blasini S … +6 more , Young IC, Lopez VA, Giza S, Choi A, Malany S, Schmidt CE
J Biomed Mater Res A · 2026 Feb · PMID 41622869 · Publisher ↗
In this study, we describe the gelation kinetics, cytocompatibility, and mechanical properties of interpenetrating networks of collagen (COL), fibrin (FIB), hyaluronan (HA), and laminin (LAM) to evaluate their potential...
In this study, we describe the gelation kinetics, cytocompatibility, and mechanical properties of interpenetrating networks of collagen (COL), fibrin (FIB), hyaluronan (HA), and laminin (LAM) to evaluate their potential to produce mature skeletal muscle tissue. Skeletal muscle is a dynamic tissue that relies on the fusion of myoblasts into multinucleated myofibers to maintain homeostasis. In progressively degenerative conditions, impaired myoblast fusion leads to skeletal muscle atrophy and significant mass loss. Three-dimensional (3D) in vitro models for skeletal muscle disease have been developed to better understand disease mechanisms and facilitate drug screening. However, most rely on Matrigel, a tumor-derived matrix that supports robust cell growth but has limited clinical relevance. To address this limitation, we focused on creating natural, multi-component scaffolds specifically tailored for muscle applications with clinically relevant drug testing use. Using spectrophotometry and rheology, we characterized the gelation kinetics and viscoelastic properties of interpenetrating networks with varying mass ratios of COL to FIB, supplemented with fixed proportions of HA and LAM. Tunable gelation was achieved within a range of 10 to 16 min. Cytocompatibility studies with C2C12 murine myoblasts demonstrated favorable cell viability in 1:1 and 1:2 (w/w) COL:FIB blends incorporating HA and LAM. Immunostaining of differentiated C2C12 cells confirmed Myosin 4 Monoclonal Antibody (MF-20) expression in these blends when seeded into polydimethylsiloxane (PDMS)-anchored bundles. Notably, in cell-laden 1:1 COL:FIB gels with a seeding density of 10 × 10 cells/mL, the compressive modulus increased three-fold between days 4 and 7 of differentiation. These findings highlight the potential of COL:FIB interpenetrating networks, enhanced with HA and LAM, as promising scaffolds for developing clinically relevant models of skeletal muscle tissue.
A Photoinitiator-Free Bioink Platform: Tyrosine-Assisted UV Crosslinking of Decellularized Extracellular Matrix/Zein Scaffolds Optimized by Full Factorial Design.
Coşkun B, Biçen Ünlüer Ö
J Biomed Mater Res A · 2026 Feb · PMID 41603126 · Publisher ↗
The clinical translation of 3D-bioprinted tissues is significantly limited by the cytotoxicity of synthetic photoinitiators used in photopolymerizable bioinks. To address this critical challenge, we developed a novel, fu...
The clinical translation of 3D-bioprinted tissues is significantly limited by the cytotoxicity of synthetic photoinitiators used in photopolymerizable bioinks. To address this critical challenge, we developed a novel, fully photoinitiator-free bioink platform based on methacrylated decellularized extracellular matrix (dECM-MA) and a biomacromolecular crosslinker zein (BMC-Z). The key innovation of this work is the exploitation of the innate UV reactivity of tyrosine residues naturally abundant in dECM, which function as an intrinsic photoinitiator system. BMC-Z plays a dual role, simultaneously providing immediate rheological stability through a hydrophobic physical network and enhancing the tyrosine-mediated radical generation for covalent photocrosslinking. A Full Factorial Design (FFD) was employed to efficiently optimize the complex interactions between dECM-MA, hyaluronic acid (HA), hydroxyapatite (HAp), and BMC-Z. The optimal formulation (40 mg/mL dECM-MA, 2 mg/mL HA, 3 mg/mL HAp, 160 μL BMC-Z) exhibited excellent viscoelastic properties (tan δ = 0.286) and significantly enhanced storage modulus (G'). Remarkably, this bioink supported outstanding biological performance, demonstrating 95% ± 3% cell viability over 14 days and a 4.8-fold increase in cell proliferation (4.16 × 10 → 2.0 × 10 cells/scaffold). This study introduces a paradigm-shifting, non-toxic, and high-performance bioink strategy that effectively eliminates the dependency on exogenous photoinitiators, paving the way for safer and more clinically relevant tissue engineering applications.
Injectable Butyl Glycidyl Ether-Modified Methylcellulose Thermosensitive Hydrogel for Topical Delivery of Vancomycin Hydrochloride in the Treatment of Osteomyelitis.
Zhi C, Wang G, Zhou B … +3 more , Liu P, Kang Y, Chen W
J Biomed Mater Res A · 2026 Feb · PMID 41586469 · Publisher ↗
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,...
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.
Fabrication of Titanium-Based Magnetic Composite Scaffold In Vitro Evaluation of Osteogenic Performance.
Zhang J, Xia Z, Xu Z … +4 more , Zhang H, Zhao H, Li Q, Cai K
J Biomed Mater Res A · 2026 Feb · PMID 41586456 · Publisher ↗
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 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 FeO 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.
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