J Biomed Mater Res A [JOURNAL]
Sun
200 papers
Development and Characterization of Collagen Composites With Chemically Functionalized Mesoporous Silica Particles for Bone Tissue Engineering Applications.
Olivetti CE, Echazú MIA, Renou SJ … +5 more , Cuniglio SG, Perna O, Desimone MF, Olmedo DG, Alvarez GS
J Biomed Mater Res A · 2026 Jun · PMID 42206687 · Publisher ↗
Mesoporous silica particles (MSPs) are widely investigated in biomaterials due to their high surface area, tunable porosity, and potential for chemical functionalization. In this study, MSPs were modified with different...
Mesoporous silica particles (MSPs) are widely investigated in biomaterials due to their high surface area, tunable porosity, and potential for chemical functionalization. In this study, MSPs were modified with different anionic functional groups (carboxyl, phosphate, and sulfonate) and incorporated into Type I collagen hydrogels to evaluate their structural, biological, and drug-loading behavior in the context of bone tissue engineering. A comprehensive set of analyses including FTIR, SEM/EDS, zeta potential, porosity, drug incorporation, cytocompatibility, in vitro mineralization, and short-term in vivo response was conducted. While calcium phosphate deposition was not observed in functionalized composites, the study reveals key insights into how the surface chemistry of MSPs modulates particle-collagen interactions, drug loading efficiency, and biological responses. Phosphate-modified MSPs showed higher cytotoxicity and interfered with collagen self-assembly, whereas MSPs bearing hydroxyl or carboxyl groups maintained better cytocompatibility and distribution within the matrix. Interestingly, MSPs functionalized with sulfonate groups exhibited enhanced simvastatin loading, likely due to their reduced surface polarity resulting from the formation of siloxane bridges in the oxidation process. In vivo implantation of unloaded composites in a rat tibial defect model confirmed good biocompatibility without evidence of acute inflammation. However, no significant bone formation or biomineralization was detected after 14 days. These findings suggest that excessive negative surface charge may impair ion-mediated mineralization and that the interplay between MSP chemistry and the biological environment must be carefully balanced. This work contributes to understanding the structure-function relationships in hybrid silica-collagen systems and identifies key parameters to optimize in future designs of osteoinductive and drug-eluting scaffolds.
Pepsin Concentration Affects Structural, Physico-Chemical, Mechanical, and Biological Properties of Decellularized Extracellular Matrix Hydrogels.
Pires Figueiredo M, Copes F, Rodríguez-Fernández S … +4 more , Pouliot E, Doyen A, Létourneau-Montminy MP, Mantovani D
J Biomed Mater Res A · 2026 Jun · PMID 42206686 · Publisher ↗
Decellularized extracellular matrix (dECM) has emerged as a promising material for tissue engineering and regenerative medicine (TERM), particularly for hydrogel development. Although dECM offers unmatched biochemical co...
Decellularized extracellular matrix (dECM) has emerged as a promising material for tissue engineering and regenerative medicine (TERM), particularly for hydrogel development. Although dECM offers unmatched biochemical complexity compared to collagen type I (Coll-I), the most abundant protein in dECM and widely used in TERM, it is often reported that extraction processing-particularly pepsin digestion-compromises protein integrity and functional performance. Digestion protocols typically use 1 mg/mL pepsin and a 10:1 dECM/pepsin weight ratio, potentially leading to excessive degradation of structural proteins and diminished biological performance. This study investigated the effects of reduced pepsin concentrations (0.75 and 0.5 mg/mL) on structural, physico-chemical, mechanical, and biological features of porcine pericardium dECM hydrogels (10 mg/mL), compared to Coll-I. Compared to the standard digestion protocol, lower pepsin levels significantly improved the preservation of collagen's secondary structure and thermal stability (from 317°C ± 4°C to 324°C ± 1°C). Hydrogels digested with 0.5 mg/mL pepsin exhibited an elastic modulus of 119 ± 12 kPa, 2-3 times higher than standard dECM (65 ± 6 kPa) and Coll-I (41 ± 2 kPa), and a storage modulus of 1.5 ± 0.1 kPa, approximately twice that of the standard dECM (0.8 ± 0.1 kPa) and Coll-I (0.7 ± 0.1 kPa) hydrogels. Human dermal fibroblasts showed enhanced adhesion and over twice the viability on these optimized hydrogels. Despite dECM's intrinsic compositional advantages, its performance can be diminished by harsh digestion. Our findings highlight pepsin concentration as a critical and tunable parameter that governs the mechanical integrity and cellular responses of dECM hydrogels. Optimizing this variable enables the development of more robust, bioactive, and scalable dECM hydrogels tailored for TERM applications.
Tissue-Material Characteristics Determine Fibrous Encapsulation Dynamics Across Common Polymeric Surgical Biomaterials in a Tissue-Specific Mouse Foreign Body Response Model.
Kalashnikov N, Thareja R, Vorstenbosch J
J Biomed Mater Res A · 2026 Jun · PMID 42206683 · Publisher ↗
Common polymeric surgical biomaterials are susceptible to dysregulated fibrous encapsulation, which contributes to failure in 10% of implantable medical devices. While biomaterial factors influencing the underlying forei...
Common polymeric surgical biomaterials are susceptible to dysregulated fibrous encapsulation, which contributes to failure in 10% of implantable medical devices. While biomaterial factors influencing the underlying foreign body response have been extensively studied, the role of the implantation site-specifically the tissue microenvironment-remains poorly understood. Here, we explore the tissue-specificity of the foreign body response by evaluating fibrous encapsulation around clinically-relevant synthetic non-biodegradable polymers across distinct tissue microenvironments. We first characterize the physicochemical properties of PDMS, PP, PTFE, HDPE and nylon, and develop a mouse model that enables direct within-animal comparisons of fibrous capsule formation next to skin, bone, fat, fascia and muscle. Using this model and these biomaterials, we histologically assess the extent and quality of fibrous encapsulation at 7 and 28 days for all biomaterial-tissue combinations. At 7 days, capsules adjacent to muscle are the thickest, but-at 28 days-capsules in contact with bone and fascia reach comparable thicknesses, which are significantly greater than those of capsules adjacent to skin. Although PTFE and nylon elicit less fibrous encapsulation at 28 days than some of the other biomaterials, adjacent tissue type has a substantially greater influence on fibrous encapsulation than stiffness, roughness or wettability. Interestingly, more vascularized tissues (i.e., skin and muscle) do not show significant differences in capsule thickness over time, suggesting that they may promote a more rapid initiation and stabilization of the foreign body response. Together, these findings identify adjacent tissue type as a dominant predictor of fibrous encapsulation for common polymeric surgical biomaterials.
Evaluating the Effects of Poly(ε-Caprolactone)-Nanohydroxyapatite Composition on 3D-Printed Scaffold Structural Properties.
Kennedy MM, Kolliopoulos VK, Loukelis K … +8 more , Diaz-Gomez L, Goin AD, Sikavitsas EC, Jammalamadaka U, Jeon E, Wang FJ, Gunda V, Mikos AG
J Biomed Mater Res A · 2026 Jun · PMID 42206654 · Publisher ↗
Bone tissue engineering scaffolds should be biocompatible, match the mechanical properties of native bone, and degrade at a rate that facilitates tissue regeneration. However, most scaffolds will excel in only one or two...
Bone tissue engineering scaffolds should be biocompatible, match the mechanical properties of native bone, and degrade at a rate that facilitates tissue regeneration. However, most scaffolds will excel in only one or two of these areas while sacrificing the others. This study aims to vary poly( -caprolactone) (PCL) molecular weight blend ratios (100:0, 70:30, and 50:50 25 kDa:14 kDa PCL) and nanohydroxyapatite (nHA) ceramic content (0, 30, and 40 wt%) to design 3D-printed scaffolds with tunable mechanical properties and degradation kinetics. Nine different 3D-printing inks were created, all of which exhibited similar thermal properties. While 40 wt% nHA fibers had a homogeneous distribution of nHA, 30 wt% nHA fibers exhibited significant differences in nHA radial distribution, as characterized by micro-computed tomography. PCL with blended molecular weights had the highest compressive moduli, whereas the 0 and 30 wt% nHA groups had the highest stress at yield and peak stress before becoming brittle like the 40 wt% nHA groups. An accelerated degradation study resulted in increased PCL mass loss in the presence of nHA, suggesting nHA promoted accelerated degradation of PCL. These findings demonstrate that blending polymer molecular weights and incorporating ceramic content provides an effective means of tailoring 3D-printing inks to produce scaffolds with application-specific mechanical and degradation properties. In summary, the key novel contributions of the present work are the blending of different PCL molecular weights, the incorporation of relatively high wt% nHA, and the quantification of radial nHA distribution in individual printed fibers.
Zein Scaffold Preparation for Cultivated Meat.
Gordon EB, Nikkhah A, Madiedo-Podvrsan S … +2 more , Kaplan DL, Blackstone NT
J Biomed Mater Res A · 2026 Jun · PMID 42206649 · Publisher ↗
Cellular agriculture represents the intersection of biomaterials and cell science aimed at achieving high-quality, protein-rich, sustainable products. Developing cultivated meat products that address environmental and so...
Cellular agriculture represents the intersection of biomaterials and cell science aimed at achieving high-quality, protein-rich, sustainable products. Developing cultivated meat products that address environmental and societal challenges requires the use of natural materials that support the replication of the characteristics of traditional meats while supporting cell growth in a scalable, low environmental impact process. Here, we utilize porogen leaching to form porous zein scaffolds that provide mechanical properties (Young's Modulus of 294 ± 102 kPa) and composition (75%-80% water and 20%-25% protein and cells) mimicking commercially available meat (e.g., rump roast), while supporting the growth of immortalized bovine satellite muscle cells. Over 2 weeks, cells showed significant growth and surface coverage even after initial low attachment. Enzyme-based food softening methods were used to reduce the mechanical properties of the scaffolds to replicate the consumer post purchasing process of tenderizing meat. The process developed was analyzed by life cycle assessment (LCA). The LCA results indicated that deionized water used for leaching the porogen was the primary contributor to environmental impact (e.g., global warming and water consumption), highlighting that scaffold environmental sustainability is influenced not only by feedstock selection but also by processing decisions. The zein scaffolds demonstrated promising mechanical, chemical, and cell supportive characteristics for cellular agriculture goals. Future research should focus on zein processing and sensory analyses to ensure meat-like outcomes in the final products, as well as sustainable design of scale up processes.
Novel Antibiofilm Approach Using Bioactive Glasses F18 and 45S5 Against Clinical Isolates of Staphylococcus aureus in Chronic Rhinosinusitis.
Caetano JVB, Alves MCA, Fantucci MZ … +8 more , da Silva LECM, Garcia DM, Souza MT, Stenico RS, da Veiga MAMS, Anselmo-Lima WT, Valera FCP, Tamashiro E
J Biomed Mater Res A · 2026 May · PMID 42138481 · Publisher ↗
S. aureus plays a central role in chronic rhinosinusitis (CRS), contributing to acute exacerbations and persistent infections through biofilm formation. With rising antibiotic resistance, bioactive glasses such as F18 an...
S. aureus plays a central role in chronic rhinosinusitis (CRS), contributing to acute exacerbations and persistent infections through biofilm formation. With rising antibiotic resistance, bioactive glasses such as F18 and 45S5 have emerged as potential alternative antimicrobial agents. To evaluate the antimicrobial effects of F18 and 45S5 on S. aureus isolates from CRS patients, focusing on planktonic growth, biofilm formation, and mechanisms of action. Clinical S. aureus isolates were exposed to F18 and 45S5 (0-512 μg/mL) using a modified Calgary Biofilm Device. Biofilm biomass was quantified by crystal violet staining and spectrophotometry. A pH-controlled assay was performed to determine whether alkalinization mediated antibiofilm effects. Inductively coupled plasma analysis characterized F18 ion-release kinetics. Expression of biofilm-related genes (icaA, icaB, icaD, agrA, agrC) was quantified, and biofilm morphology was examined by scanning electron microscopy. Both bioglasses inhibited biofilm formation at concentrations ≥ 128 μg/mL but did not eradicate mature biofilms. At 512 μg/mL, F18 and 45S5 reduced the biofilm optical density by 78% and 67%, respectively. Although pH elevation occurred, biofilm inhibition was independent of pH variation. F18 exposure downregulated ica operon genes but not agr genes. Ion analysis demonstrated concentration-dependent release of Ca and Si, with no evidence of apatite formation. SEM showed reduced extracellular matrix and altered bacterial organization. F18 and 45S5 inhibit S. aureus biofilm formation through pH-independent mechanisms associated with ion release and suppression of matrix-related genes, supporting their potential as adjunctive strategies in CRS management.
Recombinant N-terminal Fragment of Human Vitronectin Promotes Osteoblast Adhesive Responses via αvβ3 and αvβ5 Integrins.
Kim OB, Jung SY, Min BM
J Biomed Mater Res A · 2026 May · PMID 42131971 · Publisher ↗
Vitronectin is a key extracellular matrix glycoprotein, but the functional contribution of specific residues within its N-terminal region to osteoblast activity remains poorly defined. We engineered a recombinant N-termi...
Vitronectin is a key extracellular matrix glycoprotein, but the functional contribution of specific residues within its N-terminal region to osteoblast activity remains poorly defined. We engineered a recombinant N-terminal fragment of human vitronectin (rVn-FI; residues 20-149) and performed a comprehensive mapping study using 16 overlapping 12-mer peptides to pinpoint the exact bioactive motifs. rVn-FI significantly promoted adhesion, spreading, and migration in HOS and MG-63 osteoblast-like cells, mediated primarily by αvβ3 and αvβ5 integrins. Peptide mapping revealed that two RGD-containing motifs-Vn-FI-P6 (AECKPQVTRGDV) and Vn-FI-P7 (PQVTRGDVFTMP)-were the sole drivers of this activity. Notably, Vn-FI-P7 exhibited a significantly higher inhibitory potency against cell adhesion to vitronectin than Vn-FI-P6, suggesting that the flanking sequences in Vn-FI-P7 provide a superior conformational context for integrin binding. None of the other 14 peptides showed biological activity, confirming the absence of non-RGD-dependent binding sites within the N-terminal fragment (residues 20-149). These results define the precise functional boundaries of the vitronectin N-terminus for osteoblast interaction. Our findings highlight that the flanking sequences in Vn-FI-P7 provide a superior conformational context for RGD-integrin binding, offering specific peptide targets for enhancing the bioactivity of bone tissue engineering scaffolds.
Biocompatibility and Therapeutic Potential of Cinnamoyl-Diphenylalanine Dipeptide: A Double-Edged Sword.
Sitsanidis ED, Ruokolainen V, Kunnas K … +5 more , Rahkola H, Sundberg LR, Vihinen-Ranta M, Pettersson M, Nissinen M
J Biomed Mater Res A · 2026 May · PMID 42102370 · Publisher ↗
This study evaluates cinnamoyl-diphenylalanine dipeptide (Cin-FF), a newly introduced gelator, for its antimicrobial efficacy, biocompatibility, and potential anticancer properties in solution and gel forms. We show that...
This study evaluates cinnamoyl-diphenylalanine dipeptide (Cin-FF), a newly introduced gelator, for its antimicrobial efficacy, biocompatibility, and potential anticancer properties in solution and gel forms. We show that Cin-FF exhibits antibacterial efficacy in the gel phase (0.2%, w/v), particularly against Escherichia coli, Acinetobacter baumannii, Staphylococcus aureus, and Bacillus subtilis, attributed to its sustained release and high concentration. In contrast, the solution phase has limited antimicrobial effects, particularly at lower concentrations (0.01% and 0.001%, w/v). The cytotoxicity of Cin-FF was evaluated across five mammalian cell lines: BJ human fibroblasts, SH-SY5Y neuroblastoma cells, mouse embryonic fibroblasts (MEF), HeLa cervical cancer cells, and Vero monkey kidney epithelial cells. Higher concentrations in the solution (0.1%, w/v) and in the gel phase (0.2%, w/v) are notably cytotoxic, particularly in the gel form. Lower concentrations in the solution form (0.01% and 0.001%, w/v) initially supported cell viability but induced delayed cytotoxicity by Day 4. Importantly, Cin-FF demonstrated potent cytotoxic effects against cancerous cell lines (HeLa and SH-SY5Y), suggesting its potential as a localized anticancer therapy. While Cin-FF in gel form shows considerable potential for both antimicrobial and anticancer applications, its cytotoxicity toward the noncancerous cells underscores the need for careful dosage control, formulation strategies, and targeted delivery to optimize therapeutic efficacy while minimizing harm to healthy tissues. This paves the way for further development as a multifunctional therapeutic agent.
Real Architecture for 3D Tissue (RAFT): Mechanical Properties and Ability to Support the 3D Culture of Porcine Corneal Endothelial Cells.
Tsai MC, Kureshi A, Daniels JT
J Biomed Mater Res A · 2026 May · PMID 42059163 · Publisher ↗
A suitable tissue-engineered equivalent is necessary to support cultured cells for cell therapy transplantation, thereby alleviating the increasing demand for donor tissue. A compressed collagen I hydrogel, Real Architec...
A suitable tissue-engineered equivalent is necessary to support cultured cells for cell therapy transplantation, thereby alleviating the increasing demand for donor tissue. A compressed collagen I hydrogel, Real Architecture For 3D Tissue (RAFT), was introduced to substitute native corneal stroma for supporting endothelial cell growth as an extracellular cellular matrix (ECM) tissue equivalent. Here, the RAFT's mechanical properties and transparency were optimized to tailor for designing a corneal endothelium transplantation graft. Meanwhile, the gene and protein expression of ZO-1, Na/K ATPase, and N-Cadherin were used to investigate the impact of mechanical properties on cell behavior. The results showed that increasing the collagen concentration and reducing the initial loading volume could generate a stiffer, thinner, and more transparent RAFT. Staining results showed that porcine corneal endothelial cells (PCECs) remained alive, forming a high cell density monolayer with ZO-1 and Na/K ATPase expressions on various stiffnesses of RAFTs. Gene and protein expression results showed that PCECs could grow on various stiffnesses of RAFTs (elastic modulus ranged from 1.17 ± 0.11 to 2.08 ± 0.14 MPa), expressing ZO-1, Na/K ATPase, and N-Cadherin. In short, RAFTs fabricated with 0.4 of 5 mg/mL collagen I shared similar optical and mechanical properties to the native cornea, with a thickness of 73.67 ± 1.70 μm, a stiffness of 0.40 ± 0.03 MPa, an elastic modulus of 1.17 ± 0.07 MPa, and light transmittance of 60.71% ± 1.17%. This is an ideal tissue-engineered cell carrier suitable for developing a cell-seeded RAFT graft for cell therapy.
A Cationic Block Co-Polymer for Gene Delivery in the Posterior Segment of the Eye.
Monteiro A, Mugisho OO, de Souza A … +6 more , Liu L, Agban Y, Agarwal P, Shome A, Rupenthal ID, Sheardown H
J Biomed Mater Res A · 2026 May · PMID 42053269 · Publisher ↗
Diseases of the back of the eye such as neovascular age-related macular degeneration (nAMD) are vision threatening and treatment is burdensome for patients, often requiring ocular injections every other month. Injection...
Diseases of the back of the eye such as neovascular age-related macular degeneration (nAMD) are vision threatening and treatment is burdensome for patients, often requiring ocular injections every other month. Injection risks and logistics lower patient compliance; however, even patients receiving optimal treatment can deteriorate. Gene silencing has shown great potential as a therapeutic alternative but is often limited by instability of the genetic payload, reducing efficacy. In the current work, a cationic block co-polymer was developed and investigated as a delivery system for an antisense oligonucleotide (ASO) to the posterior segment of the eye. This work details the synthesis, characterization, in vitro, and ex vivo testing of the polymer and the subsequent polyplexes formed between the polymer and ASO. pH-dependent polyplexes were formed which fully complexed the ASO at 1:1 and 10:1 ratios of polymer amine groups to ASO phosphate groups (N/P ratio). Neither formulation displayed a significant reduction in the viability of human retinal pigment epithelial (ARPE-19) cells. The polyplexes were under 150 nm in diameter, with a slightly negative zeta potential. In comparison to the naked ASO, the 10:1 polyplexes achieved superior transfection into ARPE-19 cells. After 24 h, the ASO delivered by the 10:1 polyplexes displayed significant knockdown of the target protein. Polyplexes were well distributed throughout the vitreous humor, retina, and choroid within 4 h of intravitreal administration in an ex vivo porcine eye. These materials show potential for gene delivery in the treatment of various posterior segment conditions including nAMD.
Reconstruction of Tissue-Engineered Conjunctiva Using Human Amniotic Epithelial Cells and Decellularized Porcine Conjunctiva Matrix With RADA16-I Peptide Hydrogel in a Perfusion Culture System.
Yuying D, Jingwen L, Fangyuan C … +5 more , Cheng L, Xiaoyong L, Yingwei W, Jian C, Qing Z
J Biomed Mater Res A · 2026 May · PMID 42053245 · Publisher ↗
Extensive conjunctival defects present significant clinical challenges due to limitations of current treatments including donor scarcity, immune rejection, and suboptimal graft outcomes. In this study, we developed a tis...
Extensive conjunctival defects present significant clinical challenges due to limitations of current treatments including donor scarcity, immune rejection, and suboptimal graft outcomes. In this study, we developed a tissue-engineered conjunctiva by integrating decellularized porcine conjunctival matrix (DPCM), human amniotic epithelial cells (hAECs), RADA16-I peptide hydrogel, and a perfusion culture system. The DPCM was prepared using a phospholipase A decellularization method and exhibited effective decellularization (93.7% DNA removal) while preserving native extracellular matrix composition. Tissue-engineered constructs were fabricated by seeding hAECs suspended in 0.5% RADA16-I peptide hydrogel onto DPCM scaffolds and cultured under perfusion conditions. Under perfusion culture, hAECs formed stratified cell layers with high viability (> 90%). Compared to static culture, perfusion significantly enhanced hAEC density, distribution uniformity, and proliferation (Ki67), while maintaining stemness marker ABCG2 expression. After 3 days, the constructs showed significant upregulation of conjunctival epithelial markers (CK4, CK13, Muc5AC) at both protein and transcriptional levels, indicating successful transdifferentiation of hAECs toward a conjunctival epithelial phenotype. This integrated approach generates a functional tissue-engineered conjunctiva that promotes hAEC proliferation, stemness maintenance, and differentiation into conjunctival epithelial cells, offering a promising alternative for ocular surface reconstruction.
Hemoglobin Nanofibrils as Electrospun Cell Scaffolds to Enhance Primary Satellite Cell Proliferation and Differentiation for Muscle Regeneration.
Chen Q, Oh JK, Feisst V … +3 more , Glasson J, Travaš-Sejdić J, Domigan LJ
J Biomed Mater Res A · 2026 May · PMID 42046475 · Publisher ↗
Stem cells are usually sensitive to extracellular matrix (ECM), and an effective synthetic ECM to mimic there in vivo growth surroundings is always desired. Poly(ɛ-caprolactone) (PCL) is a common synthetic material exten...
Stem cells are usually sensitive to extracellular matrix (ECM), and an effective synthetic ECM to mimic there in vivo growth surroundings is always desired. Poly(ɛ-caprolactone) (PCL) is a common synthetic material extensively employed for ECMs in medical regeneration applications. However, it lacks inherent bioactivity, which poses limitations to its utility. Our study provides a solution to address this drawback by incorporating hemoglobin nanofibrils (HbFs) into PCL. Leveraging the economical and easily formed HbFs, the resulting electrospun cell scaffolds exhibited improved cell adhesion of muscle satellite cells. Furthermore, these scaffolds facilitated enhanced cell proliferation, cell infiltration into the scaffold, and higher levels of expression of differentiation-related proteins. This study demonstrates the feasibility of HbFs-incorporated electrospun scaffolds as a promising ECM substitute for muscle stem cell-based regeneration therapies.
Macrophage-Targeting Biomaterials for Osteoarthritis Therapy.
Jain E, Sagoe PNK
J Biomed Mater Res A · 2026 May · PMID 42046472 · Publisher ↗
Osteoarthritis (OA) is a highly prevalent, disabling, and painful disease of the joints, characterized by progressive cartilage degeneration, synovial fibrosis, and pain. Mounting evidence highlights synovial inflammatio...
Osteoarthritis (OA) is a highly prevalent, disabling, and painful disease of the joints, characterized by progressive cartilage degeneration, synovial fibrosis, and pain. Mounting evidence highlights synovial inflammation as a key driver of OA pathogenesis, underscoring its contributive role at all disease stages. Among immune cells, macrophages, central components of the innate immune system, play a pivotal role by releasing inflammatory mediators, growth factors, and proteolytic enzymes that drive joint damage. Traditionally, drug delivery strategies sought to avoid macrophage uptake; however, recent advances have shifted toward exploiting macrophages as therapeutic targets to modulate inflammation and promote tissue repair. Targeting macrophages and abating their associated inflammatory pathways offers the potential to slow OA progression. Despite this promise, our understanding of synovial macrophage biology remains limited, and therapeutic interventions have achieved only modest success. Selectively targeting macrophage subsets or specific signaling pathways may reduce systemic side effects and enhance therapeutic precision. This review summarizes current knowledge on macrophage involvement in OA pathogenesis and highlights emerging biomaterials and nanotechnology-based strategies for macrophage targeting and reprogramming. Finally, it underscores the need for robust preclinical models and well-designed clinical trials to translate macrophage-targeted therapies into effective disease-modifying treatments for OA.
Effect of Material Properties on Neurofibromatosis Type 1 Schwann Cell Behavior.
Hampton CD, Nain S, Rain AZ … +2 more , Sakamoto T, Sundararaghavan HG
J Biomed Mater Res A · 2026 May · PMID 42023725 · Publisher ↗
Schwann cells (SC) are the principal glia in the peripheral nervous system, supporting normal peripheral nerve function, particularly in the myelination of motor and sensory axons of the peripheral nerves. In Neurofibrom...
Schwann cells (SC) are the principal glia in the peripheral nervous system, supporting normal peripheral nerve function, particularly in the myelination of motor and sensory axons of the peripheral nerves. In Neurofibromatosis Type 1 (NF1), disruptions in normal SC function can lead to decreased motor function, sensory capability, and neuropathic pain. There is no cure for NF1 and any available treatments are for symptom management such as surgical removal and drug therapies that do not always have consistent or favorable outcomes. As a result, there has been an increased interest in understanding SC behavior in NF1. This study focuses on characterizing SC response to material topography and material mechanics in an NF1 model. Based on previous studies conducted on other aberrant cells, we hypothesized that material topography, rather than mechanics alone, would have a significant impact on key behaviors such as elongation, migration, proliferation, and nerve growth factor release (NGF). We also investigated the effect of mechanics by using methacrylated hyaluronic Acid (MeHA) in this study to alter its mechanical properties through photocrosslinking (2.5-33.6 kPa). MeHA was fabricated into gels and aligned electrospun nanofibers to alter its topography. Plexiform neurofibroma Schwann cells (pNF-SCs) were cultured and cell elongation, migration, proliferation, and nerve growth factor (NGF) release were observed. Elongation was greater on nanofibers; however, migration and proliferation increased significantly on hydrogels. NGF release was the greatest on 30% substitution nanofibers. The results of this study offer further characterization of pNF-SC behavior, which can be utilized for the development of a more refined in vitro model of NF1.
Silk Scaffold Crypt-Villus Geometry Combined With L-WRN Feeder Cells Sustains Spatially Organized Epithelial Proliferation and Multilineage Differentiation.
Rudolph SE, Longo BN, Chen Y … +1 more , Kaplan DL
J Biomed Mater Res A · 2026 May · PMID 42015458 · Full text
The crypt-villus axis of the small intestine provides essential structural and biochemical cues that govern epithelial renewal, barrier function, and lineage specification. However, most existing in vitro models rely on...
The crypt-villus axis of the small intestine provides essential structural and biochemical cues that govern epithelial renewal, barrier function, and lineage specification. However, most existing in vitro models rely on flat monolayers or villus-only hydrogels, limiting their ability to capture stem cell niches and spatial organization. Here, we report silk fibroin scaffolds engineered with physiologically scaled crypt-villus topography through a combination of 3D-printed molds, vacuum-assisted silk infiltration, and water annealing. This approach reproducibly generated scaffolds with well-defined crypt and villus features and an open design that permitted visual inspection prior to seeding. When seeded with human intestinal organoid-derived monolayers, the scaffolds supported polarized epithelia with apical ZO-1, organized F-actin, and E-cadherin localization along villus axes. Differentiation protocols yielded all major intestinal lineages, including enterocytes, goblet cells, Paneth cells, and enteroendocrine cells, confirmed by immunostaining and qRT-PCR. Ultrastructural analysis further revealed dense brush-border microvilli on villi, indicative of absorptive maturation. Incorporation of L-WRN feeder cells within the scaffold bulk sustained Ki-67 positive proliferative zones and increased LGR5 transcript expression, consistent with prolonged proliferative activity. Collectively, these results establish silk-based crypt-villus scaffolds as a reproducible and versatile platform for generating spatially organized human intestinal epithelium, with potential applications in epithelial biology, host-microbe studies, and intestinal disease modeling.
In Vitro Evaluation of Periodontal Fibroblast Response to Bioinspired Porous Channel-Embedded Zirconia Surfaces.
Ribeiro J, Proença M, Rodrigues F … +6 more , Chaves D, Ferreira DP, Rimondini L, Gasik M, Silva FS, Madeira S
J Biomed Mater Res A · 2026 Apr · PMID 41982047 · Publisher ↗
Customized implant approaches are emerging to meet specific patient needs while minimizing complications. Despite advances in osseointegrated implants, issues such as excessive bone loading, bacterial infiltration, peri-...
Customized implant approaches are emerging to meet specific patient needs while minimizing complications. Despite advances in osseointegrated implants, issues such as excessive bone loading, bacterial infiltration, peri-implantitis, and bone loss persist. Bioinspired designs with customized geometries and surfaces that promote fibrointegration, inspired by the periodontal ligament of a natural tooth, are increasingly recognized as a promising strategy. This study aimed to evaluate the ability of bioinspired zirconia surfaces to promote adhesion and guide the orientation of human periodontal ligament fibroblasts (hPLFs). Zirconia specimens with internal microchannels and an external porous coating were designed to mimic dentinal tubules and cementum-like features. Fabrication was performed using CAD/CAM CNC milling, followed by dip coating with zirconia suspensions. Microstructural characterization was carried out using scanning electron microscopy (SEM). hPLFs were cultured on the surfaces under a medium gradient (2% vs. 10% FBS) to induce migration from the porous exterior toward the channeled interior. Electrical impedance spectroscopy (1-100 kHz, Gamry system) was used to complement cell viability results and to better understand fibroblast behavior, considering the combined contributions of the cell layer, the culture medium, and the electrode-electrolyte interface. Specimens with 322 ± 7.86 μm channels and porous coatings (167.04 ± 51.87 μm thickness, 9% porosity) were produced. All were biocompatible, with the highest proliferation observed on specimens combining channels and porosity. SEM analysis revealed fibroblasts embedded within the porous layer, with spindle-like extensions anchoring and extending toward channels. Channel-porous specimens also exhibited the highest impedance after 3 days, suggesting enhanced attachment, migration, and spreading. These findings indicate that channel-porous zirconia surfaces enhance fibroblast adhesion and spreading in vitro, supporting their potential to guide structured cell organization. This bioinspired design represents an initial proof of concept for improving soft tissue interactions at the implant interface, paving the way for future fibrointegrative implant concepts such as root-analogue dental implants.
Biomimetic Gelatin-Based 3D Scaffolds for Enhanced Islet Microencapsulation and Functionality in Diabetes Therapy.
Salim R, Unnikrishnan PS, Arya DA … +1 more , Thomas LV
J Biomed Mater Res A · 2026 Apr · PMID 41981993 · Publisher ↗
Tissue-engineered scaffolds are increasingly important for improving pancreatic islet transplantation, as conventional transplantation disrupts the pancreas's native vasculature and extracellular matrix, reducing islet v...
Tissue-engineered scaffolds are increasingly important for improving pancreatic islet transplantation, as conventional transplantation disrupts the pancreas's native vasculature and extracellular matrix, reducing islet viability and function. This underscores the need to develop a three-dimensional porous microencapsulation scaffold system that can replicate a supportive microenvironment, providing both mechanical stability and biological cues vital to preserving islet viability and function. This study investigated the potential of two freeze-dried and crosslinked gelatin-based scaffolds: Gelatin vinyl acetate copolymer (GeVAc) and gelatin with oxidized dextran dialdehyde (GELDEX), for supporting pancreatic islet culture. Their physicochemical properties, architecture, and wettability were analyzed using scanning electron microscopy and contact angle measurements. Both scaffolds exhibited hydrophilic, biocompatible, and structurally stable characteristics. Mouse pancreatic MIN6 cells were cultured on the scaffolds for 7 days to evaluate islet viability, extracellular matrix deposition and functionality through immunocytochemistry, glucose-stimulated insulin secretion (GSIS), and gene expression analysis. MIN6 cells adhered well to both scaffolds, forming dense monolayers and multicellular spheroids that resembled native islet clusters. GeVAc scaffolds showed significantly higher glucose sensitivity and glucose stimulation index (GSI) compared to GELDEX. While INS1 and PDX1 expression levels were comparable in both scaffolds, NKX6.1 expression was significantly higher in GeVAc. These findings indicate that scaffold architecture and surface characteristics play a crucial role in creating a supportive microenvironment for islet cluster formation, highlighting the potential of gelatin-based scaffolds as microencapsulation platforms for clinical islet transplantation in diabetes therapy.
Synthetic Mechanogenetic Gene Circuit Response in Human Induced Pluripotent Stem Cell-Derived Chondrocytes Is Altered by Matrix Stiffness.
Kim YS, Kim A, Steward N … +2 more , Strandberg K, Guilak F
J Biomed Mater Res A · 2026 Apr · PMID 41981992 · Publisher ↗
Transient receptor potential vanilloid 4 (TRPV4) is a mechanosensitive ion channel found in both excitatory and non-excitatory cells in the body. In chondrocytes, TRPV4 plays a crucial role in transducing physiologic lev...
Transient receptor potential vanilloid 4 (TRPV4) is a mechanosensitive ion channel found in both excitatory and non-excitatory cells in the body. In chondrocytes, TRPV4 plays a crucial role in transducing physiologic levels of mechanical loading and osmotic stimuli. One of the earliest tissue-level events that occur in early stages of osteoarthritis is the degradation of the cartilage extracellular and pericellular matrices. In this technical note, we highlight the development of an in vitro model system for studying the relationship between TRPV4-mediated mechanotransduction and matrix stiffness. We modeled the effects of varying degrees of degradation on cartilage mechanical properties using 3D agarose hydrogel constructs with varying concentrations, which were used to encapsulate human induced pluripotent stem cell (iPSC)-derived chondrocytes. Hydrogel stiffness significantly altered the volume of encapsulated chondrocytes, with cells in soft constructs demonstrating significantly larger volume compared to those in medium and stiff constructs. Next, we used a synthetic mechanogenetic gene circuit as a tool to investigate the stiffness-dependence of TRPV4-mediated mechanoresponsive transcription. Interestingly, chemical activation of TRPV4 (using GSK101) and hypotonic stimuli resulted in opposite trends: chondrocytes in stiffer constructs demonstrated stronger circuit response to GSK101 compared to those in softer constructs, and vice versa in response to hypotonic stimuli. These findings suggest that while increased matrix stiffness can modulate TRPV4 activity, the increased physical swelling that occurs in a softer matrix may counterbalance these effects. These results provide an initial understanding of the interplay between matrix stiffness and TRPV4-mediated mechanotransduction in chondrocytes.
Spinel-Structured MnCoO Nanoclusters Mediate Multimodal and Efficient Suppression of Drug-Resistant Bacteria.
Wu G, Wu L, Zheng Y … +3 more , Li X, Wang Y, Han Y
J Biomed Mater Res A · 2026 Apr · PMID 41968996 · Publisher ↗
The global dissemination of bacterial antibiotic resistance has emerged as a formidable public health challenge. According to the World Health Organization (WHO), drug-resistant infections claim over 1.3 million lives an...
The global dissemination of bacterial antibiotic resistance has emerged as a formidable public health challenge. According to the World Health Organization (WHO), drug-resistant infections claim over 1.3 million lives annually, with projections indicating this number could rise to 10 million by 2050. Multi-drug resistant (MDR) bacteria accelerate resistance propagation through a biofilm formation process implicated in over 80% of microbial infections coupled with efflux pump activation and genetic mutations. The biofilm's physical barrier reduces antibiotic penetration efficiency by over 90%, while sluggish therapeutic development and clinical antibiotic misuse synergistically exacerbate antimicrobial resistance. In this study, MnCoO nanoclusters (NCs) with uniform particle size, excellent dispersibility, and structural stability were synthesized via a high-temperature thermal decomposition. These NCs demonstrated exceptional biocompatibility and potent antibacterial activity. Mechanistic investigations revealed that MnCoO NCs effectively eradicate biofilms, enhance reactive oxygen species (ROS) generation, disrupt bacterial cell membranes, and induce nucleic acid leakage, ultimately leading to bacterial death. Further molecular studies elucidated that MnCoO NCs interfere with bacterial energy metabolism, cell wall synthesis, and nitrogen utilization pathways while inducing ribosomal protein translation arrest, thereby effectively suppressing the development of bacterial resistance. Collectively, MnCoO NCs represent a promising therapeutic nanomaterial for bacterial infection management.
Innovations in Implant Osseointegration: Biomaterials, Surface Engineering, and Translational Strategies.
Ahn Y, Desai PK, Rainey A … +5 more , Ayala-Ortiz JL, Ponnazhagan S, Gilbert SR, Jun HW, Cheon K
J Biomed Mater Res A · 2026 Apr · PMID 41968945 · Full text
Osseointegration is critical for the long-term success of orthopedic and dental implants. This review highlights the biological mechanisms underlying bone-implant integration and recent advances in bioactive materials, d...
Osseointegration is critical for the long-term success of orthopedic and dental implants. This review highlights the biological mechanisms underlying bone-implant integration and recent advances in bioactive materials, drug delivery systems, and surface modification strategies. Implant design features-such as geometry, porosity, and coating technologies-are discussed alongside in vitro and in vivo evaluation models. Clinical applications span orthopedics, dentistry, prosthetics, and maxillofacial reconstruction. Emerging approaches, including nitric oxide-releasing coatings and controlled BMP-2 delivery, offer promising solutions to complications such as infection and ectopic ossification. These integrated strategies aim to enhance implant stability, functionality, and long-term clinical outcomes.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe