J Biomed Mater Res A [JOURNAL]
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200 papers
Submucosal Hydrogel for Spring-Mediated Intestinal Lengthening.
Salimi-Jazi F, de Paiva Narciso N, Fell G … +9 more , Thomas AL, Navarro RS, Rafeeqi T, Baugh NJ, Suhar RA, Nguyen JA, Lopez N, Heilshorn SC, Dunn JCY
J Biomed Mater Res A · 2025 Oct · PMID 40977628 · Publisher ↗
Spring-mediated distraction enterogenesis has shown success in intestinal lengthening, with spring confinement achieved by external plication with sutures to reduce the lumen diameter at both ends of the intestinal segme...
Spring-mediated distraction enterogenesis has shown success in intestinal lengthening, with spring confinement achieved by external plication with sutures to reduce the lumen diameter at both ends of the intestinal segment. Endoscopic spring placement would minimize the morbidity associated with device insertion. This study investigates the use of submucosal injection of engineered hydrogel to temporarily confine a compressed spring within an intestinal segment. Engineered hydrogels were composed of hyaluronic acid (HA) alone or HA with elastin-like protein (HELP). To simulate endoscopic injection in six juvenile pigs, hydrogel was injected into the submucosa in everted jejunum, followed by the placement of a gelatin-encapsulated, compressed nitinol spring. The jejunum was then unfolded over the spring, and hydrogel was injected distally into the submucosa. Sutures were placed as fiducial markers. After 7 days on a liquid diet, the pigs were euthanized, and their intestinal segments were analyzed for lengthening and histological changes. The spring-containing jejunal segments expanded in all animals, lengthening to 132% in the HA group and 188% in the HELP group. HELP hydrogels exhibited slower biodegradation than HA-only hydrogels. Histological analysis showed increased crypt width and decreased crypt density in the spring-containing segments compared to controls. Hydrogel effectively provides temporary spring confinement within intestinal segments without adverse effects. The mechanical stimulation from the spring induces crypt fission, expanding the intestinal epithelium. These results support the feasibility of gel-enabled, spring-mediated distraction enterogenesis for intestinal lengthening.
Mechanochromic Polyurethane Shape Memory Polymer for Biomedical Applications.
Orado T, Yashkus B, Chandardat R … +6 more , Zysk S, Geffert ZJ, Obeng EE, Lu X, Soman P, Monroe MBB
J Biomed Mater Res A · 2025 Oct · PMID 40977599 · Publisher ↗
The incorporation of functional molecular switches into smart materials imparts dynamic material properties, gaining deeper insight into how molecular structure affects the functionality of these materials and aiding the...
The incorporation of functional molecular switches into smart materials imparts dynamic material properties, gaining deeper insight into how molecular structure affects the functionality of these materials and aiding the development of novel sensor devices. To enable mechanochromic biomaterials capable of sensing shape changes, we explored the incorporation of spiropyran (SP) mechanophores into a polyurethane (PUR) shape memory polymer (SMP). SPs reversibly generate variations in fluorescence and visual colors due to conversion from inactivated SP to activated merocyanine (MC) in response to force. We hypothesized that SP-containing PUR (PUR-SP) could undergo simultaneous shape and color changes. Small quantities of SP were dissolved in control PUR solutions with different hard-to-soft segment ratios, and PUR-SP films were formed by solvent-casting. The effect of SP incorporation on material properties, including mechanical, shape memory, thermal, and cytocompatibility, was studied. Mechanochromic behavior was analyzed by straining the films and imaging using a camera and fluorescence microscopy. We also employed a previously developed bacterial protease-responsive PUR SMP to confirm that SP incorporation enables simultaneous shape and color changes in the presence of bacteria. Strained samples showed increased fluorescence (up to 56%, p < 0.05), which was reversed upon shape recovery. Mechanochromic behavior was affected by the hard-to-soft segment ratio of the PUR, SP concentration, and strain percentage. Bacteria-responsive PURs with SP showed reduction in fluorescence and complete biofilm removal after incubation with Staphylococcus aureus for 24 h, which conveyed the potential to use SP in PURs as a molecular force probe with color-based bacteria detection. This technology could be expanded to include a range of other stimuli-responsive functionalities in future work to enable shape and color changes based on environmental cues.
Antifungal Activity, Cytocompatibility, and Wound Healing Potential of Novel Mucoadhesive Formulations for Oral Drug Delivery.
Sugio CYC, Martin V, Gonçalves LMD … +4 more , Ferrari PC, Urban VM, Neppelenbroek KH, Fernandes MH
J Biomed Mater Res A · 2025 Oct · PMID 40977589 · Publisher ↗
Conventional treatments for oral candidiasis often fail due to the complexities of the oral environment and the increasing antifungal drug resistance. Therefore, there is a growing demand for new therapies that optimize...
Conventional treatments for oral candidiasis often fail due to the complexities of the oral environment and the increasing antifungal drug resistance. Therefore, there is a growing demand for new therapies that optimize drug bioavailability, allowing for lower therapeutic doses while enhancing cytocompatibility, maintaining antifungal, anti-inflammatory, and wound healing efficacy. This study investigated the antifungal activity, cytocompatibility, wound healing potential, and mucosal adhesion of novel mucoadhesive formulations containing nystatin (NYS) or chlorhexidine (CHX) complexed with β-cyclodextrin (βCD), compared with the drug-free formulation (GEL) and the standard treatment with 2% miconazole gel (DK-Daktarin). Efficacy against Candida albicans was evaluated by measuring the metabolic activity, whereas cytocompatibility with human gingival fibroblasts (HGFs) was analyzed for viability, morphology, lactate dehydrogenase (LDH) release, and apoptosis. Additionally, wound healing potential was investigated by assessing cell migration efficacy, anti-inflammatory activity, and reactive oxygen species (ROS) scavenging activity. Mucoadhesion was evaluated using mucin discs and a texture analyzer. Mucoadhesive gels containing βCD-complexed NYS or CHX exhibited significantly higher antifungal activity when compared to the GEL and DK groups (p < 0.05). Compared to fibroblast control cultures, those exposed to drug-complexed gels exhibited similar viability (p > 0.05) and morphological parameters, lower LDH release (p < 0.05), and similar apoptosis rates (p > 0.05). Additionally, exposure to the βCD-modified gels was associated with complete wound closure (p > 0.05), significant anti-inflammatory effect, with downregulation of pro-inflammatory gene expression (p < 0.05), and higher ROS scavenging activity (p < 0.05). The developed formulations showed no difference in mucoadhesiveness (p > 0.05), which was superior to that of DK (p < 0.05). Therefore, the proposed drug-complexed mucoadhesives are promising therapeutic options for oral candidiasis.
Cobalt-Doped Monetite-Induced Biomimetic Hypoxia Camouflages Osteogenic Healing Microenvironment.
de Almeida GS, Pinto TS, Suter LC … +7 more , da Silva Feltran G, Carra MGJ, Moraes JF, Corrêa DRN, Filho PNL, Saeki MJ, Zambuzzi WF
J Biomed Mater Res A · 2025 Oct · PMID 40977586 · Publisher ↗
To address developing novel biomimetic material able to camouflage osteogenic healing microenvironment, this study looked to synthesize and characterize a cobalt-doped monetite (CoCaP). After synthesizing, the samples we...
To address developing novel biomimetic material able to camouflage osteogenic healing microenvironment, this study looked to synthesize and characterize a cobalt-doped monetite (CoCaP). After synthesizing, the samples were subjected to physicochemical and biological characterization a comprehensive structural analysis encompassing a suite of complementary techniques. Previously, our data show a validation and reveal distinct structural alterations from cobalt doping. Biologically, Co-doped monetite had no cytotoxic effects on osteoblasts up to 7 days; rather, it contributed to osteoblast adhesion and migration, here estimated by carrying out a wound healing assay. Thereafter, we have linked this phenomenon to an upregulation of cyclin-dependent kinases (CDKs) genes, and it was hypothesized to be related to the dynamic adhesion-related machinery requiring the upregulation of integrins, focal adhesion kinase (FAK), and Src. Complementarily, osteoblast differentiation was also investigated, and our data clearly show a strong stimulus of osteogenic phenotype, once it was shown a significantly increased upregulation of both classical osteogenic transcription factors Runx2 and Osterix, both in response to Co-doped monetite. Additionally, we observed extracellular matrix (ECM) remodeling requiring the activities of matrix metalloproteinase 9 (MMP9) zymogens, suggesting effective collagen turnover along osteoblast differentiation and mineralization. Collectively, our findings show the biological impact of Co-doped monetite on the osteogenic phenotype of pre-osteoblasts. Notably, cobalt-doped monetite induces biomimetic hypoxia, and it recapitulates relevance on the osteogenic phenotype required for the bone healing microenvironment. Thus, Co-doped monetite emerges as a biomimetic and "smart" advanced material for promising applications in bone injuries or the bioactive surface of dental implants in the future.
Hyaluronic Acid/Type I Collagen Hydrogels With Tunable Physicochemical Properties Using Diels-Alder Click Chemistry.
Fatima R, Almeida B
J Biomed Mater Res A · 2025 Oct · PMID 40977585 · Publisher ↗
Hydrogels that combine mechanical tunability with biochemical relevance are essential for engineering tissue-mimetic scaffolds for tissue engineering and regenerative medicine applications. In this study, we present for...
Hydrogels that combine mechanical tunability with biochemical relevance are essential for engineering tissue-mimetic scaffolds for tissue engineering and regenerative medicine applications. In this study, we present for the first time a tunable hydrogel platform formed via Diels-Alder bioorthogonal click chemistry using furan-functionalized hyaluronic acid (HA-furan), furan-functionalized type I collagen (Col-furan), and bis-maleimide-functionalized polyethylene glycol (mal-PEG-mal). Hydrogels were fabricated at furan:maleimide molar ratios of 1:0.5, 1:1, and 1:2.5 and gelled under physiological conditions for 24 h without the need for catalysts or initiators. Material characterization revealed that this mechanism fabricated predominantly elastic hydrogels, where the 1:1 M ratio hydrogel was the most stable and had the highest mechanical properties, with a Young's modulus that was 2.1-fold and 4.7-fold larger than the 1:0.5 and 1:2.5 M ratio hydrogels, respectively. Further analysis revealed that hydrogel stability and performance were predominantly controlled by hydrogel structure (amorphous vs. crystalline) and crosslinking density. This enhanced mechanical stability and performance were also synergized with enhanced bioactivity from the incorporation of Col, which introduced native Arg-Gly-Asp (RGD) motifs that support cell interactions. Overall, this bioactive yet biomechanically stable hydrogel system provides a tunable platform for engineering extracellular matrix-inspired biomaterials with broad potential for soft tissue repair and regenerative medicine applications.
Quantitative Analysis of Glutathione Utilizing Highly Luminescent Gold Nanoclusters.
He W, Qu Y, Wu S … +4 more , Lim SF, Mo L, Mou H, Song J
J Biomed Mater Res A · 2025 Oct · PMID 40977580 · Publisher ↗
Glutathione (GSH), a pivotal regulator of cellular redox homeostasis, requires precise monitoring for clinical diagnostics. This work develops bovine serum albumin-templated gold nanoclusters (BSA-AuNCs) through in situ...
Glutathione (GSH), a pivotal regulator of cellular redox homeostasis, requires precise monitoring for clinical diagnostics. This work develops bovine serum albumin-templated gold nanoclusters (BSA-AuNCs) through in situ chloroauric acid reduction, exhibiting orange fluorescence (λ = 610 nm) with 35.8% quantum yield. Systematic evaluation of pH-dependent and time-resolved quenching behavior revealed optimal GSH detection at physiological pH 7.4 within 3 min. The nanozyme demonstrated linear responsivity from 10 nM to 3 μM (Limit of Detection, LOD = 8.7 nM) and validated applicability in biological matrices (urine/serum) with 98.0%-103.3% recovery rates. This photoluminescent platform enables reliable GSH biomarker quantification, advancing point-of-care testing for oxidative stress disorders.
Nanostructured Polyurethane-Collagen Hydrogels: Bioactive Crosslinked Networks for Enhanced Wound Healing.
León-Campos MI, Claudio-Rizo JA, Cobos-Puc LE … +4 more , Cabrera-Munguía DA, Rubio-Rios A, Oyervides-Muñoz E, Velázquez-Arrellano A
J Biomed Mater Res A · 2025 Oct · PMID 40977573 · Publisher ↗
Nanostructured polyurethanes (nPUs) are promising materials for biomedical applications due to their mechanical strength, controlled degradation, and bioactivity. In this study, collagen-based hydrogels were developed us...
Nanostructured polyurethanes (nPUs) are promising materials for biomedical applications due to their mechanical strength, controlled degradation, and bioactivity. In this study, collagen-based hydrogels were developed using nPUs synthesized from ethoxylated glycerol and either hexamethylene diisocyanate (HDI) or isophorone diisocyanate (IPDI), functionalized with L-tyrosine (T). These nPUs were incorporated at 15% and 30% by weight into porcine dermis collagen. The HDI-based nPUs (HDI-T), with particle sizes between 6 and 58 nm, achieved high crosslinking densities (> 90%) and superabsorbent capacities (> 6000%), which accelerated gelation under physiological conditions. The resulting hydrogels showed enhanced elasticity and resistance to deformation-critical for wound healing. Structural analysis revealed semi-crystalline and rough surfaces. Hydrogels crosslinked with HDI-T (P(HDI-T)) exhibited excellent hydrolytic stability at pH 8.5 and in simulated body fluids (SBF), as well as reduced enzymatic degradation. These systems allowed for sustained release of methylene blue at both physiological and acidic pH, while ketorolac release was more pronounced in acidic conditions. Biologically, the hydrogels were non-hemolytic and biocompatible, promoting monocyte and fibroblast metabolic activity. Notably, P(HDI-T30) hydrogels stimulated the release of Interleukin-10 (IL-10), contributing to inflammation modulation. In addition, they exhibited potent antibacterial activity, inhibiting Escherichia coli (E. coli) growth by up to 150% and Staphylococcus aureus (S. aureus) by 60% compared to controls. In vivo, complete wound closure was observed by Day 17, with regenerated tissue rich in collagen. These findings demonstrate the potential of nPU-collagen hydrogels as multifunctional biomaterials for advanced wound healing, combining mechanical integrity, controlled drug release, antibacterial efficacy, and immune modulation.
In Vitro Characterization of Biodegradable Polyurethane Foams With Facile Gelatin Modification for Traumatic Wound Hemostasis and Regeneration.
Petryk NM, Monroe MBB
J Biomed Mater Res A · 2025 Oct · PMID 40977564 · Full text
Polyurethane (PUr) foams are widely explored for embolic, hemostatic, and tissue engineering applications. Their tunable pore structure, mechanical properties, and degradation rates make PUr foams ideal scaffolds for thr...
Polyurethane (PUr) foams are widely explored for embolic, hemostatic, and tissue engineering applications. Their tunable pore structure, mechanical properties, and degradation rates make PUr foams ideal scaffolds for thrombus formation and cell infiltration. Despite their embolic and hemostatic efficacy, PUrs are entirely synthetic, which limits their long-term healing capacity to facilitate tissue regeneration. To improve PUr-driven healing, this work explores the facile modification of biodegradable PUr foams with bioactive gelatin through simple physical and chemical incorporation methods accomplished post-foam fabrication. The gelatin-modified PUr foams had increased platelet interactions and quicker clotting times than the unmodified PUr foams due to the procoagulant nature of gelatin. Furthermore, the gelatin-modified foams had significantly improved cell attachment, spreading, and proliferation of fibroblasts on foam pores, which could translate to enhanced wound repair through tissue migration into the PUr scaffold. Overall, the simple modification of biodegradable PUr foams with bioactive gelatin can significantly improve healing outcomes in traumatic wounds and various regenerative tissue applications.
Coaxial Electrospray of Nanodrug-Loaded Porous Polylactic Acid/Poly(Ethylene Oxide) Core-Shell Microparticles for Intrapulmonary Drug Delivery.
Wang C, Guo D, Luo J … +1 more , Zhou Y
J Biomed Mater Res A · 2025 Sep · PMID 40938284 · Full text
Biocompatible nano-to-microscale particles offer significant advantages for therapeutic applications, particularly in targeted and sustained drug delivery for lung diseases such as chronic obstructive pulmonary disease (...
Biocompatible nano-to-microscale particles offer significant advantages for therapeutic applications, particularly in targeted and sustained drug delivery for lung diseases such as chronic obstructive pulmonary disease (COPD). This study focuses on the fabrication of porous core-shell microparticles encapsulating bioactive telodendrimer (TD) nanodrug carriers using electrospray technology. The microparticles were designed to enhance pulmonary drug delivery by optimizing particle size (1-5 μm) and morphology for deep lung deposition and controlled drug release. The effects of solution viscosity and surface tension on microparticle formation were systematically investigated. Results demonstrated that higher polymer concentration and controlled electrospray parameters yielded spherical microparticles with uniform porosity, essential for sustained drug release. Surfactant addition reduced particle size and enhanced pore formation but introduced challenges such as morphological variability. In vitro cytotoxicity, hemolysis, and drug release studies confirmed the biocompatibility and therapeutic potential of the fabricated microparticles. The findings highlight the promise of electrospray-derived core-shell microparticles for non-invasive COPD treatment, warranting further exploration into polymer-solvent interactions and formulation refinements for optimized drug delivery.
Targeting Cell-Matrix Induced Chemoresistance With Regorafenib in a 3D Model of Osteosarcoma.
Rao RR, Huang MS, Zhang D … +6 more , Huerta-López C, Long C, Rodriguez GA, Mozipo EAT, Sagi S, Heilshorn SC
J Biomed Mater Res A · 2025 Sep · PMID 40938276 · Full text
Over the past four decades, there has been little advancement in treatment strategies for osteosarcoma (OS), the predominant primary bone tumor in the pediatric patient population. Current therapy involves multiple round...
Over the past four decades, there has been little advancement in treatment strategies for osteosarcoma (OS), the predominant primary bone tumor in the pediatric patient population. Current therapy involves multiple rounds of chemotherapy and surgical resection, which are associated with significant morbidity and suboptimal survival rates. A key challenge in developing new treatments is the difficulty in replicating the OS tumor microenvironment, particularly cell interactions with the extracellular matrix (ECM). This study uses an in vitro model of OS to investigate the cell response to collagen (COL) type I, the primary component of the OS ECM. After 7 days of culture within three-dimensional COL hydrogels, OS cells displayed a more elongated cellular morphology and reduced sensitivity to the standard chemotherapy used for OS treatment compared to cells grown on two-dimensional substrates. To test whether this model could be used to study treatment strategies used for high-risk OS patients, we applied a metronomic regimen combining regorafenib, a multi-tyrosine kinase inhibitor, with front-line chemotherapy to overcome cell-matrix induced chemoresistance. We identified overexpression of the ATP-binding cassette transporter ABCG2, a drug efflux pump, as a potential mechanism of resistance in 3D culture. Regorafenib's inhibitory effect on ABCG2 suggests a mechanistic basis for its ability to restore chemosensitivity in 3D culture. Altogether, these findings highlight the importance of cell-matrix interactions in in vitro OS models, provide valuable insights into a matrix-induced mechanism of OS chemoresistance, and suggest an approach to its treatment.
Therapeutic Effect of a Composite Acellular Matrix/Hyaluronic Acid Thermosensitive Hydrogel for the Interstitial Cystitis/Bladder Pain Syndrome in a Rat Model.
Liu H, Guo W, Zhang J … +4 more , Tang W, Wang F, Zhang J, Zhang P
J Biomed Mater Res A · 2025 Sep · PMID 40899624 · Publisher ↗
This study investigated the therapeutic effects of a composite small intestinal submucosa decellularized extracellular matrix/hyaluronic acid (HA)-incorporated thermosensitive hydrogel (HA-Gel) on interstitial cystitis (...
This study investigated the therapeutic effects of a composite small intestinal submucosa decellularized extracellular matrix/hyaluronic acid (HA)-incorporated thermosensitive hydrogel (HA-Gel) on interstitial cystitis (IC) in rats. The HA-Gel was fabricated using rabbit small intestinal submucosa-derived extracellular matrix as a thermosensitive scaffold combined with HA, and an IC rat model was established using the UPK3A65-84 peptide. Rats were divided into five groups: IC group, IC + HA group, IC + Gel group, IC + HA-Gel group, and a non-modeled control group. After 14 days of treatment, urodynamic analysis revealed that the HA, IC + Gel, and IC + HA-Gel groups exhibited significantly increased interval voiding times and maximum bladder capacities compared to the IC group, with the most pronounced improvement observed in the IC + HA-Gel group (p < 0.01). Histopathological evaluation revealed reduced mucosal edema, inflammatory cell infiltration, and mucosal denudation in all treatment groups, particularly in the IC + HA-Gel group (p < 0.01). Mast cell infiltration was also markedly suppressed by HA-Gel (p < 0.01). Immunofluorescence and molecular analyses further indicated that HA, Gel, and HA-Gel effectively downregulated the expression levels of CD3, ICAM-1, TNF-α, IFN-γ, IL-1β, IL-6, and TRPM8 in bladder tissues, with the most significant reductions observed in the IC + HA-Gel group (p < 0.01). Notably, both Gel and HA-Gel remained detectable in bladder tissues for over 14 days post-administration. In conclusion, HA-Gel not only improves voiding function and bladder capacity in IC rats but also suppresses inflammatory responses, demonstrating promising therapeutic potential and providing new insights for the clinical management of IC/bladder pain syndrome (BPS).
Implantable Medical Devices, Biomaterials, and the Foreign Body Response: A Surgical Perspective.
Kalashnikov N, Barralet J, Vorstenbosch J
J Biomed Mater Res A · 2025 Sep · PMID 40899623 · Publisher ↗
Implantable medical devices improve quality of life and reduce mortality by restoring the form and function of the human body. Their biomaterial surface components in contact with tissues are, however, susceptible to the...
Implantable medical devices improve quality of life and reduce mortality by restoring the form and function of the human body. Their biomaterial surface components in contact with tissues are, however, susceptible to the host's foreign body response, which drives inflammation and implant fibrous encapsulation. When dysregulated, this response causes implant-related patient morbidity and device failure, ultimately requiring revision surgery. Here, we review the roles that the biomaterial, the host, and the implantation surgery play in the foreign body response. Taking commonly-used implantable medical devices as examples, we first describe the foreign body response; then, we examine the factors influencing it, and finally, we propose ideas of how it can be controlled perioperatively in an attempt to minimize implant-related complications.
Efficacy of 3D-Printed Bioactive Glass Tetrahedral Particles for Vertical Bone Regeneration: A Comparative Study.
Wang W, Ai L, Zheng L … +5 more , Chen D, Aversa R, Apicella A, Wang C, Fan Y
J Biomed Mater Res A · 2025 Sep · PMID 40884429 · Publisher ↗
This study was designed to systematically evaluate the osteogenic efficacy of 3D-printed tetrahedral bioactive glass particles in vertical bone regeneration and compare their performance with that of conventional bone su...
This study was designed to systematically evaluate the osteogenic efficacy of 3D-printed tetrahedral bioactive glass particles in vertical bone regeneration and compare their performance with that of conventional bone substitute materials. In this investigation, 3D tetrahedral bioactive glass particles were fabricated using digital light processing (DLP) additive manufacturing technology. The structural integrity and chemical composition of the particles were characterized by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and X-ray diffraction (XRD) to confirm their conformity to design specifications. Additionally, three commercially available bone substitutes-Bio-Oss, PerioGlas, and Osteon-were employed as control materials for comparative analysis. In the experimental phase, four types of particulate materials were loaded into titanium buckets, which were then implanted on the calvarial surface of New Zealand white rabbits with surgically drilled cortical perforations at the implantation site. Micro-computed tomography (micro-CT) and histological evaluations were performed at 4 weeks and 12 weeks post-implantation. The results demonstrated that at 4 weeks, the height of new bone formation induced by the 3D-printed tetrahedral bioactive glass particles was 4.67 ± 0.34 mm, with a new bone proportion of 12.42% ± 3.81% and a new bone marrow proportion of 11.58% ± 1.63%. By 12 weeks, no statistically significant differences were observed among the groups in terms of new bone height, new bone proportion, or new bone marrow proportion. However, the 3D-printed particles exhibited a more homogeneous distribution of newly formed bone tissue. The osteogenic efficacy of 3D-printed tetrahedral bioactive glass particles in vertical bone regeneration is comparable to that of traditional bone substitute materials. However, their distinctive tetrahedral structure offers superior uniformity in bone growth. These results indicate that 3D printing technology holds promise for the development of bone substitute materials and merits further optimization as well as clinical translation.
3D-Printed Precision Porous Scaffolds Promote Healing In Vivo.
Chen G, Creason S, Chen N … +5 more , Kirkham A, Zhen L, Zhang S, Wu K, Ratner B
J Biomed Mater Res A · 2025 Sep · PMID 40884427 · Publisher ↗
Precision porous scaffolds hold promise for tissue engineering and regenerative medicine due to their ability to support cell ingrowth and vascularization and mitigate the foreign body reaction (FBR). In previous work, w...
Precision porous scaffolds hold promise for tissue engineering and regenerative medicine due to their ability to support cell ingrowth and vascularization and mitigate the foreign body reaction (FBR). In previous work, we demonstrated that vat photopolymerization 3D printing enables the fabrication of porous scaffolds with 40 μm interconnected cubical pores. This study aims to do a preliminary evaluation of cellular responses and the FBR to 3D-printed scaffolds with 40 μm cubical pores, in comparison with template-fabricated spherical pores (optimized for healing) and non-porous slabs (negative control). The results indicate that porous scaffolds, regardless of pore geometry, outperform non-porous structures in mitigating the FBR, promoting tissue regeneration, and triggering vascularization. This is the first paper demonstrating the pro-healing property of high-resolution 3D-printed 40 μm cubical pore scaffolds. These findings underscore the potential of 3D-printed porous scaffolds to advance patient-specific therapies, support soft (such as brain and blood vessel) and hard tissue (such as bone) repair, and improve healing outcomes in regenerative medicine applications.
Gyroid-Structured Scaffolds Guide Uniform Ossification and Modulate Vascular Morphology During Rat Calvarial Bone Defect Regeneration.
Xian G, Charbonnier B, Bensidhoum M … +8 more , Potier E, Margottin M, Sheng P, Chappard C, Petite H, Anagnostou F, Marchat D, Logeart-Avramoglou D
J Biomed Mater Res A · 2025 Sep · PMID 40884424 · Publisher ↗
Bone repair procedures rely on osteoconductive material scaffolds that guide and promote bone ingrowth through their architecture. This study investigated how the bone formation and vascularization are modulated within g...
Bone repair procedures rely on osteoconductive material scaffolds that guide and promote bone ingrowth through their architecture. This study investigated how the bone formation and vascularization are modulated within gyroid macroporous scaffolds during the regeneration of rat calvarial bone defects. It compared scaffold-guided regeneration to spontaneous healing through 3D analysis of both ossification and vascularization. Two disc-shaped bioceramic scaffolds with either wide or narrow porous geometries were designed and fabricated to facilitate or limit bone ingrowth. While overall ossification dynamics were similar regardless of repair efficacy, scaffold presence modulated the ossification pattern, promoting bone formation throughout by conduction. The scaffolds also influenced vascular network morphology but not its density. Notably, 3D imaging revealed a negative correlation between vascularization and bone formation in scaffold-filled defects, while no correlation was found in empty defects. This result suggests that ossification during calvarial regeneration relies on additional pro-osteogenic factors beyond robust vascularization. These insights are valuable for optimizing scaffold-based strategies to enhance bone regeneration in calvarial defects.
Multifunctional Characteristics of Cu/Zn Co-Doped Hydroxyapatite: Enhanced Electrical, Surface, and Biocompatibility.
Ganesh MD, Manickasamy MK, Joel P … +3 more , Kalyani D, Kunnumakkara AB, Dobbidi P
J Biomed Mater Res A · 2025 Aug · PMID 40815674 · Publisher ↗
Developing multifunctional biomaterials with both electrical and biological properties is crucial for next-generation biomedical platforms. This study looks into how Cu/Zn co-doping affects the structural, electrical, an...
Developing multifunctional biomaterials with both electrical and biological properties is crucial for next-generation biomedical platforms. This study looks into how Cu/Zn co-doping affects the structural, electrical, and biological performance of hydroxyapatite (CaZnCu(PO)(OH); x = y = 0.2-1.2), which was synthesized through a solid-state reaction. Among the samples, the CZ6 composition (x = y = 0.6) showed the best properties. It had a single-phase hexagonal structure, a nanoscale crystallite size of about 32 nm, a d-spacing of 0.27 nm along the (112) plane, and a grain size that ranged from 300 to 1200 nm while still keeping the proper composition. Electrical tests showed that CZ6 had the highest dielectric constant of 14.06 at 1 MHz. It maintained a low and stable loss tangent (~0.01), lower grain boundary resistance, and improved AC conductivity (from 10 to 10 S/cm), indicating better charge transport. These electrical enhancements correlate strongly with improved biological responses. CZ6 displayed strong apatite formation in simulated body fluid, the highest BSA protein adsorption of 25.05 μg/mL, and an optimized zeta potential of -30.54 mV, which facilitates enhanced biomolecular interactions. Cytocompatibility tests with PSVK-1 (skin keratinocytes) and Wi-38 (lung fibroblasts) confirmed that cell viability remained high at all concentrations. While higher levels of dopants led to the formation of secondary phases and diminished biological responses, CZ6 kept a good balance between electroactivity and biofunctionality. These findings make CZ6 a promising electroactive bioceramic for bone tissue engineering, smart implant coatings, and bioelectret scaffolds, where combining electrical responsiveness with cellular compatibility is important.
Design of a Corrugated Vascular Graft with Enhanced Compliance and Kink Resistance.
Robinson A, Duran JSH, Jiang D … +6 more , Leung J, Laude M, Nkansah A, Guo L, Timmins L, Cosgriff-Hernandez E
J Biomed Mater Res A · 2025 Aug · PMID 40815669 · Publisher ↗
The development of a small-diameter vascular graft for coronary artery bypass grafting necessitates a balance of key biomechanical properties to prevent failure. Prior iterative design of a multilayer vascular graft achi...
The development of a small-diameter vascular graft for coronary artery bypass grafting necessitates a balance of key biomechanical properties to prevent failure. Prior iterative design of a multilayer vascular graft achieved arterial compliance-matching to prevent failure due to intimal hyperplasia while retaining sufficient burst pressure and suture retention strength. Although promising, graft kinking prevented long-term evaluation in vivo. To enhance kink resistance, a post-electrospinning molding method was developed to impart a corrugated geometry. Corrugations enhance kink resistance during bending through expansion and folding of the pleats to prevent ovalization and subsequent buckling. The corrugated graft significantly improved kink resistance with kink radii similar to synthetic grafts used in the clinic. In contrast to prior literature, the corrugated grafts displayed compliance values in the range of arterial values (10.4%/mmHg × 10 ± 0.3%/mmHg × 10) for improved graft-artery compliance-matching. A finite element (FE) model of compliance was used to elucidate the effect of corrugated geometry on graft compliance. The FE-predicted compliance values agreed well with experimental results and demonstrated an increase in Lagrange strain magnitude of the corrugated valleys that was correlated with a higher luminal compliance. To ensure clinical utility of corrugated grafts, candidate grafts were tested for suture retention strength, burst pressure, and stability under physiological loading. The corrugated graft retained biomechanical properties above or similar to reported values of the saphenous vein, demonstrating suitability for implantation. Finally, no significant change in graft dimensions demonstrated stability of the post-fabrication corrugation geometry after 30 days under pulsatile flow. A small-diameter vascular graft with this unique combination of biomechanical properties has the potential to improve long-term outcomes in coronary artery bypass graft procedures.
Fish Collagen-Based Bilayer Composite Scaffold Functionalized With Fibrin/Hydroxyapatite/Sodium Citrate for Osteochondral Tissue Engineering-In Vitro and In Vivo Studies.
Vijayalekha A, Anandasadagopan SK, Gopal T … +3 more , Durai S, Anumaiya V, Pandurangan AK
J Biomed Mater Res A · 2025 Aug · PMID 40808612 · Publisher ↗
Osteochondral defects (OCDs) present significant clinical challenges, necessitating scaffolds that effectively regenerate both cartilage and subchondral bone. We developed a bilayer scaffold using fish collagen extracted...
Osteochondral defects (OCDs) present significant clinical challenges, necessitating scaffolds that effectively regenerate both cartilage and subchondral bone. We developed a bilayer scaffold using fish collagen extracted from Catla catla skin to overcome the limitations of conventional biomaterials, such as mammalian collagen and synthetic polymers, which often suffer from immunogenic risks, poor bioactivity, or inadequate structural integration. The scaffold is comprised of collagen/fibrin (CC/FIB) for the articular cartilage layer and collagen/sodium citrate/hydroxyapatite (CC/NAC/HAP) for the subchondral bone layer, which is cross-linked with citric acid. Physicochemical characterization confirmed scaffold integration, enhanced thermal stability, and a porous architecture. The scaffold demonstrated optimal porosity (63.12%), degradation (62.08% over 28 days), superior swelling potential, and enhanced bio-mineralization in simulated body fluid. In vitro studies using MG-63 osteoblast-like cells and MC3T3-E1 cells showed high biocompatibility, increased alkaline phosphatase activity, and enhanced calcium deposition (33.73 ± 0.53 μg/mg of protein at 21 days). Gene expression analysis revealed upregulation of osteogenic (COL I ~23-fold, RUNX-2 ~15-fold, OCN ~8-fold) and chondrogenic (COL II ~12-fold, SOX-9 ~10-fold, ACAN ~6-fold) markers, confirming osteochondral regeneration potential. In vivo studies involving the implantation of 3 mm femoral trochlear OCDs in albino Wistar rats (n = 3 per group) resulted in substantial bone and cartilage regeneration, with complete defect closure by 12 weeks. Radiographic and histological assessments at 4, 8, and 12 weeks confirmed well-organized osteochondral repair, demonstrating superior regenerative capability compared to control groups. This study establishes the novelty of the fish collagen-based bilayer scaffold as a promising candidate for osteochondral tissue engineering, supporting effective cartilage and subchondral bone regeneration in OCD treatment.
Development and Characterization of Hyaluronic Acid Microgels for Neural Regeneration Applications.
Hickey KN, Grassi SM, Bjorklund GR … +6 more , Fumasi FM, Veldhuizen J, Witten AM, Nikkhah M, Holloway JL, Stabenfeldt SE
J Biomed Mater Res A · 2025 Aug · PMID 40787877 · Full text
Delivery of therapeutic compounds via biomaterial systems has shown promise for tissue regeneration following central nervous system (CNS) injuries. Stromal cell-derived factor-1a (SDF-1a) modulates progenitor cell recru...
Delivery of therapeutic compounds via biomaterial systems has shown promise for tissue regeneration following central nervous system (CNS) injuries. Stromal cell-derived factor-1a (SDF-1a) modulates progenitor cell recruitment to neural injury sites and may contribute to neural repair. However, SDF-1a has a short half-life and requires a delivery system to both protect and sustain its release. Here, we sought to develop a drug delivery platform capable of releasing SDF-1a in a controlled fashion while minimizing inflammation. We used modified hyaluronic acid and microfluidics to generate monodisperse microgels. Characterization of these microgels included size, tunability, degradation, and controlled release properties. Finally, we delivered SDF-1a-loaded microgels to a mouse model of traumatic brain injury at 7 days post-injury and assessed their impact on neural progenitor cell recruitment and astrogliosis. The microfluidic system generated highly monodisperse microgels that successfully encapsulated a matrix metalloproteinase (MMP)-cleavable SDF-1a peptide and retained sensitivity to collagenase. Following intracortical injections, the microgels did not exacerbate the astrocytic response compared to saline injections; no significant difference was observed in neural progenitor cell migration patterns compared to controls. Therefore, we developed a biocompatible microgel system that is highly adaptable for biological delivery and may be utilized in brain/neural applications without exacerbating neuroinflammation.
Correction to "Photocrosslinkable and elastomeric hydrogels for bone regeneration".
J Biomed Mater Res A · 2025 Aug · PMID 40778723 · Publisher ↗
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