Journal of biomedical materials research. Part A最新文献

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).

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.

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.

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 (Ca_10-x-yZn_xCu_y(PO₄)₆(OH)₂; 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 10⁻⁷ to 10⁻⁶ 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.

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.

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.

Osteoarthritis (OA) is a progressive joint disease that involves damage to the cartilage, inflammation in the synovium, and injury to the subchondral bone, which highlights the need for the creation of novel treatment options. Nevertheless, finding an effective method that combines anti-inflammatory properties with the ability to regenerate cartilage remains a significant challenge. TA@Sr²⁺ is a bioactive coordination complex formed through chelation between tannic acid (TA) and strontium ions (Sr²⁺), exhibiting a hierarchically structured metal-phenolic network. This research presents an innovative strategy utilizing a Macrophage_nex developed from multifunctional TA@Sr²⁺, which promotes chondrogenesis and exhibits strong anti-inflammatory effects. The Macrophage_nex based on TA@Sr²⁺ is constructed by self-assembling a single-cell layer using varying concentrations of TA and Sr²⁺ on RAW264.7 cell surfaces. This Macrophage_nex demonstrates robust biological activity, enhancing chondrocyte proliferation, differentiation, and migration, alongside the upregulation of anabolic genes such as aggrecan (ACAN) and collagen II, while simultaneously inhibiting the expression of catabolic genes like MMP13 in a dose-dependent manner under LPS-induced inflammation. In addition, TA@Sr²⁺ reduces the expression of proinflammatory cytokines (TNF-α and IL-6) in macrophages and promotes their polarization to the anti-inflammatory M2 phenotype. These results suggest that TA@Sr²⁺ has significant promise for treating OA by regulating both chondrogenesis and macrophage polarization simultaneously.