Journal of biomedical materials research. Part A最新文献

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.

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.

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.