Journal of biomedical materials research. Part A最新文献

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.

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.

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).