Materials Science & Engineering C-Materials for Biological Applications最新文献

Oral ulcers affect over 25% of the global population, substantially impairing quality of life. Current therapeutic approaches are limited by challenges such as drug resistance and treatment dependency. Although probiotics have shown promise in mucosal repair, local delivery of anaerobic strains such as Bifidobacterium bifidum remains challenging because oxygen exposure rapidly reduces bacterial viability. Here, we report a sprayable, dynamic Schiff-base gelatin/cellulose hydrogel capable of in situ gelation and microenvironment engineering for the viable delivery of Bifidobacterium bifidum. The reversible imine crosslinking network forms an oxygen-limited, moisture-retaining niche that preserves bacterial viability while enabling uniform mucosal adhesion and deformation tolerance. B. bifidum embedded in the hydrogel exhibited sustained release over 2 h and maintained high activity throughout gelation and degradation. In vitro, the hydrogel and B. bifidum synergistically enhanced fibroblast migration, reduced LPS-induced TNF-α and IL-6 expression, and promoted macrophage polarization toward the M2 phenotype. In vivo, the B. bifidum-loaded hydrogel markedly accelerated oral ulcer closure, improved epithelial regeneration, increased collagen deposition, and elevated α-SMA and collagen I expression. Cytokine profiling confirmed a transition toward a pro-healing microenvironment characterized by decreased TNF-α/IL-6 and increased IL-10 levels. No systemic toxicity was observed. This work demonstrates a microbe-material synergy strategy, where a dynamic covalent hydrogel enables anaerobic probiotic therapy by engineering a protective oxygen-limited microenvironment. The platform offers a clinically translatable approach for managing oral mucosal wounds under complex wet conditions.

Effective cell adhesion under challenging mechanical situations is critical for a vital soft tissue sealing of the transmucosal parts of dental implants and thus essential for oral wound healing. To investigate this process in vitro, we developed a versatile flow chamber model that applies defined shear stress to assess the adhesion strength of relevant cell types. The system focuses mainly on primary human gingival fibroblasts, with preliminary experiments including also gingival keratinocytes. The chamber accommodates standard-sized titanium sample geometries used in projects dedicated to develop surface modifications preventing peri-implantitis. Actual shear stress was determined through computational fluid dynamics software, targeting a central 5 × 5 mm region used for cell seeding. Shear stress ranged from 0.05 Pa (0.4 ml/min) to 0.49 Pa (4 ml/min). Key variables studied included shear stress magnitude and duration of the dynamic phase. We assessed two titanium surface topographies-polished and nanodiamond-coated-to explore the role of nano-roughness in resisting detachment. Results demonstrated that topography significantly influences cell retention, with highest differences observed under 0.36 Pa shear stress for 1 to 2 h of dynamic phase. Furthermore, we adapted the model to simulate wound healing, revealing that surface topography impacts repopulation dynamics. Of two compared arrangements for the co-culture of fibroblasts and keratocytes, either sequential seeding of keratinocytes on top of pre-seeded fibroblast or simultaneously in adjacent regions, we prefer the latter approach for this specific dynamic model. Overall, in all model modifications the nanorough surfaces supported a more stable attachment of both fibroblasts and keratinocytes, with greater shear sensitivity of the keratinocytes. This model offers a reproducible, physiologically relevant platform to evaluate adhesion strength and wound healing, with potential for future application in biomaterial screening and implant design.

Crosslinking is a key step in the production of stable all-natural polymeric scaffolds for tissue engineering, as it slows the degradation and increases the mechanical properties of the material. In this study, we investigate the crosslinking parameters of a natural, anisotropic scaffold produced from gelatine, chitosan and cellulose through a modified freeze drying protocol, with the goal of maintaining the porous architecture of the scaffold while improving its degradation and mechanical strength. Genipin and EDC were selected as the two crosslinking alternatives, while crosslinker concentration and solvent system (ethanol-to-water ratio) were the optimized parameters. The degree of crosslinking was quantified through a 2,4,6-Trinitrobenzene Sulfonic Acid assay, and the scaffolds were further tested for hydrolytic and enzymatic degradation, swelling and mechanical properties. Scaffolds achieve ultimate tensile strength values of up to 4 MPa, in the relevant physiological range for tendon applications, and crosslinking degrees in the range of 70% - 90%. While scaffolds processed with both crosslinkers maintain the desired pore alignment, genipin was the most successful at delaying the degradation of the material, with 85% of the initial mass of the scaffold remaining after 21 days of immersion in PBS. The solvent system of the crosslinking solution was investigated, with varying ratios of ethanol to water, finding that adding water is necessary for optimal swelling, homogeneous crosslinking and low cytotoxicity of the scaffolds, highlighting the importance of this parameter in the genipin crosslinking process. Genipin crosslinked scaffolds were found to be capable of sustaining the attachment and proliferation of tendon derived stem cells up to 21 days in both 21% and 2% oxygen environments, yielding a strong stable scaffold suitable for supporting tendon regeneration in-vitro.