Skeletal muscle regeneration using bioactive glass-alginate-cellulose composites

The present study highlights the development of alginate-microcrystalline cellulose scaffolds enhanced with bioactive constituents by a freeze-drying process. Porous composites were internally cross-linked with calcium carbonate. The effect of incorporating bioactive glass with or without gold nanoparticles into the polymer matrix on morphology, porosity, degradation, in vitro behaviour, and cytotoxicity was investigated. Chemical characterization by spectroscopic techniques confirmed the successful crosslinking between biopolymers and bioactive glasses. Fabricated scaffolds exhibited superior in vitro swelling and degradation behaviour, a property radically influenced by the cellulose content. In addition, the cell viability of keratinocytes and cardiomyocytes was also promoted in control and bioactive glass-containing samples, with no observed cytotoxic effects. The in vitro behaviour of the porous scaffolds was monitored after interaction with the simulated biological fluid, and the in vitro biomineralization was confirmed by the development of the apatite layer. Based on the promising in vitro results, composites were subsequently tested in vivo using a volumetric muscle loss model. Histological evaluation of the tibialis anterior volumetric muscle loss injury site revealed the ability of the composites to induce angiogenesis and myotube formation. Within four weeks post-injury, the treated gold nanoparticle-bioactive glass-alginate-cellulose tissue showed nearly complete scaffold degradation and successfully enhanced skeletal myofiber regeneration.