PI3K/Akt pathway-mediated enhancement of bone and vascular regeneration by gelatin/hyaluronic acid/exosome composite scaffold in bone tissue engineering

Tissue engineering (TE) is commonly suggested as a promising remedy for the worldwide shortage of organ donors required for transplantation. Scholars are investigating organic and biocompatible materials as the principal options for regeneration to replicate the natural extracellular matrix. Hydrogels exhibit swift gel formation and outstanding biocompatibility, thus presenting considerable promise in tissue regeneration. The objective of this study was to investigate the role of a novel biomaterial complex, comprising gelatin (Gel), hyaluronic acid (HA) and exosomes (Exo), in promoting bone regeneration and elucidate its underlying molecular mechanism. The experimental results demonstrated that the Gel/HA/Exo complex could significantly enhance the proliferation and differentiation of osteoblasts, as well as the deposition and mineralization of bone matrix. Further mechanistic studies demonstrated that TGF-β in exosomes enhanced the biological activity of osteoblasts by activating the PI3K/Akt pathway, thus promoting the fracture healing process. The results of in vivo experiments indicated that the application of Gel/HA/Exo complexes significantly accelerated the fracture healing rate and improved the quality of healing, exhibiting good biocompatibility and controlled degradation properties. Consequently, the present study concluded that the Gel/HA/Exo complex not only has potential clinical applications, but also provides an important theoretical and experimental basis for the development of novel bone regeneration therapeutic strategies.