Hydroxyapatite microspheres encapsulated within hybrid hydrogel promote skin regeneration through the activation of Calcium Signaling and Motor Protein pathway

Hydroxyapatite (HAp), traditionally recognized for its efficacy in bone regeneration, has rarely been explored for skin regeneration applications. This investigation explored HAp microspheres with distinct physicochemical properties tailored away from conventional bone regeneration parameters, and the capacity promoting skin regeneration and mitigating the aging process were investigated when encapsulated in hyaluronate hydrogels. By benchmarking against well-established dermal fillers like PMMA and PLLA, it was revealed the specific attributes of HAp that were conducive to skin regeneration, providing initial insights into the underlying mechanism. HAp enhanced the fibroblast functionality by triggering minimal adaptive immune responses and enhancing the Calcium Signaling and Motor Protein Signaling pathways. This modulation supported the production of normal collagen fibers, essential for ECM maturation and skin structural integrity. The significant ECM regeneration and remodeling capabilities exhibited by the HAp-encapsulated hybrid hydrogels suggested promising application in facial rejuvenation procedures, potentially making a breakthrough in aesthetic and reconstructive surgery.