Mossy-textured hydroxyapatite-modified poly (lactic-co-glycolic acid) microspheres promote collagen regeneration via calcium/TGF-β and chemokine signaling pathways in soft tissue augmentation

Skin aging resulting from collagen loss induced by endogenous and exogenous stimuli has become an important factor affecting skin aesthetics and quality of life. The use of simple and efficient soft tissue fillers represents an effective approach to promote collagen regeneration and restore soft tissue support. In this study, mossy-textured hydroxyapatite (CaHA)-modified poly (lactic-co-glycolic acid) (PLGA) composite microspheres (CaHA/PLGA) are developed. These microspheres feature a uniform and stable coating of CaHA beads on the surface of PLGA microspheres and possess particle sizes suitable for soft tissue filling (30–60 μm). The CaHA beads impart a highly porous structure, enhanced protein adsorption, and delayed degradation properties to the composite microspheres. Due to the surface modification by CaHA beads, CaHA/PLGA microspheres exhibit improved cell adhesion, proliferation, and low inflammatory response, as well as enhanced collagen deposition. In vivo studies show that, compared to commercial PLLA microspheres, CaHA/PLGA microspheres provide tissue support as long as 12 weeks with degradation stability, and significantly promote collagen network formation, supporting their long-lasting filling performance. Transcriptome sequencing indicates that CaHA/PLGA microspheres enhance calcium/TGF-β and chemokine signaling pathways in adipose-derived stem cells, facilitating cell migration, cytokine production, and extracellular collagen deposition. Overall, mossy-textured CaHA/PLGA microspheres provide a promising new strategy for soft tissue augmentation and reconstruction. Mossy-textured hydroxyapatite-modified poly (lactic-co-glycolic acid) (CaHA/PLGA) microspheres are composed of CaHA beads and PLGA microspheres. The uniform modification with CaHA imparts a high specific surface area, delayed degradation, and excellent cell adhesion properties to CaHA/PLGA microspheres. Without inducing an inflammatory response in macrophages, CaHA/PLGA microspheres activate calcium, TGF-β, and chemokine signaling pathways in adipose-derived stem cells, modulate the tissue microenvironment, and promote collagen deposition by fibroblasts, ultimately achieving enhanced soft tissue augmentation. • Mossy-textured CaHA/PLGA microspheres for soft tissue augmentation are fabricated via a simple, scalable process. • CaHA beads coat PLGA microspheres uniformly, slowing degradation and boosting adhesion and ECM deposition. • Compared with commercial PLLA, CaHA/PLGA significantly enhance collagen regeneration and soft tissue augmentation at 12 weeks. • CaHA/PLGA microspheres activate Ca/TGF-β and chemokine signaling pathways in ADSCs to soft tissue augmentation.