A collagen-rich adipose matrix complex promotes supraperiosteal soft tissue regeneration by remodeling the mechanical microenvironment

Soft-tissue regeneration in periosteum-adjacent recipient beds is limited by poor perfusion and an unfavorable mechanical microenvironment. We investigated whether an autologous collagen-rich adipose matrix complex (AMC) could improve graft retention and remodeling in a cranial supraperiosteal model. Compared with Coleman fat, AMC showed greater long-term retention and a more stable remodeling course. AMC grafts developed a more organized collagen-rich architecture with fewer late degenerative changes. CD34-positive cells accumulated earlier and more prominently in AMC grafts, peaking around day 14, while VEGF-associated signals were stronger during early-to-middle remodeling. CD34/PDGFRα and CD31/α-SMA co-staining further supported stromal/progenitor-like cell accumulation and vascular remodeling. Western blotting showed higher or more sustained expression of proteins related to migration and cytoskeletal regulation. To explore temporal molecular changes during AMC remodeling, label-free proteomic analysis comparing day 14 grafts with baseline day 0 identified coordinated changes in extracellular matrix remodeling, cytoskeletal regulation, collagen maturation, and vascular-associated programs. Secretome proteomics under mechanical activation likewise indicated enhanced matrix organization, adhesion-related remodeling, and tissue-repair signaling. Together, these findings suggest that AMC improves supraperiosteal graft retention and is associated with coordinated early cellular, matrix, and vascular remodeling.