Hydrophilic Components as Key Active Ingredients in Adipose-Derived Matrix Bioscaffolds for Inducing Fat Regeneration.

Decellularized adipose-derived matrix (DAM) has emerged as a promising biomaterial for soft tissue reconstruction. However, due to a lack of research on its complex composition, the understanding of the key components in DAM remains limited, leading to inconsistent adipogenic properties and challenges in optimizing preparation methods purposefully. In this study, it is proposed for the first time that DAM comprises two distinct components: hydrophilic (H-DAM) and lipophilic (L-DAM), each with markedly different effects on fat regeneration. It is confirmed that H-DAM is the key component for inducing fat regeneration due to its enhanced cell-cell and cell-scaffold interactions, primarily mediated by the Hedgehog signaling pathway. In contrast, L-DAM exhibits poor cell adhesion and contains more antigenic components, leading to a higher immunoinflammatory response and reduced adipogenesis. In addition, it is found that intracellular proteins, which are more abundant in H-DAM, can be retained as beneficial components due to their hydrophilicity, contrary to the conventional view that they shall be removed. Accordingly, a purified bioscaffold with unprecedented efficacy is proposed for fat regeneration and reduced immunogenicity. This finding provides insights for developing scaffolds for fat regeneration and promotes the realization of xenotransplantation.