Recombinant Humanized Type III Collagen Enhances Fat Graft Retention by Promoting Angiogenesis and Adipocyte Viability in a Nude Mouse Model

Abstract Background Autologous fat grafting (AFG) is limited by variable long-term retention. Type III collagen (Col III) may support angiogenesis, adipocyte viability, and immunomodulation. Objectives We evaluated whether recombinant humanized type III collagen (rhCol III) improves fat graft survival in a concentration-dependent manner. Methods Human lipoaspirate was mixed 1:1 (v/v) with rhCol III at 0 (normal saline, NS), 2, 4, or 8 mg/mL and grafted subcutaneously to the dorsum of female BALB/c nude mice. At postoperative weeks 1, 2, 4, and 12, we assessed volume retention, histology (H&E), collagen deposition, adipocyte viability, vascularization, and expression of PPARG, CEBPA, VEGFA, and FGF2. RNA-seq at week 2 profiled rhCol III–associated transcriptional changes. In vitro, human ADSC proliferation, adhesion, migration, and adipogenesis were tested under rhCol III exposure. Results rhCol III reduced volume loss from week 2 onward, with maximal retention at 4 mg/mL. Histology showed superior structural integrity at 4 mg/mL. Collagen content increased dose-dependently (greatest at 8 mg/mL). Perilipin 1 and platelet endothelial cell adhesion molecule-1 (CD31) were elevated with rhCol III, with sustained increases at 4 mg/mL, paralleling upregulation of PPARG, CEBPA, VEGFA, and FGF2. In vitro, rhCol III enhanced ADSC proliferation, adhesion, migration, and adipogenesis, optimal at 4 mg/mL. RNA-seq indicated immune, adhesion, and extracellular matrix programs centered on PI3K–Akt and integrin/matrix–receptor signaling. Conclusions rhCol III enhances fat graft retention by promoting angiogenesis, adipocyte viability, and favorable immune remodeling, with an optimal concentration near 4 mg/mL. rhCol III shows promise as a biomaterial adjunct to improve and standardize AFG outcomes.