Combinatorial Efficacy of Apigenin‐Resveratrol Collagen Bio‐Matrix for Wound Repair and Regeneration in Abnormal Lipid Expansion

Tissue regeneration is critical, particularly in obesity, where abnormal lipid expansion poses significant challenges. Traditional biomaterials struggle to address the complex wound microenvironment caused by impaired lipid metabolism. There is growing interest in enhancing lipolysis by converting the white adipocytes into brown-like adipocytes to improve overall adipose tissue health, but translating these findings into humans is challenging due to the specificity of targeted signalling pathways. In this study, a combination of browning agents was utilised for the development of specialised biomaterials that can parallelly activate angiogenesis and localised browning to promote faster soft tissue regeneration. The combinatorial effects of apigenin and resveratrol-integrated collagen biomatrix were analyzed. Our findings indicate that the engineered AR collagen biomatrix promotes rapid tissue regeneration compared to biomaterials incorporating individual bioactives by enhancing cell attachment, site-specific thermogenesis within subcutaneous fat, and angiogenesis. In an in vivo DIO-C57BL/6 mouse model, tissue repair was observed within 8 days when treated with AR collagen biomatrix, characterized by distinct neo-epidermal formation, new blood vessel growth, increased collagen deposition, and a significant thermogenic transformation of subcutaneous adipose tissue. This research contributes to the development of novel strategies for addressing impaired wound healing associated with metabolic disorders and offers promise for the advancement of biomaterials for clinical use in wound management.