Adipose Collagen Fragment: an Injectable Sustained-release Collagen Scaffold of Adipokines for Preventing Skin Photoaging in Mice

Abstract

Objective: Ultraviolet A (UVA) radiation is the major contributor to skin photoaging, associated with increased collagen degradation and reactive oxygen species expression. Adipokines have been proven as promising therapeutic agents for skin photoaging. However, adipokine therapy is generally limited by the short in vivo release duration and biological instability. Therefore, developing a treatment that provides a sustained release of adipokines and enhanced therapeutic effects is desirable. Methods: Adipose collagen fragment (ACF) was prepared from lipoaspirate and characterized. The injectability, collagen components, and adipokine release pattern of ACF were identified in vitro. Then, we evaluated its therapeutic efficacy by injecting ACF and phosphate-buffered saline, as a control, into the dermis of photoaging nude mice and harvesting skin samples at weeks 1, 2, and 4 after treatment for assessment. The collagen synthesis and collagen degradation in ACF implants were evaluated by immune staining. Dermal thickness, fibroblast expression, collagen synthesis, reactive oxygen species level, antioxidase expression, capillary density, and apoptotic cell number were evaluated by histological assessment, immune staining, and polymerase chain reaction in the skin samples.Results: ACF is the concentrated adipose extracellular matrix collagen fragment without viable cells and can be injected through fine needles. ACF undergoes collagen degradation and promotes neocollagen synthesis in ACF implants. Meanwhile, ACF serves as a sustained-release system of adipokines and exhibits a significantly higher therapeutic effect on mouse skin photoaging compared to controls. ACF increases the dermal thickness, improves fibroblast expression and promotes collagen synthesis. ACF treatment of UVA-irradiated skin reduces reactive oxygen species expression, decreases the number of apoptotic cells, improves capillary density and promotes the expression of antioxidase superoxide dismutase-1, catalase and glutathione peroxidase-1 by sustainedly releasing adipokines.Conclusions: ACF is an adipokines-enriched, sustained-release extracellular matrix collagen scaffold that can prevent UVA-induced skin photoaging in mice. ACF may serve as a novel autologous skin filler for skin rejuvenation applications in the clinic.