An Adipose-Derived Injectable Sustained-Release Collagen Scaffold of Adipokines Prepared Through a Fast Mechanical Processing Technique for Preventing Skin Photoaging in Mice

Abstract

Ultraviolet A (UVA) radiation is the major contributor to skin photoaging, associated with increased collagen degradation and reactive oxygen species (ROS) 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. In this study, we developed a novel mechanical processing technique to extract adipose tissue-derived ECM components, named the “adipose collagen fragment” (ACF). The physical characterization, injectability, collagen components, residual DNA/RNA and adipokine release pattern of ACF were identified in vitro. L929 cells were treated with ACF or phosphate-buffered saline for 24 h after UVA irradiation in vitro. The expression of senescence-associated xβ-galactosidase (SA-β-gal), ROS and antioxidase were investigated. 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 content of adipokines released from ACF was identified in vivo. The collagen synthesis and collagen degradation in ACF implants were evaluated by immune staining. Dermal thickness, fibroblast expression, collagen synthesis, ROS level, antioxidase expression, capillary density, and apoptotic cell number were evaluated by histological assessment, immune staining, and polymerase chain reaction in the skin samples. We demonstrated that ACF is the concentrated adipose extracellular matrix collagen fragment without viable cells and can be injected through fine needles. The lower expression of SA-β-gal, ROS and higher expression of antioxidase were observed in the ACF-treated group. 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 by enhancing angiogenesis, antioxidant abilities, antiapoptotic activities, and collagen synthesis through sustainedly releasing adipokines. To sum up, 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.

Macrophage‐mediated extracellular matrix remodeling after fat grafting in nude mice

“…Meanwhile, different types of signaling molecules exist within the ECM scaffold and can cause active substances associated with the ECM to be released and regulate biological responses in accordance with neighboring and distant cues 53,54 . Our previous study proved that adipose collagen fragments contained a large number of bioactive substances and could serve as a sustained‐release system during the degradation process to prevent skin aging by improving fibroblast viability, angiogenesis, and ECM synthesis 55 . Therefore, bioactive substances resulting from graft‐derived ECM degradation may contribute to the subsequent ECM synthesis and adipocyte regeneration 56…”

Combined use of autologous sustained-release scaffold of adipokines and acellular adipose matrix to construct highly vascularized, mature, engineered adipose tissue

“…ACF was extracted from fresh lipoaspirate according to our previously established protocol. 23,24 The lipoaspirate was washed and centrifuged (sterilized saline, at 1200 g for 3 minutes). The centrifuged fat was homogenized for 1 minute (at 30,000 rpm) in an ACF extractor (Shanghai Tiangong Instruments Co., Ltd., Shanghai, People’s Republic of China).…”

“…21,22 Thus, we recently developed a novel mechanical method to extract adipose-derived extracellular matrix (ECM) [referred to as the “adipose collagen fragment” (ACF)], which has proven to be an adipokine-enriched, sustained-release ECM collagen scaffold. 23,24 We hypothesized that the combination of AAM and ACF would effectively promote the formation of mature adipose tissue in vivo. To verify this hypothesis, the protein components of ACF and AAM were comparatively analyzed using proteomic techniques.…”

Collagen study advances for photoaging skin

“…Adipocollagen fragment (ACF), a collagen scaffold rich in adipokines and capable of slowing ECM release, was also shown to have a disproportionately more significant therapeutic impact on mouse skin photoaging, the ability for antioxidants, skin angiogenesis, anti-apoptotic activity, and collagen synthesis is increased. 36 Future applications of ACF for clinical skin injury as a unique autologous dermal filler and regeneration may offer fresh perspectives on how to treat skin that has undergone photoaging.…”

“…Some publications have reported on the skin‐protective properties of oral collagen peptides; besides, in situ, injection of rhCol III may improve photoaged skin repair by encouraging ECM synthesis and delaying collagen and elastic fiber degradation. Adipocollagen fragment (ACF), a collagen scaffold rich in adipokines and capable of slowing ECM release, was also shown to have a disproportionately more significant therapeutic impact on mouse skin photoaging, the ability for antioxidants, skin angiogenesis, anti‐apoptotic activity, and collagen synthesis is increased 36 . Future applications of ACF for clinical skin injury as a unique autologous dermal filler and regeneration may offer fresh perspectives on how to treat skin that has undergone photoaging.…”