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

An Adipose-Derived Injectable Sustained-Release Collagen Scaffold of Adipokines Prepared Through a Fast Mechanical Processing Technique for Preventing Skin Photoaging in Mice.
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通过快速机械加工技术制备的脂肪源可注射持续释放脂肪因子胶原蛋白支架,用于预防小鼠皮肤光老化

DOI:
10.3389/fcell.2021.722427
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发表时间:
2021
影响因子:
5.5
通讯作者:
Gao J
Gao J
中科院分区:
生物学2区
文献类型:
--
作者:
Jin X;Zhang Y;Zhang X;Li Y;Xu M;Liu K;Ru J;Ma C;Yao Y;He Y;Gao J

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紫外线A(UVA)辐射是皮肤光老化的主要原因,与胶原蛋白降解和活性氧(ROS)表达增加有关。脂肪因子已被证明是皮肤光老化的有前途的治疗剂。然而,脂肪因子治疗通常受到体内释放持续时间短和生物不稳定性的限制。因此,需要开发一种提供脂肪因子的持续释放和增强的治疗效果的治疗。在这项研究中,我们开发了一种新的机械加工技术来提取脂肪组织来源的ECM成分,命名为“脂肪胶原片段”(ACF)。对ACF的物理特性、注射性能、胶原成分、DNA/RNA残留量和脂肪因子释放模式进行了体外鉴定。UVA照射后,用ACF或磷酸盐缓冲液处理L929细胞24 h。检测衰老相关β-半乳糖苷酶(SA-β-gal)、活性氧(ROS)和抗氧化酶的表达。然后,我们通过将ACF和磷酸盐缓冲盐水注射到光老化裸鼠的真皮中并在治疗后1周、2周和4周收集皮肤样品进行评估来评估其治疗效果。体内实验测定活性炭纤维释放脂肪因子的含量。免疫染色法检测ACF种植体胶原合成和降解情况。真皮厚度,成纤维细胞的表达,胶原蛋白的合成,活性氧水平,抗氧化酶的表达,毛细血管密度和凋亡细胞数进行了评估,通过组织学评估,免疫染色和聚合酶链反应在皮肤样本。我们证明ACF是浓缩的脂肪细胞外基质胶原片段,没有活细胞,可以通过细针注射。活性炭纤维处理组SA-β-gal、ROS表达降低,抗氧化酶表达升高。ACF经历胶原降解并促进ACF植入物中的新胶原合成。同时,活性炭纤维作为脂肪因子的缓释系统,通过持续释放脂肪因子增强血管生成、抗氧化能力、抗凋亡活性和胶原合成,对小鼠皮肤光老化具有显著更高的治疗效果。综上所述,活性炭纤维是一种富含脂肪因子的缓释细胞外基质胶原支架,可以预防UVA诱导的小鼠皮肤光老化。活性炭纤维可作为一种新的自体皮肤填料,用于皮肤再生的临床应用。
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.
DOI: 10.1021/acsnano.9b04384
发表时间: 2019-10-01
期刊: ACS NANO
影响因子: 17.1
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DOI: 10.1038/skinbio.2013.176
发表时间: 2013-07-01
期刊: The Journal of investigative dermatology
影响因子: --
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通讯作者: Gilchrest, Barbara A
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影响因子: 2.2
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