PDF(Pubmed)
Abstract：
Human skin-derived ECM aids cell functions but can trigger immune reactions; therefore it is addressed through decellularization. Acellular dermal matrices (ADMs), known for their regenerative properties, are used in tissue and organ regeneration. ADMs now play a key role in plastic and reconstructive surgery, enhancing aesthetics and reducing capsular contracture risk. Innovative decellularization with supercritical carbon dioxide preserves ECM quality for clinical use. The study investigated the cytotoxicity, biocompatibility, and anti-inflammatory properties of supercritical CO2 acellular dermal matrix (scADM) in vivo based on Sprague Dawley rat models. Initial experiments in vitro with fibroblast cells confirmed the non-toxic nature of scADM and demonstrated cell infiltration into scADMs after incubation. Subsequent tests in vitro revealed the ability of scADM to suppress inflammation induced by lipopolysaccharides (LPS) presenting by the reduction of pro-inflammatory cytokines TNF-α, IL-6, IL-1β, and MCP-1. In the in vivo model, histological assessment of implanted scADMs in 6 months revealed a decrease in inflammatory cells, confirmed further by the biomarkers of inflammation in immunofluorescence staining. Besides, an increase in fibroblast infiltration and collagen formation was observed in histological staining, which was supported by various biomarkers of fibroblasts. Moreover, the study demonstrated vascularization and macrophage polarization, depicting increased endothelial cell formation. Alteration of matrix metalloproteinases (MMPs) was analyzed by RT-PCR, indicating the reduction of MMP2, MMP3, and MMP9 levels over time. Simultaneously, an increase in collagen deposition of collagen I and collagen III was observed, verified in immunofluorescent staining, RT-PCR, and western blotting. Overall, the findings suggested that scADMs offer significant benefits in improving outcomes in implant-based procedures as well as soft tissue substitution.
摘要：
人皮肤来源的ECM有助于细胞功能，但可以触发免疫反应；因此，它可以通过脱细胞化来解决。脱细胞真皮基质(ADMs),以其再生特性而闻名，用于组织和器官再生。ADM现在在整形和重建手术中起着关键作用，增强美学和降低包膜挛缩的风险。用超临界二氧化碳进行创新的去细胞化保留了临床使用的ECM质量。这项研究调查了细胞毒性，生物相容性，基于SpragueDawley大鼠模型的超临界CO2脱细胞真皮基质（scADM）的体内抗炎特性。使用成纤维细胞的体外初始实验证实了scADM的无毒性质,并证明了孵育后细胞浸润到scADM中。随后的体外试验揭示了scADM通过减少促炎细胞因子TNF-α抑制脂多糖（LPS）诱导的炎症的能力，IL-6，IL-1β，和MCP-1。在体内模型中,6个月内植入scADMs的组织学评估显示炎症细胞减少，免疫荧光染色中炎症的生物标志物进一步证实。此外,在组织学染色中观察到成纤维细胞浸润和胶原蛋白形成的增加，这得到了成纤维细胞的各种生物标志物的支持。此外，这项研究证明了血管化和巨噬细胞极化，描绘内皮细胞形成增加。通过RT-PCR分析基质金属蛋白酶（MMPs）的变化，表明MMP2、MMP3和MMP9水平随时间降低。同时,观察到胶原蛋白I和胶原蛋白III的胶原蛋白沉积增加，在免疫荧光染色中验证，RT-PCR,和西方印迹。总的来说,研究结果表明,scADMs在改善基于植入物的手术和软组织替代的结局方面具有显著的优势.
