关键词: Gelatin methacrylate Platelet lysate Pressure ulcers Skin Wound healing

Mesh : Animals Humans Mice Angiogenesis / drug effects Blood Platelets / metabolism Cell Movement / drug effects Cell Survival / drug effects Fibroblasts / metabolism drug effects Gelatin / chemistry pharmacology Human Umbilical Vein Endothelial Cells Hydrogels / chemistry Methacrylates / chemistry pharmacology Neovascularization, Physiologic / drug effects Pressure Ulcer / therapy Regeneration / drug effects Skin / blood supply drug effects metabolism pathology STAT3 Transcription Factor / metabolism Wound Healing / drug effects

来  源:   DOI:10.1038/s41598-024-67304-2   PDF(Pubmed)

Abstract:
Pressure ulcers (PU) are caused by persistent long-term pressure, which compromises the integrity of the epidermis, dermis, and subcutaneous adipose tissue layer by layer, making it difficult to heal. Platelet products such as platelet lysate (PL) can promote tissue regeneration by secreting numerous growth factors based on clinical studies on skin wound healing. However, the components of PL are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel that has lately emerged as a promising material for tissue engineering and regenerative medicine. The PL liquid was extracted, flow cytometrically detected for CD41a markers, and evenly dispersed in the GelMA hydrogel to produce a surplus growth factor hydrogel system (PL@GM). The microstructure of the hydrogel system was observed under a scanning electron microscope, and its sustained release efficiency and biological safety were tested in vitro. Cell viability and migration of human dermal fibroblasts, and tube formation assays of human umbilical vein endothelial cells were applied to evaluate the ability of PL to promote wound healing and regeneration in vitro. Real-time polymerase chain reaction (PCR) and western blot analyses were performed to elucidate the skin regeneration mechanism of PL. We verified PL\'s therapeutic effectiveness and histological analysis on the PU model. PL promoted cell viability, migration, wound healing and angiogenesis in vitro. Real-time PCR and western blot indicated PL suppressed inflammation and promoted collagen I synthesis by activating STAT3. PL@GM hydrogel system demonstrated optimal biocompatibility and favorable effects on essential cells for wound healing. PL@GM also significantly stimulated PU healing, skin regeneration, and the formation of subcutaneous collagen and blood vessels. PL@GM could accelerate PU healing by promoting fibroblasts to migrate and secrete collagen and endothelial cells to vascularize. PL@GM promises to be an effective and convenient treatment modality for PU, like chronic wound treatment.
摘要:
压疮(PU)是由持续的长期压力引起的,这损害了表皮的完整性,真皮,和皮下脂肪组织逐层,很难治愈。基于对皮肤伤口愈合的临床研究,血小板产物如血小板裂解物(PL)可通过分泌多种生长因子来促进组织再生。然而,PL的成分难以保留在伤口中。甲基丙烯酸明胶(GelMA)是一种可光聚合的水凝胶,最近已成为组织工程和再生医学的有前途的材料。提取PL液体,流式细胞术检测CD41a标记物,并均匀分散在GelMA水凝胶中以产生剩余的生长因子水凝胶体系(PL@GM)。在扫描电子显微镜下观察了水凝胶体系的微观结构,并对其体外缓释效率和生物安全性进行了测试。人真皮成纤维细胞的细胞活力和迁移,应用人脐静脉内皮细胞的管形成试验来评估PL在体外促进伤口愈合和再生的能力。进行实时聚合酶链反应(PCR)和蛋白质印迹分析以阐明PL的皮肤再生机制。我们在PU模型上验证了PL的治疗效果和组织学分析。PL促进细胞活力,迁移,伤口愈合和体外血管生成。实时PCR和蛋白质印迹表明PL通过激活STAT3抑制炎症并促进胶原蛋白I合成。PL@GM水凝胶系统显示出最佳的生物相容性,并对伤口愈合的必需细胞具有良好的作用。PL@GM也显著刺激PU愈合,皮肤再生,皮下胶原蛋白和血管的形成。PL@GM可以通过促进成纤维细胞迁移并分泌胶原蛋白和内皮细胞血管化,从而加速PU的愈合。PL@GM有望成为PU的有效和方便的治疗方式,比如慢性伤口治疗.
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