Injury to the skin from severe burns can cause debilitating physical and psychosocial distress to the patients. Upon healing, deep dermal burns often result in devastating hypertrophic scar formation. For many decades, stem cell-based therapies have shown significant potential in improving wound healing. However, current cell delivery methods are often insufficient to maintain cell viability in a harmful burn wound environment to promote skin regeneration. In this study, we developed an enhanced approach to deliver adipose-derived stem cells (ASCs) for the treatment of burn wounds, using an in-situ-formed hydrogel system comprised of a hyperbranched poly(ethylene glycol) diacrylate (HB-PEGDA) polymer, a commercially available thiol-functionalized hyaluronic acid (HA-SH) and a short RGD peptide. Stable hydrogels with tunable swelling and mechanical properties form within five minutes under physiological conditions via the Michael-type addition reaction. Combining with RGD peptide, as a cell adhesion motif, significantly alters the cellular morphology, enhances cell proliferation, and increases the paracrine activity of angiogenesis and tissue remodeling growth factors and cytokines. Bioluminescence imaging of luciferase+ ASCs indicated that the hydrogel protected the implanted cells from the harmful wound environment in burns. Hydrogel-ASC treatment significantly enhanced neovascularization, accelerated wound closure and reduced the scar formation. Our findings suggest that PEG-HA-RGD-based hydrogel provides an effective niche capable of augmenting the regenerative potential of ASCs and promoting burn wound healing. STATEMENT OF SIGNIFICANCE: Burn injury is one of the most devastating injures, and patients suffer from many complications and post-burn scar formation despite modern therapies. Here, we designed a conformable hydrogel-based stem cell delivery platform that allows rapid in-situ gelation upon contact with wounds. Adipose-derived stem cells were encapsulated into a PEG-HA-RGD hydrogels. Introducing of RGD motif significantly improved the cellular morphology, proliferation, and secretion of angiogenesis and remodeling cytokines. A deep second-degree burn murine model was utilized to evaluate in-vivo cell retention and therapeutic effect of the hydrogel-ASC-based therapy on burn wound healing. Our hydrogel remarkably improved ASCs viability in burn wounds and the hydrogel-ASC treatment enhanced the neovascularization, promoted wound closure, and reduced scar formation.

中文翻译：

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适形的透明质酸水凝胶可提供脂肪来源的干细胞并促进烧伤的再生。

严重灼伤对皮肤造成的伤害可能会使患者的身体和心理承受痛苦。愈合后，深层皮肤灼伤通常会导致破坏性肥厚性瘢痕形成。数十年来，基于干细胞的疗法在改善伤口愈合方面已显示出巨大潜力。然而，当前的细胞递送方法通常不足以在有害的烧伤创面环境中维持细胞活力以促进皮肤再生。在这项研究中，我们开发了一种增强的方法，可使用原位形成的水凝胶系统（包括超支化的聚（乙二醇）二丙烯酸酯（HB-PEGDA））来提供脂肪来源的干细胞（ASC），用于治疗烧伤创面。聚合物，市售的巯基官能化透明质酸（HA-SH）和短RGD肽。在生理条件下，通过迈克尔型加成反应，可在五分钟内形成具有可调溶胀和机械性能的稳定水凝胶。与RGD肽结合，作为细胞粘附基序，可显着改变细胞形态，增强细胞增殖，并增加血管生成和组织重塑生长因子及细胞因子的旁分泌活性。荧光素酶+ ASC的生物发光成像表明，水凝胶可保护植入的细胞免受灼伤中有害的伤口环境的伤害。水凝胶-ASC治疗显着增强了新血管形成，加速了伤口闭合并减少了疤痕的形成。我们的发现表明，基于PEG-HA-RGD的水凝胶提供了一种有效的利基市场，能够增加ASC的再生潜力并促进烧伤创面愈合。重大意义声明：烧伤是最严重的伤害之一，尽管采用现代疗法，患者仍会遭受许多并发症和烧伤后疤痕形成的困扰。在这里，我们设计了一个合适的基于水凝胶的干细胞递送平台，该平台可在与伤口接触后迅速进行原位凝胶化。将脂肪来源的干细胞封装到PEG-HA-RGD水凝胶中。引入RGD基序可显着改善细胞形态，增殖以及血管生成和重塑细胞因子的分泌。利用深层二级烧伤小鼠模型评估体内细胞保留和基于水凝胶-ASC的疗法对烧伤伤口愈合的治疗效果。我们的水凝胶可显着改善烧伤创面中的ASC活力，而水凝胶-ASC治疗可增强新血管形成，促进伤口闭合，