Slow-healing and chronic wounds represent a major global economic and medical burden, and there is significant unmet need for novel therapies which act to both accelerate wound closure and enhance biomechanical recovery of the skin. Here, we report a new approach in which bioactives that augment early stages of wound healing can kickstart and engender effective wound closure in healthy and diabetic, obese animals, and set the stage for subsequent tissue repair processes. We demonstrate that a nanomaterial dressing made of silk fibroin and gold nanorods (GNR) stimulates a pro-neutrophilic, innate immune, and controlled inflammatory wound transcriptomic response. Further, Silk-GNR, lasered into the wound bed, in combination with exogeneous histamine, accelerates early-stage processes in tissue repair leading to effective wound closure. Silk-GNR and histamine enhanced biomechanical recovery of skin, increased transient neoangiogenesis, myofibroblast activation, epithelial-to-mesenchymal transition (EMT) of keratinocytes and a pro-resolving neutrophilic immune response, which are hitherto unknown activities for these bioactives. Predictive and temporally coordinated delivery of growth factor nanoparticles that modulate later stages of tissue repair further accelerated wound closure in healthy and diabetic, obese animals. Our approach of kickstarting healing by delivering the “right bioactive at the right time” stimulates a multifactorial, pro-reparative response by augmenting endogenous healing and immunoregulatory mechanisms and highlights new targets to promote tissue repair.

中文翻译：

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生物活性纳米材料启动早期修复过程并增强健康和糖尿病伤口的时间调节愈合


愈合缓慢的慢性伤口是全球主要的经济和医疗负担，对既能加速伤口闭合又能增强皮肤生物力学恢复的新疗法的需求尚未得到满足。在这里，我们报告了一种新方法，其中促进伤口愈合早期阶段的生物活性剂可以在健康和糖尿病、肥胖动物中启动并产生有效的伤口闭合，并为随后的组织修复过程奠定基础。我们证明，由丝素蛋白和金纳米棒 (GNR) 制成的纳米材料敷料可刺激促中性粒细胞、先天免疫和受控的炎症伤口转录组反应。此外，Silk-GNR 与外源性组胺结合激光进入伤口床，可加速组织修复的早期过程，从而有效闭合伤口。 Silk-GNR 和组胺可增强皮肤的生物力学恢复、增加瞬时新生血管生成、肌成纤维细胞活化、角质形成细胞的上皮间质转化 (EMT) 以及促进中性粒细胞免疫反应，这些是这些生物活性物质迄今为止未知的活性。生长因子纳米颗粒的预测性和时间协调性递送可调节组织修复的后期，进一步加速健康和糖尿病、肥胖动物的伤口闭合。我们通过“在正确的时间提供正确的生物活性”来启动愈合的方法，通过增强内源性愈合和免疫调节机制来刺激多因素、促修复反应，并突出促进组织修复的新目标。