Cranio-Maxillo-Facial Surgery Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100144, China.
Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing 100035, China.
ACS Nano. 2024 Jan 30;18(4):3553-3574. doi: 10.1021/acsnano.3c11177. Epub 2024 Jan 16.
Large full-thickness skin lesions have been one of the most challenging clinical problems in plastic surgery repair and reconstruction. To achieve in situ skin regeneration and perfect clinical outcomes, we must address two significant obstacles: angiogenesis deficiency and inflammatory dysfunction. Recently, black phosphorus has shown great promise in wound healing. However, few studies have explored the bio-effects of BP to promote in situ skin regeneration based on its nanoproperties. Here, to investigate whether black phosphorus nanosheets have positive bio-effects on in situ skin repair, we verified black phosphorus nanosheets' positive effects on angiogenic and anti-inflammatory abilities in vitro. Next, the in vivo evaluation performed on the rat large full-thickness excisional wound splinting model more comprehensively showed that the positive bio-effects of black phosphorus nanosheets are multilevel in wound healing, which can effectively enhance anti-inflammatory ability, angiogenesis, collagen deposition, and skin re-epithelialization. Then, multiomics analysis was performed to explore further the mechanism of black phosphorus nanosheets' regulation of endothelial cells in depth. Molecular mechanistically, black phosphorus nanosheets activated the JAK-STAT-OAS signaling pathway to promote cellular function and mitochondrial energy metabolism in endothelial cells. This study can provide a theoretical basis for applying two-dimensional black phosphorus nanosheets as nanomedicine to achieve in situ tissue regeneration in complex human pathological microenvironments, guiding the subsequent optimization of black phosphorus.
大面积全层皮肤损伤一直是整形外科修复和重建中最具挑战性的临床问题之一。为了实现原位皮肤再生和完美的临床效果，我们必须解决两个重大障碍：血管生成不足和炎症功能障碍。最近，黑磷在伤口愈合方面显示出巨大的潜力。然而，很少有研究基于其纳米特性探讨 BP 促进原位皮肤再生的生物效应。在这里，为了研究黑磷纳米片是否对原位皮肤修复具有积极的生物效应，我们验证了黑磷纳米片在体外对血管生成和抗炎能力的积极作用。接下来，在大鼠大面积全层切除伤夹板模型上进行的体内评价更全面地表明，黑磷纳米片在伤口愈合过程中的积极生物效应是多层次的，能有效增强抗炎能力、血管生成、胶原沉积和皮肤再上皮化。然后，进行了多组学分析，以更深入地探讨黑磷纳米片调节内皮细胞的机制。从分子机制上看，黑磷纳米片激活了 JAK-STAT-OAS 信号通路，促进了内皮细胞的细胞功能和线粒体能量代谢。这项研究为将二维黑磷纳米片作为纳米药物应用于复杂的人类病理微环境中的原位组织再生提供了理论基础，指导了黑磷的后续优化。
