In situ sprayed NIR-responsive, analgesic black phosphorus-based gel for diabetic ulcer treatment

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 46; pp. 28667 - 28677
• Main Authors: Ouyang, Jiang, Ji, Xiaoyuan, Zhang, Xingcai, Feng, Chan, Tang, Zhongmin, Kong, Na, Xie, Angel, Wang, Junqing, Sui, Xinbing, Deng, Liu, Liu, Younian, Kim, Jong Seung, Cao, Yihai, Tao, Wei
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17.11.2020
• Subjects: Anesthetics, Local - administration & dosage; Angiogenesis; Animals; Bacterial diseases; Biological Sciences; Biomimetics; Blood flow; Cell Line; Cell proliferation; Cell Proliferation - drug effects; Chronic infection; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental; Diabetic Foot - therapy; Drug Evaluation, Preclinical; Endothelial cells; Endothelial Cells - drug effects; Fibrinogen - administration & dosage; Gels; Human Umbilical Vein Endothelial Cells; Humans; Irradiation; Lidocaine; Lidocaine - administration & dosage; Male; Medicin och hälsovetenskap; Mice, Inbred BALB C; Near infrared radiation; Neovascularization, Physiologic - drug effects; Pain; Phosphorus; Phosphorus - administration & dosage; Photothermal Therapy; Physical Sciences; Smart Materials - administration & dosage; Thrombin - administration & dosage; Ulcers; Vascularization; Wound healing; Wound Healing - drug effects; wound healing; diabetic ulcer; black phosphorus; analgesic; fibrin gel
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2016268117

The treatment of diabetic ulcer (DU) remains a major clinical challenge due to the complex wound-healing milieu that features chronic wounds, impaired angiogenesis, persistent pain, bacterial infection, and exacerbated inflammation. A strategy that effectively targets all these issues has proven elusive. Herein, we use a smart black phosphorus (BP)-based gel with the characteristics of rapid formation and near-infrared light (NIR) responsiveness to address these problems. The in situ sprayed BP-based gel could act as 1) a temporary, biomimetic “skin” to temporarily shield the tissue from the external environment and accelerate chronic wound healing by promoting the proliferation of endothelial cells, vascularization, and angiogenesis and 2) a drug “reservoir” to store therapeutic BP and pain-relieving lidocaine hydrochloride (Lid). Within several minutes of NIR laser irradiation, the BP-based gel generates local heat to accelerate microcirculatory blood flow, mediate the release of loaded Lid for “on-demand” pain relief, eliminate bacteria, and reduce inflammation. Therefore, our study not only introduces a concept of in situ sprayed, NIR-responsive pain relief gel targeting the challengingwound-healing milieu in diabetes but also provides a proof-of-concept application of BP-based materials in DU treatment.