文献：Smart Hydrogel-Based DVDMS/bFGF Nanohybrids for Antibacterial Phototherapy with Multiple Damaging Sites and Accelerated Wound Healing

文献链接：https://pubs.acs.org/doi/10.1021/acsami.0c00298

作者：Bingjie Mai, Mengqi Jia, Shupei Liu, Zonghai Sheng, Min Li,Yiru Gao, Xiaobing Wang, Quanhong Liu, and Pan Wang

相关产品：PLGA 聚乳酸羟基乳酸共聚物

原文摘要：Burn infection is one of the commonest causes of death in severely burned patients.Developing multifunctional biological nanomaterials have a great significance for the comprehensive treatment of burn infection. In this paper, we developed a hydrogelbased nano-delivery system with antibacterial activity and skin regeneration function, which was used for photodynamic antimicrobial chemotherapy (PACT) in the treatment of burns. The treatment system is mainly composed of porphyrin photosensitizer DVDMS and PLGA-encapsulated bFGF nanospheres that embedded in carboxymethyl chitosan (CMCS)-sodium alginate to form CSDP hybrid hydrogel. We systematically evaluated the inherent antibacterial performance, rheological properties, fluorescence imaging and biocompatibility of the CSDP nanosystem. Under mild photo-irradiation (30 J/cm2 , 5 min), 10 μg/ml CSDP showed excellent antibacterial and antibiofilm activities, which eradicated almost 99.99% of Staphylococcus aureus and multidrug resistant (MDR) S. aureus in vitro. KEGG analysis identified multiple signaling pathways were changed in MDR S. aureus after PACT. In the burn-infection model, CSDP-PACT successfully inhibited bacteria growth and concurrently promoted wound healing. Moreover, several regenerative factors were increased and some proinflammatory factors were reduced in the burn wounds of CSDP hydrogel treatment. These results suggest that the multifunctional CSDP hydrogel is a portable, lighttriggered, anti-bacterial theranostic-platform and CSDP-PACT provides a promising strategy or the mechanically-based synergistic treatment of burn infections.

PLGA由乳酸和羟基乙酸两种单体按不同比例共聚而成，呈现出白色或类白色的颗粒状或粉末状外观。PLGA 具有生物相容性，可用于制备化合物控释微球、纳米粒等制剂，能够准确控制化合物的释放速度和时间。在组织工程方面，PLGA 支架可为细胞生长提供良好的支撑结构。

其良好的加工性能使其能通过多种成型工艺制成薄膜、纤维、微球等不同形态的产品。该文献研究开发了一种具有抗菌活性和皮肤再生功能的水凝胶基纳米递送系统，该处理体系主要由卟啉光敏剂DVDMS和PLGA封装的bFGF纳米球组成，它们嵌在羧甲基壳聚糖（CMCS）-海藻酸钠中，形成CSDP杂化水凝胶。过程如下：

图：多功能CSDP水凝胶的示意图

CSDP水凝胶的制备

首先，采用双乳状液-溶剂蒸发法制备了PLGA-bFGF纳米颗粒。配制内水相，将bFGF 溶解于其中，接着将内水相与含有 PLGA 的有机相混合，通过剧烈搅拌等操作形成初乳。随后，把初乳进一步分散于外水相，形成稳定的双乳体系。在这一过程中，溶剂逐渐蒸发，PLGA 发生固化，从而将 bFGF 有效包封于纳米颗粒内部。在EDC/NHS的催化下，通过 CS和SA搅拌反应形成CSDP水凝胶。在此过程中，加入1 ml DVDMS和PLGA-bFGF的混合溶液并包埋入凝胶中。

图：钙黄绿素AM/PI染色的NIH-3T3细胞的荧光显微镜图像

结论：在轻度光照射下，PLGA参与制备的CSDP表现出良好的抗菌和抗菌膜活性，体外根除了近99.99%的MDR。KEGG分析发现，在PACT后，MDR金黄色葡萄球菌的多种信号通路发生了改变。在模型中，CSDP-PACT成功抑制Bacteria生长，同时促进愈合。此外，在CSDP水凝胶应用中，一些再生因子增加。