Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Research Unit of Peptide Science, Chinese Academy of Medical Sciences 2019RU066, Lanzhou University, West Donggang Road 199, Lanzhou 730000, PR China; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou 730000, PR China.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Research Unit of Peptide Science, Chinese Academy of Medical Sciences 2019RU066, Lanzhou University, West Donggang Road 199, Lanzhou 730000, PR China.
Acta Biomater. 2022 Oct 1;151:223-234. doi: 10.1016/j.actbio.2022.07.066. Epub 2022 Aug 7.
Bacterial infection and local growth factor deficiency are two of the major causes of the nonunion of diabetic wounds. Antimicrobial peptides (AMPs) are believed to be alternatives to antibiotics against drug-resistant bacterial infections. 8-Bromoadenosine-3', 5'-cyclic monophosphate (8Br-cAMP) can promote cells to secrete growth factors and accelerate cell proliferation. In the present study, we constructed a hydrogel with antimicrobial peptide Jelleine-1 (J-1) and 8Br-cAMP without any other gelators or chemical crosslinking agents. The hydrogel was proved to promote the secretion of transforming growth factor-β (TGF-β) and vascular endothelial growth factor-A (VEGFA) in vitro and in vivo. Notably, it exhibited potent potential for wound healing in methicillin-resistant Staphylococcus aureus (MRSA) infected diabetic wounds. This would be attributed to the retention of AMPs and 8Br-cAMP on the wound site by the hydrogel system. In addition, the hydrogel also showed good biodegradability, proper stability, and good biocompatibility. This study would shed light on the development of carrier-free and multifunctional hydrogel for wound healing. STATEMENT OF SIGNIFICANCE: Bacterial infection and local growth factor deficiency are two of the major causes for the nonunion of refractory wounds. In the present study, an injectable carrier-free hydrogel was constructed of a natural antimicrobial peptide J-1 and 8Br-cAMP by eco-friendly physical crosslinking without any other gelators or chemical crosslinking agents. The hydrogel exhibited excellent antimicrobial activity and was proved to promote the secretion of TGF-β and VEGFA in vitro and in vivo. Correspondingly, the hydrogel showed exceptionally wound healing effects in the wound model of MRSA infected diabetic rats. This study would provide an alternative strategy or a potential hydrogel dressing for the treatment of chronic or refractory wounds.
细菌感染和局部生长因子缺乏是糖尿病创面不愈合的两个主要原因。抗菌肽（AMPs）被认为是对抗耐药菌感染的抗生素替代品。8-溴腺苷-3'，5'-环单磷酸（8Br-cAMP）可以促进细胞分泌生长因子并加速细胞增殖。在本研究中，我们构建了一种含有抗菌肽 Jelleine-1（J-1）和 8Br-cAMP 的水凝胶，而无需任何其他凝胶剂或化学交联剂。该水凝胶被证明可以在体外和体内促进转化生长因子-β（TGF-β）和血管内皮生长因子-A（VEGFA）的分泌。值得注意的是，它在耐甲氧西林金黄色葡萄球菌（MRSA）感染的糖尿病创面中表现出很强的愈合潜力。这归因于水凝胶系统在创面部位保留 AMPs 和 8Br-cAMP。此外，该水凝胶还表现出良好的生物降解性、适当的稳定性和良好的生物相容性。本研究将为开发无载体多功能水凝胶用于创面愈合提供思路。
细菌感染和局部生长因子缺乏是难治性创面不愈合的两个主要原因。在本研究中，构建了一种由天然抗菌肽 J-1 和 8Br-cAMP 通过环保的物理交联制成的无载体水凝胶，无需任何其他凝胶剂或化学交联剂。该水凝胶表现出优异的抗菌活性，并被证明可以在体外和体内促进 TGF-β 和 VEGFA 的分泌。相应地，该水凝胶在 MRSA 感染的糖尿病大鼠创面模型中表现出出色的创面愈合效果。本研究为治疗慢性或难治性创面提供了一种替代策略或潜在的水凝胶敷料。
