3D打印纳米纤维水凝胶支架负载A-hBDs-L修复感染性缺损创面

Infectious defect wound is one of the refractory diseases for Orthopedic surgeon.Wound infection, biofilms and reduction of angiogenesis are the extremely important factors associated with chronic wound healing. As the only cathelicidin-derived antimicrobial peptide found in humans, hBDs has been widely studied for their broad spectrum of antimicrobial and angiognensis activity. Previous studies have shown that replacing the N-terminal and C-terminal in antimicrobial peptide in order with two caps, APKAM and LQKKGI, to become a new cathelicidin-derived antimicrobial peptide. It could be reduced cytotoxicity, enhanced its stability, and improved the antibacterial activity in the environment of high permeability. Our preliminary work found that hydrogel embedding cells and embryonic cytokine can maintain their activity, but it has some drawbacks, such as uneven distribution, not easy to fixed on the surface of wound. In order to solve the disadvantage, this study will design a novel kind of nano fiber hydrogel scaffold encapsulating the A-hBDs-L with computer, make it with the latest and rised-up method, the 3D printing technology, which could accurate control of the ratio of matrix/alginate and the distribution of A-hBDs-L.The compound nano fiber hydrogel scaffold will be monitored in the treatment of chronic wound models on rats’ back. We will make a discussion on the synergistic effect of its antibacterial property and ability of stimulating angiogenesis. This study will provide a broader space of the important scientific basis in the treatment of infectious defect wound.

感染性缺损创面是创伤骨科医生面临的难治性疾病之一。感染、细菌生物膜形成及血管生成减少等是导致创面难以愈合的重要因素。近年来，人源性β防御素（hBDs）因其具有抗感染、促血管化等多种生物学活性被广泛关注。研究表明，在抗菌肽的N端和C端分别置换APKAM和LQKKGI这两个氨基酸残基帽后，不仅可以降低其细胞毒性，增强结构稳定性，还能提高其抗菌活性。本课题组前期研究发现，三维水凝胶包埋细胞及细胞因子后，能长期维持细胞及细胞因子的活性，促进创面修复。但细胞及细胞因子在水凝胶内时空分布不均，且单纯水凝胶流动性强不易固定于创面表面，导致治疗效果不佳。为解决此问题，本研究拟利用3D打印技术，精确控制基质胶/藻朊酸盐的比例及A-hBDs-L的时空均匀分布，构建个体化纳米纤维水凝胶支架，检测其对小鼠背部软组织感染性缺损创面的疗效。本研究极具创新意义，将为治疗软组织感染性缺损创面提供重要的科学依据。

感染性缺损创面是创伤骨科医生面临的难治性疾病之一。感染、细菌生物膜形成及血管生成减少等是导致创面难以愈合的重要因素。近年来，人源性β防御素（hBDs）因其具有抗感染、促血管化等多种生物学活性被广泛关注。前期研究表明，在抗菌肽的N端和C端分别置换APKAM和LQKKGI这两个氨基酸残基帽后，不仅可以降低其细胞毒性，增强结构稳定性，还能提高其抗菌活性。我们前期研究发现，三维水凝胶包埋细胞及细胞因子后，能长期维持细胞及细胞因子的活性，促进创面修复。但细胞及细胞因子在水凝胶内时空分布不均，且单纯水凝胶流动性强不易固定于创面表面，导致治疗效果不佳。为解决此问题，本课题组利用3D打印技术，精确控制基质胶/藻朊酸盐的比例及A-hBDs-L的时空均匀分布，构建个体化纳米纤维水凝胶支架，经过基础研究和动物实验证实，新合成的3D打印水凝胶能显著促进小鼠背部软组织感染性缺损创面愈合并清楚阐释具体机制，关键数据详见已发表学术论文成果。本研究极具创新意义，将为临床治疗软组织感染性缺损创面提供新的科学依据和手段。