新型氧化石墨烯凝胶生物材料在治疗感染缺损创面中的应用

Infective defect wound is one of the most common problems in orthopaedic trauma surgery even, and there is still no satisfactive treatment. Graphene oxide （GO）which made from the the redox of graphene, is a precursor of large-scale synthesis of graphene, formed by a single layer of atoms with carboxylic acid, epoxide and hydroxyl groups on the surface. It could cause physical damage on bacterial bio film with its slice of sharp edges, by extraction of phospholipids inside cell membrane undermining the integrity of the cell membrane, eventually lead to the cytoplasm outflow. The use of GO as antimicrobial comes with several advantage such as lower price, easy to get, physical mechanism of action, low environmental pollution and cytotoxicity and less likelihood to induce microbial resistance. Our preliminary work found that 3D hydrogel embedding embryonic stem cells that can maintain the normal form, function, and cell proliferation capacity in the process of its differentiation, but it have its own drawbacks, such as it is not easy to fixed on the surface of wound. To solve them, we will make a discussion on the synergistic effect of its antibacterial property on the mice model with infective defect wound on its back. This study will provide a broader space of the important scientific basis in the treatment of bone exposed, bedsore, limb necrosis, ischemic diseases such as osteonecrosis resulting from tissue defects.

创面感染及缺损是骨科甚至创伤外科最常见的难题之一，至今没有满意的治疗方法。石墨烯是一种由碳原子以sp²杂化轨道组成六角型呈蜂巢晶格的二维碳纳米材料，经氧化还原为氧化石墨烯，利用其锋利片状边缘对细菌造成物理损伤，提取细胞膜中的磷脂从而破坏细胞膜的完整性，最终会导致细胞质流出，具有良好抗菌作用，且价格便宜易获得，环境污染小、细胞毒性小和减少细菌侵蚀等优良特性，成为抗菌剂的理想材料。本课题组在前期工作中证实了自组装水凝胶是一种能够吸收大量水份而不溶解的三维聚合物网络，具有良好的生物相容性、水渗透性，可作为一种优秀的药物缓释材料和可降解的细胞移植载体。为解决此问题，探索治疗缺损创面更多的可能性，本研究拟利用氧化石墨烯纳米凝胶生物材料检测其对小鼠背部软组织感染缺损模型的作用效果，本研究极具创新意义，将为治疗软组织感染缺损、骨质外露等提供重要的科学依据。

糖尿病足溃疡(DFU)，由于持续高血糖和炎症浸润，同时缺乏必要的营养供给和缺氧，常导致组织损伤，出现异常血管生成，若合并感染金黄色葡萄球菌(金葡菌，S. aureus)后将进一步影响愈合。 为避免抗生素滥用造成耐药菌株的产生，设计一种具有独特生物机制、更有效的治疗策略刻不容缓。 在本研究中，本课题组制备了一种由氧化石墨烯和高分子聚合物支架交联而成的温敏抗菌生物材料来治疗合并金葡菌感染DFU伤口。 本生物材料可减少IL-17介导的炎症并促进细胞增殖，并通过生物信息学和实际实验，本课题组验证了miR-21-5p和PI3K/Akt信号通路是IL-17介导的炎症的主要调节因子；miR-21-5p降低了PVT1，促进皮肤的自我更新和伤口愈合能力加快。 本研究将为治疗DFU合并感染金葡菌提供新的临床策略。