智能细菌纤维素调控胶原分布及创伤修复的机制研究

Wound repair has recently become a hot topic in the orthopedic surgery in China as there is a boost of the numer of people who are wounded in natural disasters, transportation accidents and chronic degenerate diseases (diabetes), as well as, a strong demand for orthopedic surgery. Current studies on wound repair have standed on the molecular/genetic level. However, due to stability, biosafety and cost, cures on the molecular/genetic level are not popularly accepted. Wound healing is a complicatedly biological process which includes four phases, inflammation, cell migration and proliferation, angiogenesis and epithelialization, and tissue remolding. One has revealed that, although wound healing is too complex to understand, collagen playes a very important role during would healing. The orderly parallel distribution of collagen only appears in the worse wound healing with ugly scar tissue, while randomly reticular distribution of collagen appears in the excellent wound healing following less or no scar tissue. At present, most of wound repairs are focused on regulating growth factors or ECM molecules to promote wound healing. Wound repair materials are also based on this perspective to provide a single fuction either promoting cell attachment or stimulating some growth factors during wound healing. As mentioned,collagen is a vital protein in the middle and late phases of wound healing. However, it is interesting that the relationship between the distribution of collagen and wound healing/scar information has never been studied. In this proposal, therefore, we hypothesize that the distribution of collagen on the wound are direct reasons which bring about wound healing towards scar-free tissue regeneration. From the point of a biomaterial scientist, we use surface micropattern to modify a biomaterial with good biocompatibility - bacterial cellulose, which render bacterial cellulose the ability of guiding collagen during wound healing. This smart bacterial cellulose is used as a substrate to explore the relationship between the distribution of collagen on the wound and wound healing/scar formation. Following this hypothesis, we expect to preliminarily explore a novel perspective of wound repair and derive a novel multifunctional material, which can promote the attachment/migration of cell and guide the deposition /distribute of collagen, to drive wound towards excellent healing and scar-free tissue regeneration.

利用分子水平调控进行创伤修复研究已逐渐成为21世纪中国外科领域研究热点。创伤修复是一个复杂的生物学过程，由生长因子诱导的细胞迁移增殖及胶原纤维在伤口部位的沉积与分布是创伤愈合的关键因素。本课题基于此观点，另辟蹊径，设想以具有胶原诱导功能的智能细菌纤维素材料来替代生长因子诱导胶原沉积与分布，用以揭示创伤修复中胶原沉积分布与创伤愈合、瘢痕形成之间的关系，从而探寻一条创伤修复的新思路。本课题首先从材料入手，对具有良好生物相容性的细菌纤维素材料进行表面微图形化改性，以赋予其可诱导胶原分布的功能。以体外模拟细胞培养实验来初步检验智能细菌纤维素诱导胶原分布的功能性。在不需要昂贵的分子水平治疗介入情况下，这种以智能材料来替代生长因子调控的创伤修复方法期望仍然能够有效诱导胶原在伤口部位沉积与分布，并能改善创伤愈合和减少瘢痕形成。

创伤愈合是一个复杂的生理过程，而在创伤修复中后期胶原的形成与胶原蛋白分布对伤口愈合和瘢痕是否形成有着密切的关系。本项目通过研究胶原与瘢痕形成之间的关系，来调控创伤愈合过程中胶原的分布和排列，达到促进无瘢痕伤口愈合的目的。本项目以具有良好生物相容性的细菌纤维素（BC）为基材，采用低功率CO2激光器在其表面构造一定的微图形，同时利用小分子生物活性肽RGDS短肽对图形部分进行修饰，研究人皮肤呈纤维素（HSF）细胞在修饰后的微图形化BC材料表面的分布情况。实验结果表明小功率CO2激光器能够在BC表面构造精确、均匀的微图形，并且微图形在材料吸水后保持良好；经RGDS修饰后，BC的生物活性明显提高，有利于HSF细胞粘附和增殖；经DAPI荧光染色后荧光显微镜观察发现，HSF细胞主要分布在微图形的凸台表面，扫描电镜在图形的沟槽中也没有发现HSF细胞存在。这与本项目预期的设想相符，说明RGDS修饰后的微图形化的BC引导了HSF细胞的分布，而细胞的这种分布将会导致其分泌的胶原的排布发生一定的变化，而这将会对创伤修复后期疤痕组织的形成造成一定的影响，具体影响需要更进一步地试验来研究探讨。