Adhesive PEG-fibrinogen nitric oxide releasing hydrogels for use as a wound heali

描述(申请人提供)：本提案的总体目标是开发一种新型的诱导型一氧化氮(NO)释放粘附性水凝胶作为组织工程支架。我们推测，这些粘附性水凝胶可以用作注射递送系统，结合到损伤的组织部位，并递送受控剂量的一氧化氮作为再生支持 加速伤口愈合。这些水凝胶可以进一步用作细胞输送载体，以进一步帮助修复。该粘附性水凝胶由具有衍生成诱导性一氧化氮供体的纤维蛋白原单元的基本粘附性聚乙二醇-纤维蛋白原水凝胶组成。这种水凝胶是可注射的，可以在原位展开，以改善自然组织的时空再生和整合。在初步实验中，已经合成了粘附性水凝胶，显示出可诱导的NO释放，并容易支持活细胞黏附。在这项提案中，我们将追求三个目标，开发和表征这些不释放的粘附性水凝胶，作为可行的可注射组织再生材料，用于损伤修复。目标1将 合成和表征水凝胶配方，以确定NO释放曲线、材料和粘合性能。目的2将在体外肌腱修复模型中评估这些水凝胶的效果。AIM 3将在临床相关的体内肌腱修复模型中评估这些水凝胶。预期的结果是，所提出的释放一氧化氮的聚乙二醇纤维蛋白原粘附性水凝胶可以用于诱导释放一氧化氮，以加速肌腱损伤部位的局部基质合成和巩固，并作为一种载体，将细胞稳定地输送到 缺陷部位。与其他类似方法相比，该系统的潜在优势是水凝胶固有的抗微生物和组织再生特性，以及局部输送细胞的可能性。长期目标是将这些材料作为注射疗法应用于急慢性肌腱病的治疗。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to develop a novel inducible nitric oxide (NO) releasing adhesive hydrogel as a tissue engineering support. We hypothesize that these adhesive hydrogels could be used as injectable delivery systems to bind to an injured tissue site and deliver controlled doses of nitric oxide as a regenerative support to accelerate wound healing. These hydrogels could further be used as cell delivery vehicle to further aid in repair. The adhesive hydrogel is composed of a base adhesive PEG-fibrinogen hydrogel with the fibrinogen unit derivatized into an inducible nitric oxide donor. This hydrogel i injectable and can be deployable in-situ to improve the spatial and temporal regeneration and integration of native tissue. In preliminary experiments the adhesive hydrogel has been synthesized, shown to exhibit inducible NO release, and readily support viable cell adhesion. We will pursue three aims in this proposal to develop and characterize these NO-releasing adhesive hydrogels as viable injectable tissue regenerative materials for injury repair. Aim 1 will synthesize and characterize hydrogel formulations to determine NO-releasing profiles, materials and adhesive properties. Aim 2 will evaluate the effect of these hydrogels in an in vitro tendon repair model. Aim 3 will evaluate these hydrogels in a clinically relevant in vivo tendon repair model. The expected outcome is that the proposed NO-releasing PEG-fibrinogen adhesive hydrogel can be used to inducibly release NO to accelerate local matrix synthesis and consolidation at a tendon injury site and to act as a vehicle for the stable delivery of cells to a defect site. The potential advantage of this system over other similar approaches is the inherent antimicrobial and tissue regenerative character of the hydrogel coupled with the potential for localized delivery of cells. A long-term goal is to apply these materials as injectable therapies fr the treatment of acute and chronic tendinopathy.