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

描述（由申请人提供）：本提案的总体目标是开发一种新型诱导型一氧化氮（NO）释放粘合剂水凝胶作为组织工程支持物。我们假设这些粘性水凝胶可以用作可注射的递送系统，以结合到受伤的组织部位，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递送载体以进一步帮助修复。粘合剂水凝胶由基础粘合剂PEG-纤维蛋白原水凝胶组成，其中纤维蛋白原单元衍生为诱导型一氧化氮供体。这种水凝胶是可注射的，并且可以原位展开以改善天然组织的空间和时间再生和整合。在初步实验中，粘合剂水凝胶已被合成，显示出可诱导的NO释放，并容易支持活细胞粘附。我们将追求三个目标，在这个建议中，开发和表征这些NO释放粘合剂水凝胶作为可行的可注射组织再生材料的损伤修复。目标1将 合成和表征水凝胶制剂以确定NO释放曲线、材料和粘合性能。目的2将评价这些水凝胶在体外肌腱修复模型中的作用。目的3将在临床相关的体内肌腱修复模型中评价这些水凝胶。预期的结果是，所提出的释放NO的PEG-纤维蛋白原粘附性水凝胶可用于诱导释放NO，以加速肌腱损伤部位的局部基质合成和巩固，并用作将细胞稳定递送至肌腱损伤部位的载体。 缺陷部位。该系统相对于其他类似方法的潜在优势是水凝胶固有的抗微生物和组织再生特性，以及局部递送细胞的潜力。长期目标是将这些材料作为注射疗法用于治疗急性和慢性肌腱病。

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.