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.
There remains an urgent clinical need for novel inducible material systems for functional tissue regeneration in instances of overuse injury. We are developing such a system that employs inducible nitric oxide releasing adhesive hydrogels that are injectable, inherently antimicrobial, and can actively support tissue regeneration.