Development of an Injectable Nitric Oxide Releasing Poly(ethylene) Glycol-Fibrin Adhesive Hydrogel

Abstract

Fibrin microparticles were incorporated into poly(ethylene) glycol (PEG)-fibrinogen hydrogels to create an injectable, composite that could serve as a wound healing support and vehicle to deliver therapeutic factors for tissue engineering. Nitric oxide (NO), a therapeutic agent in wound healing, was loaded into fibrin microparticles by blending S-Nitroso-N-acetyl penicillamine (SNAP) with a fibrinogen solution. The incorporation of microparticles affected swelling behavior and improved tissue adhesivity of composite hydrogels. Controlled NO release was induced via photolytic and thermal activation, and modulated by weight percent of particles incorporated. These NO-releasing composites were non-cytotoxic in culture. Cells maintained morphology, viability, and proliferative character. Fibrin microparticles loaded with SNAP and incorporated into a PEG-fibrinogen matrix, creates a novel injectable composite hydrogel that offers improved tissue adhesivity and inducible NO-release for use as a regenerative support for wound healing and tissue engineering applications.

Specialty Tough Hydrogels and Their Biomedical Applications

“…[163] The with strong adhesive properties towards clinical applications. [164] Interpenetrating Network Adhesives Mooney's group developed a bilayered tough adhesive: (i) an interpenetrating, charged polymer adhesive and (ii) a dissipative matrix (e.g. Alg-PAAm).…”

Application of Composite Hydrogels to Control Physical Properties in Tissue Engineering and Regenerative Medicine

“…Composite hydrogels provide a possible solution to aid in the acceleration of wound repair in tendons via tissue-engineering scaffolds that passively or actively promote regeneration. One recent example of incorporating composite hydrogels in tendinopathy is the use of microparticulate-reinforcing phases in polyethylene glycol (PEG)-fibrinogen adhesive-hydrogels [29,63]. Hydrogels that integrate PEG into their structures are suitable for tissue-regeneration matrices because they are inherently biocompatible, easily cross-linked, and have the potential for tailored mechanical properties and performance as controlled drug-delivery vehicles (i.e., growth factors and other active molecules) [64].…”

“…Hierarchical classification of composite hydrogels based on their reinforcing phases at micro and nanoscales. ( A ) Reinforcement shape may be particulate, fibrous, or a hybridization of the two [24,25,26,27,28]; ( B ) both particulate and fibrous reinforcement has either uniform or random orientations [29]; ( C ) fibers in a reinforcing phase can be classified as long or short and further organized based upon fiber diameters or thicknesses; ( D ) within a composite, fibers may have continuous or discontinuous patterns [8]. …”

New Developments in Medical Applications of Hybrid Hydrogels Containing Natural Polymers

“…Such combinations can be resulted by polymerization or conjugation (click chemistry) with synthetic polymers resulting compatible hybrid hydrogels both in vitro and in vivo as it was demonstrated by cell differentiation, proliferation, migration studies and drug delivery, tissue engineering, wound healing applications [13,14], respectively or sequestration of growth factors from the surrounding medium [15]. Commonly, the hybrid hydrogels are heterogeneous and this property is important to assure cell adhesion, organization, and cell-cell interactions required for medical applications [16][17][18][19].…”