(74h) A Novel Epoxy-Based, Injectable Hydrogel Scaffold for Tissue Regeneration

     While the majority of effort in tissue regeneration research has been focused on implantable scaffolds, there are many applications that would be better served with injectable, in situ forming materials capable of co-delivering cells and growth factors to optimize tissue regeneration.  Injectable scaffolds are minimally invasive and can easily fill complex tissue defects or voids often found in applications such as craniofacial bone regeneration after trauma, tumor resection, or birth defects.  Thermogelling polymers, such as poly(N-isopropylacrylamide), which pass through a lower critical solution temperature upon injection into the body, are promising candidates as scaffold backbones.  Concomitant chemical crosslinking during thermogellation further enhances the stability and mechanical properties of such materials; however these networks must be made biodegradable on an appropriate timescale for tissue regeneration.  This is a major issue for injectable materials, since many commonly used biodegradable polymers, such as polycaprolactone and poly(lactic acid), are not water soluble.  Polyamidoamines, an emerging class of polymers, offer a biocompatible, biodegradable, and water-soluble option for the creation of such crosslinked networks; and their efficacy is herein evaluated.

     To this end, a novel two-component system was developed.  Poly(NiPAAm-co-glycidyl methacrylate) was synthesized by a free radical pathway to introduce functional epoxy rings into the thermogelling polymer.  Diamine crosslinking macromers were formed from piperazine and methylene bisacrylamide with varying molecular weights through a step polymerization mechanism.  The secondary amines present at the ends of these polyamidoamine macromers reacted readily with epoxy rings, even across phases.  Thus, chemically and thermally gelling hydrogel scaffolds were formed and the effects of polymer wt %, time between solution mixing and injection, degree of crosslinking, and crosslinker length on the formation, equilibrium swelling, degradation, and mechanical properties of the scaffold were evaluated.  This system is shown to be a promising candidate for injectable tissue engineering scaffolds with little or no syneresis upon gellation and relevant degradation rates.