(275f) Optimization of Thermogelling, Injectable Scaffolds for Craniofacial Tissue Regeneration

     The development of a suitable replacement for autogenous bone grafts in the treatment of craniofacial bone defects resulting from trauma, deformities, degenerative diseases, and tumor resection is a major scientific goal.  An injectable, in situ forming synthetic scaffold capable of co-delivering cells and growth factors to enhance tissue regeneration would enable a non-invasive procedure capable of filling complex bone defects with no donor-site morbidity.  A promising approach is to utilize organic, thermogelling polymers, such as poly(N-isopropylacrylamide, which pass through a lower critical solution temperature (LCST) upon injection into the body.  Simultaneous chemical crosslinking of the polymer matrix has been used to enhance the mechanical properties of the formed gels and reduce syneresis.  This material must also be made biocompatible and biodegradable with non-toxic and soluble degradation products. 

     In this paper, a recently developed system is presented that is capable of eliminating the commonly encountered problem of significant syneresis as a result of the thermogellation mechanism.  Modest incorporation of 3-sulfopropyl acrylate potassium salt into poly(NiPAAm-co-acrylamide-co-2-hydroxyethyl acrylate) progressively increased the equilibrium degree of swelling to create non-shrinking, injectable scaffolds.  Additionally, a novel method to produce soluble degradation products from a thermogelling scaffold is presented.  By modifying the base polymer with methacryloyl chloride to introduce crosslinkable moieties, the LCST of the polymer was reduced below body temperature.  After injection and crosslinking through free radical pathways, the hydrolytic degradation of the scaffold resulted in soluble polymer chains.  Thus, a promising system for injectable tissue engineering scaffolds has been developed through improvement and optimization of previous research efforts with similar polymers.