(701d) Evaluation of Polyamidoamine-Based Dual-Hardening, Injectable Hydrogels for Tissue Engineering

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. Polyamidoamines, an emerging class of polymers, offer a biocompatible, biodegradable, and water-soluble option for the creation of such crosslinked networks.

We have developed a novel injectable dual-hardening hydrogel through synthesis and combination of a pNiPAAm-based thermogelling macromer and a hydrophilic and degradable polyamidoamine crosslinking macromer. Network formation through the epoxy crosslinking reaction has been shown to be rapid and facile, and the often problematic tendency of thermogelling systems to undergo significant post-formation gel syneresis was mitigated through the combination of increased hydrogel hydrophilicity and gel hardening through concomitant chemical crosslinking. Complete evaluation of the novel hydrogels with regards to formation and equilibrium swelling behavior, compressive and rheological mechanical properties, component and system cytocompatibility, and the viability of encapsulated mesenchymal stem cells will be discussed.

Such in situ dual-hardening, dimensionally stable, defect-filling, and degradable hydrogels with high gel water content are attractive substrates for tissue engineering and cellular delivery applications. In particular, the use of water-soluble and degradable polyamidoamine polyaddition-formed macromers offers tremendous synthetic flexibility and control over subsequent gel properties. With the ability to tune hydrogel hydrophilicity, degree of post-formation swelling or syneresis, degradation timescale, degree of crosslinking, and potential introduction of additional pendant functional moieties with appropriate selection of starting comonomers, this study evaluates a promising and versatile family of injectable in situ forming hydrogels.