(42d) Spontaneous Mineralization of Hydrophobic Hydrogels for Craniofacial Bone Tissue Regeneration

While there has been significant progress to date in the development of synthetic preformed scaffolds, many applications in tissue engineering may be better served by injectable, in situ forming and degradable hydrogel-based materials capable of delivering encapsulated cells in a non-toxic manner. In particular, thermogelling polymers, which pass through a lower critical solution temperature (LCST) upon injection into the body to spontaneously gel in situ, have shown much promise in this regard due to a near-instantaneous physical gelation mechanism. This paper reports on our recent development of a promising novel class of injectable, chemically and thermally gelling hydrophobic hydrogels capable of spontaneous mineralization in vitro and in vivo.

Poly(N-isopropylacrylamide) (PNiPAAm)-based thermogelling macromers (TGMs) with pendant functional epoxide rings and degradable polyamidoamine (PAMAM)-based crosslinking macromers were synthesized and combined to form injectable liquid solutions, which solidified within 2-3 s upon temperature elevation to 37°C and further chemically cured in under 2 h. Through this novel two-component approach, in situ forming hydrophobic hydrogels were created which addressed the often problematic tendency of thermogelling materials to undergo significant post-formation syneresis and thus demonstrated for the first time gelation of fully tunable, non-shrinking,  and cytocompatible PNiPAAm-based hydrogels which degrade by 10-12 weeks in vitro.

Furthermore, the potential of this novel class of injectable hydrogels to co-deliver mesenchymal stem cells (MSCs) in vitro through an efficient and non-toxic encapsulation was demonstrated, and the ability of such hydrophobic hydrogels to promote spontaneous mineralization was evaluated in vitro and in vivo in a rat critical-size (8 mm) cranial defect model.