(499b) Injectable, In Situ Hardening Macromers for Bone Tissue Engineering

Injectable biomaterials are desirable in tissue engineering for many reasons, including the ability to fill defects of complex shapes through minimally invasive delivery methods and to deliver cells and growth factors during injection. Many injectable biomaterials are hydrogels, a class of crosslinked hydrophilic polymers characterized by a high water content, making them ideal carriers for encapsulated cells and growth factors. In bone tissue engineering applications the need for injectable or moldable materials is great as the surgical protocols prior to placement of an implant often call for extensive debridement, making scaffold prefabrication difficult or impossible. Hydrogels are often not ideal as they lack the mechanical strength necessary to fill and stabilize a bony defect.

In order to address this weakness, we have synthesized novel biodegradable macromers containing hydrophobic moieties as well as moieties promoting ionic crosslinking and subsequent hardening in situ. These materials were synthesized via radical polymerization from pentaerythritol diacrylate monostearate, a hydrophobic building block to mediate disperse interaction and mechanical stability, vinyl phosphonic acid, a calcium-binding moiety, and other acrylic monomers including N-isopropylacrylamide. The chemical structure of the macromers was verified using NMR spectroscopy and thermogravimetric analysis. Rheology was used to determine gelation properties and mechanical characteristics of the macromers in regular culture media as well as in the presence of high Ca++ solution. Dynamic light scattering was also used to investigate the interaction of these macromers with free calcium ions. Cytocompatibility of the macromers was also investigated.

Initial results demonstrate that we have synthesized macromers containing the radically polymerized monomers in ratios close to those of the monomer feeds. The materials are liquid at room temperature but undergo a rapid sol-gel transition at around 37ºC, making them a suitable candidate as injectable biomaterials. Rheological studies further indicate that in the presence of free calcium ions, this rapid temperature-dependent phase transition occurs at a lower temperature and that the resultant gel has a higher storage modulus than gels formed in the absence of free calcium ions. Direct contact cytocompatibility assays demonstrate that these materials have good cytocompatibility when compared to positive controls (tissue culture polystyrene).

In summary, we have synthesized novel, cytocompatible macromers that undergo a rapid sol-gel transition at temperatures close to body temperature and also interact with free calcium ions to further stabilize the gel. These materials warrant further investigation as matrices for cell delivery and bone tissue engineering applications.