(696d) Biodegradable Polymer Cross-Linker : Independent Control of Stiffness, Toughness and Degradation Rate of Hydrogel

Hydrogels are being increasingly studied for their uses in various biomedical applications including drug delivery and tissue engineering. The successful use of a hydrogel in these applications greatly relies on a refined control of the mechanical properties including stiffness and toughness and the degradation rate. However, it is still challenging to control stiffness, toughness and degradation rate of hydrogels in an independent manner due to the interdependency between hydrogel properties. We hypothesize that a biodegradable polymeric cross-linker would allow us to decouple the dependency between hydrogel properties of various hydrogel materials. This hypothesis is examined using oxidized methacrylic alginate (OMA). The OMA is synthesized by partially oxidizing alginate to generate hydrolytically labile units and conjugating methacrylic groups. OMA is used to cross-link poly(ethylene glycol) methacrylate and poly(N-hydroxymethyl acrylamide) to form three-dimensional hydrogel systems. OMA significantly improves rigidity and toughness of both hydrogels as compared with a small molecule cross-linker. OMA also controls the degradation rate of hydrogels depending on the oxidation degree, without altering initial mechanical properties of hydrogels. Protein release rate from a hydrogel and subsequent angiogenesis in vivo are thus regulated with the chemical structure of OMA. Overall, the results of this study suggests that the use of OMA as a cross-linker will enable us to implant a hydrogel in tissue subject to an external mechanical loading and attain the desired protein release profile. The OMA synthesized in this study will be, therefore, highly useful to independently control mechanical properties and degradation rate of a wide array of hydrogels.