• Methacrylic alginate;
  • Neovascularization;
  • Poly(ethylene glycol);
  • Protein release


Hydrogels are being increasingly studied for use 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, toughness, and the degradation rate. However, it is still challenging to control the hydrogel properties in an independent manner due to the interdependency between hydrogel properties. Here it is hypothesized that a biodegradable polymeric crosslinker would allow for decoupling of the dependency between the 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. It is used to crosslink 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 crosslinker, and also controls the degradation rate of hydrogels depending on the oxidation degree, without altering their initial mechanical properties. The 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 crosslinker will allow the implantation of a hydrogel in tissue subject to an external mechanical loading with a desired protein-release profile. The OMA synthesized in this study will be, therefore, highly useful to independently control the mechanical properties and degradation rate of a wide array of hydrogels.