Biomimetic artificial ECMs stimulate bone regeneration.

We demonstrate that a biomimetic polymer network is capable of affecting bone regeneration in vivo. Starting with a foundation consisting of an environmentally responsive poly(N-isopropylacrylamide-co-acrylic acid) hydrogel, we incorporated matrix metalloproteinase-13 (MMP-13) degradable crosslinkers and peptides containing integrin-binding domains (i.e., Arg-Gly-Asp) to create a biomimetic matrix designed to encourage osteoblast migration and proliferation. We independently tuned matrix stiffness and peptide concentration to generate a response surface model of osteoblast proliferation on different types of matrices. Osteoblast proliferation was significantly influenced by matrix stiffness (i.e., its complex modulus) and peptide concentration. When implanted in a rat femoral ablation model, these matrices induced bone regeneration only when protease degradable crosslinks were used to create the network. For the matrices with MMP-13 degradable crosslinkers, the bone formed had a trabecular-like structure and was distributed throughout the marrow space. Based on the correlated effects of matrix stiffness and ligand concentration, the response surface model will facilitate improvements in the regenerative capacity of these artificial extracellular matrices.