Regulation of tissue ingrowth into proteolytically degradable hydrogels

Regulation of the rate of cell ingrowth into and within a matrix is desirable for efficient tissue regeneration. Polyethylene glycol hydrogels crosslinked with matrix metalloproteinase (MMP) susceptible peptide sequences permit cell-controlled invasion. In this study, hydrogels of the same stiffness polymerised using different ratios of a readily degradable MMP peptide sequence (PAN-MMP) and a MMP peptide with a limited degradation capacity (MMP-9) were assessed both in vitro and in vivo for cellular invasion. The degree of invasion into the various hydrogels was found to be tightly linked to the relative proportion of each peptide both in vitro and in vivo. Furthermore a good correlation between in vitro and in vivo ingrowth was observed. These findings demonstrate a highly tunable model for regulating cellular invasion which is readily translatable to in vivo models. This finding may allow for further optimisation of aspects of regenerative scaffolds such as tissue invasion, growth factor release and cellular encapsulation. Statement of significance Degradable hydrogels are used in a wide range of tissue regeneration approaches. A particularly advantageous variant of these hydrogels is where due to peptide based crosslinking of the polymeric hydrogels, cell invasion rate is dependent on cellular enzymatic activity. This present study demonstrates a further refinement whereby both cellular and tissue invasion rates are finely regulated through the polymerisation of a hydrogel with varying combinations of enzymatically degradable peptides. Importantly this allows for invasion rates to be controlled without altering the biomechanical properties of the hydrogel such as stiffness. The latter can further influence cellular behaviour thus potentially interfering with the desired outcome.