Novel microgel-based scaffolds to study the effect of degradability on human dermal fibroblasts

For improved cell integration, tissue engineering scaffolds must be designed to degrade over time. Typically, the chemistry of scaffolds is modified to alter the degradation profile by using different hydrolytic or enzymatic sites within a material. It is more challenging, however, to fabricate self-assembling, injectable scaffolds that provide tunable degradation. Our laboratory has developed microgel-based scaffolds, where individual micron-sized hydrogels are crosslinked to make larger bulk scaffolds. The size of the individual microgels permits injection, and the microgels then self-assemble into a bulk structure and crosslink. We hypothesized that the microgel-based scaffolds can be used to tune degradability by mixing degradable and non-degradable microgels at various ratios within a self-assembling scaffold. Therefore, two types of microgels were fabricated, those composed of polyethylene glycol (PEG) and those composed of a PEG-lactic acid. Importantly, the microgels were similar in size and swelling and had a low polydispersity index due to their method of fabrication. Microgels were then mixed in four ratios to fabricate scaffolds and study how changes in scaffold composition altered the 3D proliferation and morphology of human dermal fibroblasts. Microgel-based scaffolds formed with 100% degradable microgels lost >60% of their mass over the 14 days of the study. Human dermal fibroblasts were mixed within the 3D scaffolds at the time of assembly and all scaffolds had cells with high viability and typical morphology. The scaffolds that had 25%-50% degradable microgels showed statistically increased proliferation of fibroblasts after 1 and 2 weeks over non-degradable scaffolds and those scaffolds with 75% or 100% degradable microgels. Overall, this work demonstrates the development and use of a tunable, self-assembled, microgel-based scaffold to investigate the effects of degradability on cellular response.