In tissue engineering, cells are often encapsulated in a synthetic matrix designed to degrade over time as the cells produce their own extracellular matrix (ECM), which provides structural and biochemical support of surrounding cells. The key point of designing a synthetic matrix is how to better control the degradation time of the matrix, since fast degradation may not provide sufficient time for cells to produce enough natural ECM to support themselves, while slow degradation may inhibit cell migration, ECM deposition, or other natural cellular processes. In this case, the design of synthetic matrix has gained a lot of interest, and one heavily studied type of synthetic ECM materials is polymer hydrogels. Over the past decade, many types of synthetic hydrogels have been designed to mimic the degradability and dynamics of native ECM. Here we reported how hydrogel network topology can affect degradation kinetics.<br/><br/>Despite the widespread use of hydrogels in biomedical applications, little is known regarding the effect of crosslinker topology on hydrogel degradation. Dendritic and linear elastin-like peptides (ELPs) were used as crosslinkers for hyaluronic acid (HA) hydrogels, and their enzymatic degradation was studied using trypsin. Rheological studies revealed that hydrogels crosslinked with ELP dendrimers (HA_denELPs) degraded more slowly than those crosslinked with the otherwise equivalent linear ELPs (ie, both molecules have the same number of pentamers and peripheral lysine residues). The origin of this phenomenon was evaluated using solution studies in which various dendritic and linear ELPs were treated with trypsin. Apart from the expected steric hindrances due to the dendritic topology, we identified the dual directionality of the peptide sequences (generated by a central branching lysine residue) and the likelihood of cleaving a productive crosslinking point as two additional contributors to the lesser degradability of HA_denELPs. Overall, these results highlight how the molecular design of crosslinker topology represents a novel strategy to tune the degradation rate of hydrogels.

Effect of crosslinker topology on enzymatic degradation of hydrogels

ACS Spring Meeting 2021

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