posted on 2020-07-23, 19:33authored byYulia Shmidov, Yumeng Zhu, John B. Matson, Ronit Bitton
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 (i.e., 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.