1 research outputs found
Biopolymer Molecular Weight Can Modulate the Wound Healing Efficacy of Multivalent Sonic Hedgehog–Hyaluronic Acid Conjugates
There is a clinical need for new
therapeutics to improve healing
of chronic impaired wounds. Thus, we investigated how biopolymer conjugation
could be used to improve the wound healing performance of a key growth
factor for tissue regeneration: Sonic hedgehog (Shh). We generated
two multivalent Shh conjugates (mvShh) using hyaluronic acid with
two different MWs, which exhibited equivalent potency and proteolytic
protection <i>in vitro</i>. Using db/db diabetic mice, we
showed that mvShh made with smaller HyA MW resulted in more rapid
and robust neovascularization compared to mvShh made with larger MW
HyA. Further, smaller mvShh conjugates resulted in faster wound resolution
compared to the unconjugated Shh. This study is the first to show
how the wound healing efficacy of multivalent protein–polymer
conjugates is sensitive to the polymer MW, and our findings suggest
that this parameter could be used to enhance the efficacy of growth
factor conjugates