Engineered Platelet-Derived Growth Factor-Releasing Hydrogels Promote Fetal Membrane Healing In Vivo

Fetoscopic interventions to treat fetal anomalies are currently performed for a variety of conditions. Depending on the procedure, preterm rupture of the fetal membranes (FMs) happens in around 30% of the cases, potentially leading to preterm birth and fetal morbidity and mortality. Here, the capacity of modular transglutaminase crosslinked poly(ethylene glycol) (TG-PEG) hydrogels that release platelet-derived growth factor (PDGF)-BB to promote FM healing is described. In vitro, such growth factor-loaded hydrogels are able to stimulate amniotic cell migration and proliferation. When applied in vivo, these TG-PEG hydrogels tightly seal the FM and uterus defects created by a fetoscope and remain stable for 10 days. The migration of healing-related cells into such hydrogels in the myometrium, endometrium, and FM areas is only possible in soft TG-PEG hydrogels. Importantly, bioengineered hydrogels releasing PDGF-BB promote recruitment of host cells from the myometrium and the endometrium, and to a lesser extent from FM areas. In such hydrogels, the potent proliferation and matrix production of the recruited cells at the site of treatment into the biomaterial initiates a robust early healing response. PDGF-BB-loaded TG-PEG hydrogels hold great promise for the treatment of fetoscopy-induced FM defects and for the prevention of preterm birth.