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Description
"Introduction: Minimally-invasive prenatal interventions which aim to ameliorate fetal developmental defects have become a clinical reality and are currently performed for a variety of life-threatening complications. However, in up to 30% of the cases, the intervention translates into preterm birth and its associated negative consequences. The puncture created in the fetal membranes (FMs) during fetoscopy and their reported inability to heal might play a role in the risk for iPPROM. Despite promising, none of the investigated approaches has been clinically translated, and there is currently no clinical strategy to prevent iPPROM after a fetoscopic intervention. We have earlier shown that regeneration-inducing factors, such as platelet derived growth factor (PDGF)-BB can promote the migration and proliferation of FM cells when encapsulated in a biomaterial. Here, to elucidate the potential such biomaterial for FM repair in a clinically relevant setting, we investigated the healing-triggering capacity of such biomaterial in an ovine model.
Methods: To investigate the effect of PDGF-BB to elicit a healing response of FMs, we established a FM defect model in pregnant sheep. In this novel in vivo model, we applied an umbrella-shaped nitinol implant loaded with our previously engineered poly(ethylene glycol) (TG-PEG) biomaterial that released PDGF-BB. At explantation, we performed macroscopic examinations as well as immunohistochemistry analysis of the implants.
Results: The comparison of empty or growth factor-loaded implants shows that platelet-derived growth factor (PDGF-BB) promoted a healing response consisting of angiogenesis, immune cells, and migration, proliferation and ECM deposition in the implanted biomaterial.
Conclusion: This study is a first proof-of-concept that TG-PEG hydrogels loaded with PDGF-BB, by triggering cell recruitment and proliferation from the myometrium and the vicinity of the FMs, might be able to heal FM defects. Longitudinal studies lasting until the time of delivery will be required to understand the long term healing response of the FMs."
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