Sunday, June 1, 2025
6/1/2025
Biomimetic intervention strategies for endogenous in utero repair of Spina Bifida - ABSTRACT Neural tube defects (NTDs), including spina bifida (SB), have a devastating impact on the health and development of infants and children, with economic, social, and physical demands or hardships placed on caregivers. SB affects approximately 2,500 live births per year in the United States, with environmental and genetic factors playing a role in its etiology. By combining bioengineering and placental-derived stem cell approaches, the CuRe (Cellular Therapy for In Utero Repair of Myelomeningocele) trial has recently advanced surgical effectiveness and improved clinical outcomes. However, in utero repair requiring fetal exposure at mid- pregnancy to reduce the ongoing damage of the exposed spinal cord represents an invasive procedure. By leveraging our expertise in the synthesis of biomimetic therapeutic strategies able to induce tissue repair by inducing a regenerative cascade at the site of lesion and in the generation of genetically induced model systems, this project aims to devise less invasive, novel intervention strategies for endogenous in utero repair of SB. The overall hypothesis is that by creating a pro-regenerative environment within the amniotic cavity, it is possible to activate the cellular and molecular cascades required to reduce the severity of SB lesions. To test these hypotheses, we will i) determine the therapeutic efficacy of amniotic fluid-based cell free strategies to modulate the in utero environment and reduce the severity of SB in a clinically relevant in-house mouse model (Fbpk8 knockout mice) (Aim 1) and ii) evaluate the protective and regenerative potential of a biomimetic thermogel for in utero repair of SB lesions in mouse and rabbit models (Aim 2). The proposed research is expected to enhance our understanding with respect to the impact of biomimetic strategies inducive of regeneration on the development of neural tube tissues following genetic and mechanical disruption. The implications of these therapeutic intervention strategies are timely and critical, as stem cell-based, and bioengineering approaches are already being deployed clinically in other areas, but a minimally invasive, early in utero intervention is still needed for families and infants affected by SB.
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