) Open spina bifida or myelomeningocele (MMC) is a devastating neurologic congenital defect characterized by primary failure of neural tube closure of the spinal column during the embryologic period. Cerebrospinal fluid (CSF) leak caused by MMC in the developing fetus can result in a constellation of anomalies that include hindbrain herniation and brain-stem abnormalities. The exposure of extruded spinal cord to amniotic fluid also poses a significant risk for inducing partial or complete paralysis of the body parts beneath the spinal aperture. A recent randomized trial demonstrated that open fetal surgery is effective in reducing the postnatal neurologic morbidity, as evidenced by decreased incidence and severity of postnatal hydrocephalus and reduced need for postnatal ventricular-peritoneal shunting. However, as open fetal surgery has been noticed to be associated with increased potential for maternal-fetal morbidities, innovative minimally invasive fetoscopic techniques to repair MMC are receiving growing attentions for their less invasiveness. Nonetheless, deploying patches through small trocar ports and unfolding patches for defect coverage can be extremely cumbersome and thus uncontrollably prolongs the surgical duration. Moreover, inert patches necessitate postnatal removal surgeries, which lead to higher surgical costs and psychological trauma to the infant and parents. The long-term effectiveness for some mesh-like patches to barrier the defect is also debating. There is an enormous need to obtain a ?smart? patch that is self-expanding, impermeable to cease the CSF leaking and biodegradable to accommodate the scheme of wound healing. Recently we have attempted to develop such a ?smart patch? for the fetoscopic procedure to repair MMC that hopefully addresses all the hurdles aforementioned concurrently. By blending two polymers that have been utilized in fabricating biodegradable spinal implants, we developed a new patch made with poly(?-caprolactone) (PCL) and poly(L-lactide) that possesses desired characteristics of shape retention, water-tightness, biocompatibility, affinity for cellular attachment, and biodegradation. The goal of the current project is to assess how the features of the newly designed patch can contribute to the protection of affected spinal cord that in turn alleviates complications associated with MMC defect. Using a sheep MMC model we have developed, we would like to further assess the efficacies of the new PLA/PCL patch in: (1) reducing the procedure time of fetoscopic coverage on MMC, (2) providing adequate barrier to stop CSF leak and protect the exposed spinal cord to mitigate the damage, which will help preserve and even improve the affected motor function, and (3) guiding and enhancing wound closure of MMC without tethering the spinal cord as our defined aims. If successful, our designed new patch will help advance fetoscopic approaches to become the most reliant procedure for the prenatal management of the MMC defect. This will greatly improve the outcome of the fetoscopic MMC repair, and facilitate the paradigm shifting for the surgical care of MMC.

Public Health Relevance

(Lay Summary) A recent randomized clinical trial for repairing open spinal bifida, a devastating neurologic congenital defect with open neural tube in fetus, showed that prenatal compared with postnatal repair has a great benefit to alleviate deficits of the central nerve system. The goal of the proposed study is to evaluate a newly developed patch that can specifically facilitate the fetoscopic coverage of the defect by concurrently overcoming hurdles associated with common surgical patches and in turn alleviates the associated complications.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS103992-01A1
Application #
9737628
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Morris, Jill A
Project Start
2019-04-01
Project End
2024-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Orthopedics
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221