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Development and Characterization of a Poly (l-lactic acid)/ Poly (e-caprolactone) Self-Expanding Patch for Fetoscopic Repair of Myelomeningocele

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2018, PhD, University of Cincinnati, Engineering and Applied Science: Biomedical Engineering.
Myelomeningocele (MMC) is a neurologic defect characterized by failure of neural tube closure in the spinal column. This leads to cerebrospinal fluid leakage or contact with amniotic fluid, which can translate into sexual dysfunctions and paralysis after birth. The recently developed minimally-invasive technique for MMC repair is called fetoscopy, which involves a surgical patch, expanded for defect coverage on the fetus’ back. Currently used inert patches do not degrade after implantation, necessitating a post-natal removal surgery, while collagen-based patches employed in are associated with poor mechanical integrity. Also, these patches are not tailored for fetoscopic MMC repair, and their response in fetal environment is unexplored. Deployment and expansion of coiled patch using surgical tools at defect site is time-consuming and cumbersome. Some of these existing patches have mesh-like structure for tissue in-growth, which makes their barrier properties debatable. Upon implantation at defect site, the patch encounters amniotic fluid and body fluids, as well as fluid forces due to fetal movement in the womb. This necessitates analysis of biodegradability and mechanical response of the patch for its adaptability in fetoscopic MMC repair. Taking the above requirements into consideration, we designed a patch comprising a blend of poly (L-lactic acid) (PLA) and poly (ε-caprolactone) (PCL), both polymers approved by the U.S. Food and Drug Administration for hard and soft tissue repair in spine. Different PLA-PCL formulations were characterized for surface and thermal properties, and the ideal formulation was chosen as our designed patch based on aptitude for thermal expansion at in-vivo temperature (37&degC). This will enable self-expansion of the coiled patch at defect site, saving time and reducing difficulty level of surgery. The designed patch was characterized for barrier properties to ensure its watertight nature, and for biocompatibility after exposure to human foreskin fibroblasts, to confirm absence of solvent traces from fabrication. Bio-degradation of designed patch was studied in simulated fetal environment of human amniotic fluid. Patch strips were immersed in human amniotic fluid and subjected to a simulated fetal environment. An additional set of patch strips was immersed in phosphate-buffered saline as a time-paired control. Changes in weight, surface roughness, functional groups, crystallinity and mechanical properties were investigated at 4, 8, 12 and 16-week time points. Our principal findings indicate the progress of hydrolytic degradation in amniotic fluid, with brittle behavior observed at 16 weeks. However, no deterioration of mechanical and barrier properties was observed for application in fetoscopic MMC repair. We analyzed the biocompatibility of our patch in two in-vivo animal models. In the first one, we demonstrated the encapsulation of the patch with no immune reaction on subcutaneous implantation and in the second one we demonstrated compatibility of the patch as a dural substitute via laminectomy. The patches when in contact with the spinal cord as a dural substitute will not induce any adverse effect such as scar formation or tethering cord and functions of the spinal cord. The designed patch successfully fulfilled all requirements and serves as a standalone system to tackle impending hurdles of MMC repair.
Chia-Ying Lin, Ph.D. (Committee Chair)
Yoonjee Park, Ph.D. (Committee Member)
Jose Peiro (Committee Member)
Marepalli Rao, Ph.D. (Committee Member)
153 p.

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Citations

  • Tatu, R. R. (2018). Development and Characterization of a Poly (l-lactic acid)/ Poly (e-caprolactone) Self-Expanding Patch for Fetoscopic Repair of Myelomeningocele [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535635832679162

    APA Style (7th edition)

  • Tatu, Rigwed. Development and Characterization of a Poly (l-lactic acid)/ Poly (e-caprolactone) Self-Expanding Patch for Fetoscopic Repair of Myelomeningocele. 2018. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535635832679162.

    MLA Style (8th edition)

  • Tatu, Rigwed. "Development and Characterization of a Poly (l-lactic acid)/ Poly (e-caprolactone) Self-Expanding Patch for Fetoscopic Repair of Myelomeningocele." Doctoral dissertation, University of Cincinnati, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535635832679162

    Chicago Manual of Style (17th edition)