Tissue Engineering Strategies for Fetal Myelomeningocele Repair in Animal Models

Abstract

Myelomeningocele (MMC), the most severe form of spina bifida, is a common and devastating malformation. Over two decades of experimental work in animal models have led to the development and clinical application of open fetal surgery for the repair of the MMC defect. This approach offers improved neurofunctional outcomes and is now a clinical option for the management of prenatally diagnosed MMC in selected patients. However, there are still opportunities for further improvement in the prenatal treatment of MMC. A less invasive approach would allow for an application earlier in gestation, with a reduction in maternal and fetal risks and the potential for reduced neurological injury. Tissue engineering offers a realistic and appealing alternative approach for the prenatal treatment of MMC. This review discusses the rationale for tissue engineering in MMC, addresses recent experimental progress and describes potential future directions.

Safety and efficacy of fetal surgery techniques to close a spina bifida defect in the fetal lamb model: A systematic review

“…As new clinical techniques are introduced, it would seem logic to preclinically validate them against this experimental standard in the SB fetal lamb model. Such experiments should use standardized methods for both timing of the experiments, ie, induction and closure of the lesion, and objectively evaluating the effects of surgical closure …”

Cryopreserved human umbilical cord versus biocellulose film for prenatal spina bifida repair in a physiologic rat model

“…This ongoing inflammation convolutes the analysis of the repair site at the time of euthanasia. Current approaches to prenatal SB repair have evaluated collagen, gelatin, polylactic acid, acellular scaffolds, and autologous amniotic membrane as regenerative patch materials . With the exception of one, all of the previous studies were performed on sheep with surgically created SB lesions, not in a physiologic model like the RA rat induced SB model.…”

Fetal surgical intervention for myelomeningocele: lessons learned, outcomes, and future implications

“…Follow‐up studies provided clear evidence for the ‘two‐hit hypothesis’ . Moreover, the fetal rat is also large enough to allow evaluations of various prenatal coverage strategies …”