Improved Coverage of Mouse Myelomeningocele With a Mussel Inspired Reverse Thermal Gel.

BACKGROUND: Myelomeningocele (MMC) is an open neural tube defect of the spinal column. Our laboratory previously introduced a reverse thermal gel (RTG) as the first in situ forming patch for in utero MMC application. To overcome the challenges of anchoring the RTG in the wet amniotic environment to improve MMC coverage, we modified the RTG to mimic the underwater adhesive properties of mussels. We have separated this study into three separate hypotheses-based components: CONCLUSIONS: The DRTG demonstrates increased elasticity, cellular scaffolding properties, and improved MMC coverage in the Grhl3 mouse model. Future studies will be translated to the preclinical ovine model to evaluate this novel gel.

Intra-amniotic Injection of Poly(lactic-co-glycolic Acid) Microparticles Loaded with Growth Factor: Effect on Tissue Coverage and Cellular Apoptosis in the Rat Model of Myelomeningocele.

BACKGROUND: Myelomeningocele (MMC) is a devastating congenital neurologic disorder that can lead to lifelong morbidity and has limited treatment options. This study investigates the use of poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) loaded with fibroblast growth factor (FGF) as a platform for in utero treatment of MMC. STUDY DESIGN: Intra-amniotic injections of PLGA MPs were performed on gestational day 17 (E17) in all-trans retinoic acid-induced MMC rat dams. MPs loaded with fluorescent dye (DiO) were evaluated 3 hours after injection to determine incidence of binding to the MMC defect. Fetuses were then treated with PBS or PLGA particles loaded with DiO, bovine serum albumin, or FGF and evaluated at term (E21). Fetuses with MMC defects were evaluated for gross and histologic evidence of soft tissue coverage. The effect of PLGA-FGF treatment on spinal cord cell death was evaluated using an in situ cell death kit. RESULTS: PLGA-DiO MPs had a binding incidence of 86% and 94% 3 hours after injection at E17 for doses of 0.1 mg and 1.2 mg, respectively. Incidence of soft tissue coverage at term was 19% (4 of 21), 22% (2 of 9), and 83% (5 of 6) for PLGA-DiO, PLGA-BSA, and PLGA-FGF, respectively. At E21, the percentage of spinal cord cells positive for in situ cell death was significantly higher in MMC controls compared with wild-type controls or MMC pups treated with PLGA-FGF. CONCLUSION: PLGA MPs are an innovative minimally invasive platform for induction of soft tissue coverage in the rat model of MMC and may reduce cellular apoptosis.

Alginate microparticles loaded with basic fibroblast growth factor induce tissue coverage in a rat model of myelomeningocele.

BACKGROUND/PURPOSE: We sought to develop a minimally invasive intra-amniotic therapy for prenatal treatment of myelomeningocele (MMC) in an established rat model. METHODS: Time-dated pregnant rats were gavage-fed retinoic acid to induce MMC. Groups received intraamniotic injections at E17.5 with alginate particles loaded with fluorescent dye, basic fibroblast growth factor (Alg-HSA-bFGF), fluorescently tagged albumin (Alginate-BSA-TR), free bFGF, blank alginate particles (Alg-Blank), or PBS. Groups were analyzed at 3 h for specific particle binding or at term (E21) to determine MMC coverage. RESULTS: Alginate microparticles demonstrated robust binding to the MMC defect 3 h after injection. Of those specimens analyzed at E21, 150 of 239 fetuses (62.8%) were viable. Moreover, 18 of 61 (30%) treated with Alg-HSA-bFGF showed evidence of soft tissue coverage compared to 0 of 24 noninjected (P = 0.0021), 0 of 13 PBS (P = 0.0297), and 0 of 42 free bFGF (P = P < 0.0001). Scaffolds of aggregated particles associated with disordered keratinized tissue were observed covering the defect in 2 of 18 (11%) Alg-BSA-TR and 3 of 19 (16%) Alg-Blank specimens. CONCLUSIONS: Injection of microparticles loaded with bFGF resulted in significant soft tissue coverage of the MMC defect compared to controls. Alginate microparticles without growth factors might result in scaffold development over the fetal MMC. TYPE OF STUDY: Basic science. LEVEL OF EVIDENCE: N/A.

De Novo Spinal Dural Arteriovenous Fistula in a Patient with a Lipomyelomeningocele: Case Report.

BACKGROUND: Spinal dural arteriovenous fistula (AVF), the most common type of spinal vascular malformation, tends to manifest as progressive myelopathy over several years. Spinal dural AVFs are considered an acquired lesion and, in contrast to spinal arteriovenous malformations, are not often associated with other anomalies. The presence of a spinal dural AVF in the setting of a lipomyelomeningocele and tethered cord is extremely rare. Both lesions tend to cause similar symptoms, and patients with concomitant lesions generally require surgical intervention for both. CASE DESCRIPTION: A 57-year-old female with lifelong urinary incontinence and mild weakness in the left lower extremity presented with progressive worsening of left lower extremity weakness as well as worsening bowel and bladder incontinence. Magnetic resonance imaging (MRI) performed 4 years before our evaluation revealed a lipomyelomeningocele and a tethered cord; a new MRI demonstrated a new additional finding of flow voids suspicious of an underlying vascular malformation. Diagnostic angiography revealed a dural AVF fed by a left lateral sacral artery. Onyx embolization of the dural AVF was performed, and the patient improved steadily postoperatively without the need for surgically addressing the tethered cord. CONCLUSION: In this case report, we present evidence of de novo development of a spinal dural AVF associated with a lipomyelomeningocele. In addition, this is the second documented patient in the literature with a lipomyelomeningocele and concomitant dural AVF who did not undergo detethering of the cord as part of treatment.