• J. Am. Coll. Surg. · Jun 2022

    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.

    • Nathan L Maassel, Douglas H Wu, Nicholas K Yung, Tory Bauer-Pisani, Mary Elizabeth Guerra, Sarah J Ullrich, Mark SaltzmanWWDepartment of Biomedical Engineering, School of Engineering and Applied Science (Saltzman), Yale University School of Medicine, New Haven, CT., and David H Stitelman.
    • Department of Surgery (Maassel, Yung, Guerra, Ullrich), Yale University School of Medicine, New Haven, CT.
    • J. Am. Coll. Surg. 2022 Jun 1; 234 (6): 1010-1019.

    BackgroundMyelomeningocele (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 DesignIntra-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.ResultsPLGA-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.ConclusionPLGA MPs are an innovative minimally invasive platform for induction of soft tissue coverage in the rat model of MMC and may reduce cellular apoptosis.Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.

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