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J Pediatr Surg. 2019 Jan;54(1):80-85. doi: 10.1016/j.jpedsurg.2018.10.031. Epub 2018 Oct 5.

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

Author information

1
Department of Surgery, Yale University School of Medicine, New Haven, CT, USA. Electronic address: james.farrelly@yale.edu.
2
Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University, New Haven, CT, USA.
3
Department of Surgery, Yale University School of Medicine, New Haven, CT, USA; Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University, New Haven, CT, USA.
4
Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.

Abstract

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.

KEYWORDS:

Alginate microparticles; Fetal therapy; Myelomeningocele; Particle therapy; Spina bifida

PMID:
30414695
DOI:
10.1016/j.jpedsurg.2018.10.031
[Indexed for MEDLINE]

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