Coverage of Fetal Skin Defects With a Collagen Biomatrix Loaded With Growth Factors in a Sheep Model

Abstract

Purpose Patients with spina bifida suffer from severe morbidity. In former animal studies we have shown that coverage of a surgically created spina bifida during the fetal period can result in decreased morbidity after birth: less incontinence and less paralysis of the hindlimbs.1 However, to enhance skin regeneration, i.e. more angiogenesis and cell attraction, the biomatrix needs to be improved. Aim of this study is to evaluate the coverage of fetal skin defects with a collagen biomatrix, a biomatrix loaded with heparin and growth factors (VEGF and FGF) and wound healing without a biomatrix. Material and Methods At 79 days' gestation, 3 skin defects (O 10 mm) were created on the back of 11 fetal lambs. One defect was left uncovered, one was covered with a collagen biomatrix, and one with a biomatrix loaded with glycosaminoglycans (heparin) and growth factors (VEGF and FGF-2). Lambs were sacrificed at 93 (n = 4), 107 (n = 3) and 138 (n = 4) days' gestation. The skin defects were macroscopically and histologically examined. Results Macroscopic evaluation revealed wound healing mainly by wound contraction for the uncovered defects. The covered defect with plain biomatrix showed partially contraction and the covered defect with growth factor loaded biomatrix showed minor contraction. Histological evaluation revealed increased angiogenesis and keratinocyt growth in the growth-factor-loaded biomatrix. Additionally, decreased degradation of the biomatrix was seen in these defects, i.e. at 138 days' gestation the biomatrix was still largely present. Overall, improved maturation of skin tissue was seen in time. Conclusions Coverage of fetal skin defects with a VEGF and FGF-2 loaded collagen biomatrix resulted in less wound contraction, increased angiogenesis and keratinocyt growth. This biomatrix can be useful in coverage of large spina bifida defects to improve neonatal outcome. 1:Eggink et al. Fetal Diagnosis and Therapy 2005 Sep-Oct;20(5):335-40.