An intricate problem during open human fetal surgery for spina bifida regards back skin closure, particularly in those cases where the skin defect is much too large for primary closure. We hypothesize that tissue engineering of fetal skin might provide an adequate autologous skin substitute for in utero application in such situations. Eight sheep fetuses of four time-mated ewes underwent fetoscopic skin biopsy at 65 days of gestation. Fibroblasts and keratinocytes isolated from the biopsy were used to create fetal dermo-epidermal skin substitutes. These were transplanted on the fetuses by open fetal surgery at 90 days of gestation on skin defects (excisional wounds) created during the same procedure. Pregnancy was allowed to continue until euthanasia at 120 days of gestation. The graft area was analyzed macroscopically and microscopically. The transplanted fetal dermo-epidermal skin substitutes was well discernable in situ in three of the four fetuses available for analysis. Histology confirmed healed grafts with a close to natural histological skin architecture four weeks after in utero transplantation. This experimental study generates evidence that laboratory grown autologous fetal skin analogues can successfully be transplanted in utero. These results have clinical implications as an analogous procedure might be applied in human fetuses undergoing prenatal repair to facilitate primary skin closure. Finally, this study may also fertilize the field of fetal tissue engineering in general, particularly when more interventional, minimally invasive, and open fetal surgical procedures become available.

中文翻译：

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绵羊模型中胎儿皮肤的生物工程和子宫内移植：在人类胎儿脊柱裂修复中临床应用的关键一步。

在开放式人类胎儿外科手术中脊柱裂的一个复杂问题是背部皮肤闭合，尤其是在那些皮肤缺陷太大而无法进行初级闭合的情况下。我们假设胎儿​​皮肤的组织工程可以为这种情况下的子宫内应用提供足够的自体皮肤替代物。在妊娠65天时，对八只母羊的八只母羊进行了镜下活检。从活检中分离出的成纤维细胞和角质形成细胞被用于创建胎儿真皮-表皮皮肤替代品。在妊娠90天时，通过开放式胎儿手术将它们移植到胎儿身上，以消除在相同手术过程中产生的皮肤缺损（切除伤口）。允许妊娠持续至妊娠120天安乐死。宏观和微观分析移植物区域。移植的胎儿真皮-表皮皮肤替代品在可用于分析的四只胎儿中的三只中，在原位可被很好地辨别。组织学证实子宫内移植后四周，移植物愈合后的皮肤具有接近自然的皮肤结构。这项实验研究产生的证据表明，实验室培养的自体胎儿皮肤类似物可以成功地移植到子宫内。这些结果具有临床意义，因为类似的方法可能适用于进行产前修复的人类胎儿，以促进原发性皮肤闭合。最后，这项研究也可能总体上为胎儿组织工程领域提供了便利，特别是在可以进行更多干预，微创和开放式胎儿外科手术的情况下。