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Purpose: Transforming growth factor beta (TGF-beta) bioactivity has been implicated as a potential regulator of the transition from scarless healing to scar formation in fetal wounds. Decorin is an extracellular matrix proteoglycan that regulates TGF-beta bioactivity and assists in collagen fibrillogenesis. To determine its role in scarless repair, the authors examined decorin expression in fetal fibroblasts, skin, and wounds., Methods: A single, full-thickness, 2-mm open wound was created on the dorsal surface of fetal rats at 16.5 days (E16) and 18.5 days (E18) gestational age (term, 21.5 days [E21]). Wounds were harvested at 24 and 72 hours (n = 12 wounds per time-point). Nonwounded fetal skin at E17, E19, and E21 was harvested for analysis of decorin expression during skin development and as controls for wounds. In addition, fetal (E14, E18) and adult dermal fibroblasts were cultured for in vitro analysis. Reduced-cycle, specific primer, reverse transcriptase polymerase chain reaction was performed to quantitate decorin expression., Results: Decorin expression increased rapidly with increasing gestational age in both fetal fibroblasts and skin. Expression was increased 22-fold in E18 fibroblasts (P <.002) and 300-fold in adult fibroblasts (P <.001) compared with E14 fibroblasts. In skin, expression increased 74% (P <.01) during the fetal wound healing transition period between E17 and E19. However, in E16 wounds (scarless), decorin expression decreased 59% (P <.006) at 24 hours and 45% (P <.02) at 72 hours. Decorin expression did not change in E18 (scar) wounds at 24 and 72 hours (P >.05)., Conclusions: Early gestation fetal fibroblasts and fetal skin express decorin at lower levels than late gestation fetal and adult fibroblasts and skin. Decorin expression is down-regulated in scarless (E16) compared with scar (E18) wounds. Thus, increased decorin expression is associated with both skin development and scar formation. Conversely, decreased decorin expression is associated with scarless repair., (Copyright 2001 by W.B. Saunders Company.)

The aim of this study was to determine whether the fetal alimentary tract shares the unique scarless healing properties of fetal skin. Full-thickness incisional gastric wounds were created and sutured closed in fetal lambs at 60, 75, and 120 days' gestation (full term, 145 days), and in adult control sheep. At the time of harvest, 14 days postwounding, dense fibrous adhesions were found intraperitoneally in all fetal and adult animals. Histologically, all fetal and adult gastric wounds healed with pronounced scar formation. In contrast to the adult wound, there was no significant inflammatory response in the fetal wounds. Because scar formed in the absence of inflammation in fetal gastric wounds, there is no obvious relation between scarring and the inflammatory response at this location. This study shows that not all fetal tissues exhibit scarless repair properties.

Intensive management of the fetus is limited by our inability to achieve access to the fetal circulation. Using laparoscopic surgery, we can maintain long-term access to the fetal circulation by extra-amniotic catheterisation of chorionic vessels in third-trimester monkeys and early-gestation sheep. We can sample fetal blood, continuously measure blood pressure, and infuse drugs without complications. Safe vascular access will permit assessment of fetal status during fetal surgical procedures and improve postoperative monitoring.

Fetoscopic techniques may broaden the indications for prenatal surgical intervention by obviating the risks of hysterotomy. For example, congenital obstructive uropathy has been treated by open vesicostomy and percutaneous catheter placement. The open approach is appropriate only for highly selected fetuses because of the inherent risks, whereas catheter drainage, though a safer procedure, is only useful for short-term therapy late in gestation due to frequent catheter obstruction and migration. The natural history of congenital obstructive uropathy mandates the need for improved therapy earlier in gestation, in order to salvage fetuses who would otherwise die of renal failure and pulmonary hypoplasia. We have developed a potential solution to this problem in which surgery is performed on the fetus without the risks of hysterotomy. Endoscopic fetal surgery uses a telescopic lens and operating instruments that are passed through small "ports" in the uterus. A bubble of CO2 is used to displace amniotic fluid and provides excellent visualization in a magnified field. This approach is considerably less invasive than open fetal surgery and, therefore, is less likely to provoke preterm labor. In this study we corrected obstructive uropathy in midgestation fetal lambs using a new, expandable wire mesh stent that is placed endoscopically and should provide more reliable bladder drainage than existing catheters. The fetoscopic surgical approach can potentially expand the indications for in utero surgery by decreasing fetal risks, facilitating intervention earlier in gestation, and reducing preterm labor. As a consequence, the potential now exists to correct non-life-threatening malformations in utero.