Werner, Sabine, and Richard Grose. Regulation of Wound Healing by Growth Factors and Cytokines. Physiol Rev 83: 835–870, 2003; 10.1152/physrev.00032.2002.—Cutaneous wound healing is a complex proce...

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Regulation of Wound Healing by Growth Factors and Cytokines

Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous growth factors, cytokines and chemokines. Of particular importance is the epidermal growth factor (EGF) family, transforming growth factor beta (TGF-beta) family, fibroblast growth factor (FGF) family, vascular endothelial growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), interleukin (IL) family, and tumor necrosis factor-alpha family. Currently, patients are treated by three growth factors: PDGF-BB, bFGF, and GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other growth factors may soon be available to patients. This review will focus on the specific roles of these growth factors and cytokines during the wound healing process.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1524-475X.2008.00410.x

Growth factors and cytokines in wound healing.

Inflammation in wound repair: molecular and cellular mechanisms.

The trial was stopped for efficacy of prenatal surgery after the recruitment of 183 of a planned 200 patients. This report is based on results in 158 patients whose children were evaluated at 12 months. The first primary outcome occurred in 68% of the infants in the prenatal-surgery group and in 98% of those in the postnatalsurgery group (relative risk, 0.70; 97.7% confidence interval [CI], 0.58 to 0.84; P<0.001). Actual rates of shunt placement were 40% in the prenatal-surgery group and 82% in the postnatal-surgery group (relative risk, 0.48; 97.7% CI, 0.36 to 0.64; P<0.001). Prenatal surgery also resulted in improvement in the composite score for mental development and motor function at 30 months (P = 0.007) and in improvement in several secondary outcomes, including hindbrain herniation by 12 months and ambulation by 30 months. However, prenatal surgery was associated with an increased risk of preterm delivery and uterine dehiscence at delivery. Conclusions Prenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months but was associated with maternal and fetal risks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00060606.)

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A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele

Background Monochorionic twin pregnancies complicated by severe twin-to-twin transfusion syndrome at midgestation can be treated by either serial amnioreduction (removal of large volumes of amniotic fluid) or selective fetoscopic laser coagulation of the communicating vessels on the chorionic plate. We conducted a randomized trial to compare the efficacy and safety of these two treatments. Methods Pregnant women with severe twin-to-twin transfusion syndrome before 26 weeks of gestation were randomly assigned to laser therapy or amnioreduction. We assessed perinatal survival of at least one twin (a prespecified primary outcome), survival of at least one twin at six months of age, and survival without neurologic complications at six months of age on the basis of the number of pregnancies or the number of fetuses or infants, as appropriate. Results The study was concluded early, after 72 women had been assigned to the laser group and 70 to the amnioreduction group, because a planned interim analysis demonstr...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa032597

Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome

ContextHindbrain herniation occurs in a large percentage of children with myelomeningocele
and is the leading cause of death in this population. The effect of early
fetal closure of myelomeningocele on hindbrain herniation is unknown.ObjectiveTo determine whether early fetal closure of myelomeningocele affects
hindbrain herniation.DesignCase series of patients undergoing fetal myelomeningocele closure with
serial measurements of hindbrain herniation and a mean follow-up of 182 days.SettingTertiary care medical center.ParticipantsTen patients undergoing fetal myelomeningocele closure at 22 to 25 weeks'
gestation between March 1998 and February 1999.Main Outcome MeasuresNeed for shunt placement; degree of hindbrain herniation (grades 0-3)
found on magnetic resonance imaging (MRI) performed prior to surgery and 3
and 6 weeks after fetal surgery, as well as shortly after birth; gestational
age at delivery.ResultsAll initial fetal MRI scans performed at 19 to 24 weeks' gestation showed
significant (grade 3) cerebellar herniation and absence of spinal fluid spaces
around the cerebellum. Six fetuses were delivered electively at 36 weeks'
gestation after lung maturity was established. The other 4 were delivered
prematurely, at 25, 30, 30, and 31 weeks of gestation, and the 25-week gestation
neonate died. All 9 surviving neonates showed improvement in the hindbrain
hernia at the 3-week postoperative fetal scan (grade 2, n = 4; grade 1, n
= 5). On the postnatal scan, all patients showed grade 1 hindbrain herniation.
Only 1 patient required placement of a ventriculoperitoneal shunt.ConclusionIn this series of patients, fetal myelomeningocele closure resulted
in improvement in hindbrain herniation as demonstrated by serial MRI scans.

https://jamanetwork.com/journals/jama/articlepdf/192109/joc91537.pdf

Timothy M. Crombleholme

Papers

Improvement in hindbrain herniation demonstrated by serial fetal magnetic resonance imaging following fetal surgery for myelomeningocele.

The EXIT procedure: Experience and outcome in 31 cases

Diminished interleukin 6 (IL-6) production during scarless human fetal wound repair.

Fetal wound repair results in scar formation in interleukin-10-deficient mice in a syngeneic murine model of scarless fetal wound repair.

Treatment of severe congenital diaphragmatic hernia by fetal tracheal occlusion: clinical experience with fifteen cases.