BACKGROUND:Fibroproliferative disorders, which include hypertrophic scars and keloids, represent deviations from the normal process of wound healing. The fibrogenic cytokines have been associated with excessive scarring. It has been proposed that placing silicone in contact with hypertrophic scars may prove to be an effective form of treatment. This may be a result of downregulating fibroblasts and/or decreasing the fibrogenic cytokines. An in vitro model to study wound contraction is a fibroblast populated collagen lattice (FPCL). This study used FPCL as a method to study the effect of silicone sheeting on hypertrophic scar fibroblasts.METHODS:Fibroblast cultures were obtained and collagen lattices were prepared. Silicone sheeting was placed over the collagen matrix versus Saran wrap used as a treatment control. The amount of gel contraction was measured every 24 hours for five days. The supernatant obtained from the culture medium following completion of the FPCL portion of the experiment was then used in an immunoassay for TGFbeta2.RESULTS:A statistically significant decrease in amount of FPCL contraction occurred between three of the four brands of silicone sheets used compared to untreated control or Saran wrap treated FPCL. The immunoassay for TGFbeta2 showed a statistically significant decrease with all four types of silicone sheeting.CONCLUSION:FPCLs populated with burn hypertrophic scar fibroblasts exposed to silicone sheeting have decreased contraction compared to an unexposed control and Saran wrap treated control. In addition, TGFbeta2 is downregulated in the silicone exposed group. It appears that silicone sheeting may act by downregulating fibroblasts and decreasing fibrogenic cytokines.

The PSEF Device and Technique Assessment Committee evaluates information on new plastic surgery devices and techniques, or new information on existing technology and approaches, and reports the findings to the membership. If there are any timely and emerging devices or techniques that you feel the committee should investigate, please send your suggestion to the PSEF DATA Committee, 444 East Algonquin Road, Arlington Heights, Ill. 60005.

A successful free tissue transfer of serratus anterior muscle, to provide coverage for an open ankle defect in a pregnant patient, is described. Microvascular surgery in the presence of a viable pregnancy demands considerations unique to this situation. Although rarely possible, an attempt should be made to plan surgery to coincide with the second trimester, to lessen the risk of anesthesia to the fetus. Maternal positioning, fluid balance, and aspiration precautions need to be critically addressed. Close perioperative monitoring by an obstetrician is essential. The condition of pregnancy results in a hypercoagulable state that may lead to an increased risk of anastomotic failure. The use of anticoagulants results in increased risk of bleeding, not only for the patient but also for the fetus, as well as risk of teratogenic effects. Closely monitored heparin is considered safe in pregnancy as is low-molecular-weight dextran and low-dose aspirin. Additional considerations include the use of narcotics and sedatives for comfort postoperatively, as well as antibiotic choices, if indicated.

Periprosthetic breast capsules composed of fibrotic collagenous material with increased collagen production are not dissimilar to other fibrotic conditions occurring in other organs. Fibrosis in the lung, liver, kidney, and skin has been associated with overproduction of the fibrogenic isoforms of transforming growth factor beta (TGF-beta1 and TGF-beta2). If periprosthetic breast capsules contained high levels of these cytokines, possibly new treatment approaches for capsular contraction could be proposed. Breast implant capsules of 35 patients harvested at the time of explantation were examined using indirect immunohistochemistry. Staining intensity for TGF-beta1 and TGF-beta2 was measured in all specimens. Immunohistochemical staining for TGF-beta1 and TGF-beta2 revealed that these two cytokines were present in all capsules analyzed. Minimal TGF-beta1 and TGF-beta2 were found in normal breast tissue. Levels of control vs. TGF-beta1 and control vs. TGF-beta2 were significant (p = 0.004 and p < 0.001 respectively). The presence of TGF-beta isoforms that are known to be fibrogenic may suggest new therapeutic approaches, which are being investigated for other fibrotic conditions.

Previous studies have shown the osteogenic potential of negatively charged Sephadex beads when used to heal osseous defects in an animal model. The present study examined the effect of adding the growth factors transforming growth factor‐β1 and basic fibroblast growth factor to negatively charged Sephadex beads and neutral (non‐osteogenic) Sephadex beads in a critical size calvarial defect in rabbits. New Zealand White rabbits were divided into six groups of five rabbits; 15 mm parietal defects were created and filled with either negatively charged Sephadex beads (three groups) or neutral Sephadex beads (three groups). Each group received either 2 µg of transforming growth factor‐β1, 1 µg of basic fibroblast growth factor, or buffer (control). Animals were killed at 5 weeks, and their calvaria were submitted to plain radiographic and histomorphometric analyses. Defects treated with negatively charged Sephadex beads produced significantly more new trabecular bone than neutral Sephadex beads (p < 0.01), whereas the neutral beads treated with transforming growth factor‐β1 formed significantly more bone than controls. The addition of transforming growth factor‐β1 to negatively charged beads resulted in near closure of the craniotomy defect. The application of transforming growth factor‐β1 to this model resulted in significantly more ectopic bone (p < 0.01) outside the defect on the dural and periosteal surfaces. Basic fibroblast growth factor, in the dose used, appeared to have an inhibitory effect on new bone formation fostered by negatively charged Sephadex beads. This study suggests that the addition of transforming growth factor‐β1 to the known osteoconductive matrix of negatively charged Sephadex beads may be therapeutically useful in nonhealing bony defects.

Transforming growth factor‐β2 promotes healing in a variety of animal models and exhibits clinical effects thought to be mediated by connective tissue formation. Two clinical trials were conducted to evaluate the safety and effect of transforming growth factor‐β2 purified from bovine bone and delivered topically to venous stasis ulcers three times per week for up to 6 weeks by means of a lyophilized collagen vehicle. The first was an open‐label trial comparing transforming growth factor‐β2 purified from bovine bone (0.5 µg/cm2) with a placebo consisting of lyophilized collagen vehicle‐without active drug. After no safety issues arose in that trial, a prospectively randomized, closed‐label, observer‐blinded, three‐armed trial was conducted to compare bovine transforming growth factor‐β2 (2.5 µg/cm2) with the collagen matrix placebo vehicle and with a standard dressing. Standardized elastic compression was applied to all test extremities. The rate of reduction of ulcer area as measured by planimetry was the primary measure of effect. No serious safety‐related events occurred in either trial. Clinical evaluation suggested that improvement in the quality and quantity of granulation tissue appeared to precede epithelialization of ulcers treated with bovine transforming growth factor‐β2. In both studies, treatment with bovine transforming growth factor‐β2 appeared to have a positive effect on the rate of ulcer closure, whereas ulcers in the control groups continued to exhibit impaired healing. In the open‐label study, the mean rate of closure of ulcers treated with bovine transforming growth factor‐β2 was significantly greater than that of ulcers treated with placebo. There was likewise enhanced reduction in ulcer area in the ulcers treated with bovine transforming growth factor‐β2 in the second trial. However, because of a higher variability in patient response and a greater placebo effect, the difference was not significant. The placebo was not worse than the standard care arm, thereby showing that the vehicle is not injurious to healing. The combined results of the two trials suggest that, at doses of 0.5 to 2.5 µg/cm2, bovine transforming growth factor‐β2 is safe as a topically applied agent in a collagen matrix vehicle and can have a positive effect on closure of venous stasis ulcers. Large multicenter trials appear to be indicated to evaluate fully the potential utility of transforming growth factor‐β2 in accelerating closure of chronic dermal ulcers.