We evaluated the effectiveness of basic fibroblast growth factor (bFGF) in inhibiting wound contraction, both alone and in combination with collagen matrix, using a simulated in vivo delayed healing type model. We also studied the mechanisms involved in this inhibition in in vitro experiments using fibroblast populated collagen gels. As a result, we were able to demonstrate that both collagen matrix and bFGF significantly inhibited wound contraction; especially, bFGF acted in a dose-dependent fashion. Interestingly, their combination was much more effective than either collagen matrix or bFGF alone, a finding that was supported by the histopathological data. Wounds treated with collagen matrix, but not control wounds, showed horizontal rearrangement of collagen fibers in dermis as well as evidence of fibroblast proliferation, which was not observed in scar regions surrounded by normal dermis. Using fibroblast-populated collagen gel contraction as an in vitro model, we found that bFGF significantly inhibited contraction. Taking all these results together, it was concluded that collagen matrix is useful not only as a carrier of cytokines such as bFGF, but also for the quick closure of chronic wounds, thereby preventing contracture, which remains one of the most challenging problems in treating this type of wound. Application of bFGF-treated collagen matrix to chronic wounds such as decubitus, and diabetic and leg ulcers may prove to be highly beneficial in clinical practice.
Excessive wound contraction is known to lead to pathological wound contracture. Using a rabbit model, we applied a bovine type I collagen matrix sponge as a dermal substitute and human epidermal growth factor to full-thickness excisional wounds. Wound contraction was assessed 14 and 28 days after wounding. It was found that both collagen matrix and epidermal growth factor significantly inhibited wound contraction (p < 0.001) in all wounds treated with collagen matrix alone or treated with 0.1 and 1 microg of epidermal growth factor 28 days after wounding. Interestingly, the combination of collagen matrix with epidermal growth factor strongly inhibited wound contraction over matrix alone (p < 0.01 on day 28). Histological analyses showed a regular horizontal arrangement of collagen fibers in the dermis under wounds treated with these substances but not under untreated wounds. Furthermore, using a fibroblast-populated collagen gel, the direct inhibitory effect of epidermal growth factor on gel contraction by fibroblasts was also observed. Collagen gels without stimulation contracted to 29.5 +/- 0. 6% of their original size, as determined 6 days after culturing. At 3 days or more, epidermal growth factor inhibited collagen gel contraction by fibroblasts (after 6 days: 34.2 +/- 1.8%, p > 0.05; 36.5 +/- 2.8%, p < 0.05; and 39.8 +/- 2.1%, p < 0.001 at 1, 10, and 100 ng/ml of epidermal growth factor, respectively). In conclusion, collagen matrix and epidermal growth factor, particularly in combination, may be useful in the prevention of wound contracture.
Our new surgical procedure with two triangular flaps for macrostomia repair allows us to achieve all three therapeutic goals, including formation of symmetric lips and commissures of the mouth, reconstruction of the orbicularis muscle of mouth to restore labial function, and reconstruction of the commissure of the mouth with a natural looking contour. Furthermore, the position of the commissure of the mouth can be adjusted intraoperatively according to the extent of macrostomia. As reported here, our method provides very satisfactory clinical results and is relatively easy to perform. Thus, we believe that our method can serve as a standard for the surgical treatment of macrostomia.
Hydroxyapatite ceramic implants were used in the reconstruction of very large and complex-form cranial bone defects in nine patients. The bone defects were the result of craniectomy after infections and other complications such as severe brain edema, after neurosurgery, and as a result of trauma, subdural hemorrhage, and surgery for brain tumor. The size, shape, and curvature of the hydroxyapatite ceramic implants were determined based on high-precision, full-scale models fabricated through a laser lithographic molding method by using computed tomographic data. The use of this method allowed the fabrication of hydroxyapatite ceramic implants of shapes that accurately matched the area of bone defect, allowing for a minimum of adjustment during the operation even with a complex-form implantation. Not only were good cranial contour reconstructed and aesthetically satisfactory results obtained in the cases treated by incorporating this series of techniques, but neurologic conditions present in some cases were also improved to some extent. The postoperative course has been steady for all nine patients, with no blood transfusions required during or after the operations and no implants requiring removal because of infection or other postoperative complications. The average length of postoperative hospitalization for the nine cases was 11.7 days, remarkably short considering the clinical conditions.
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