Broadley K N, Aquino A M, Hicks B, Ditesheim J A, McGee G S, Demetriou A A, Woodward S C, Davidson J M
Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Biotechnol Ther. 1989;1(1):55-68.
Two models of wound repair compared the effect of defined, recombinant growth factors on the rate of wound repair in both normal and streptozotocin-induced diabetic rats: subcutaneous implantation of polyvinyl alcohol sponges and incisional wounding. Transverse incisional wounds were made on the dorsal surface of rats and closed with steel sutures. Three days postwounding the rats received a single injection of either transforming growth factor-beta or vehicle alone directly into the wound site. Animals were sacrificed 7, 14, and 21 days postwounding, and fresh and formalin-fixed wound tensile strength were measured. Diabetic rats had expected defects in wound repair, including decreased granulation tissue and reduced amounts of collagen, protein, and DNA. Fresh tensile strength of the diabetic incisions was 53% of normal on Day 7 (p < or = .01) and 29% of normal on Day 21. Fixed tensile strength was 41% of normal on Day 7 (p < or = .01) and fell to 78% of normal by Day 21 (p < or = .01), suggesting that collagen concentrations of diabetic wounds increased towards normal but did not undergo maturation. TGF beta produced a moderate increase in tensile strength of fresh and fixed wounds of diabetic rats, but not to the levels of wounds in untreated normal rats. Sponges fill with granulation tissue, their reproducible rate of organization being measured by histological and biochemical methods. A single injection into sponges 3 days postimplantation of basic fibroblast growth factor, transforming growth factor-beta, or vehicle only, was evaluated at 7 and 9 days postimplantation. In the sponge model, bFGF and TGF beta were each able to induce significant increases in the accumulation of granulation tissue in both diabetic and normal rats. TGF beta increased the collagen content of sponges by 136% in sponges from diabetic animals (p < or = .001), thereby raising the collagen content to that of normal control wounds, while stimulating a 49% (p < or = .02) increase in sponges from normal animals on Day 9. By contrast, the response to bFGF was predominantly an increase in the protein and DNA content of the sponges. These results emphasize the differential effects of the two cytokines in accelerating healing under conditions of defective wound repair.
聚乙烯醇海绵皮下植入和切开创伤。在大鼠背部表面制造横向切口创伤，并用钢缝线缝合。创伤后3天，大鼠在伤口部位直接接受单次注射转化生长因子-β或仅注射赋形剂。在创伤后7天、14天和21天处死动物，测量新鲜和福尔马林固定后的伤口抗张强度。糖尿病大鼠在伤口修复方面存在预期缺陷，包括肉芽组织减少以及胶原蛋白、蛋白质和DNA含量降低。糖尿病切口的新鲜抗张强度在第7天为正常的53%（p≤0.01），在第21天为正常的29%。固定抗张强度在第7天为正常的41%（p≤0.01），到第21天降至正常的78%（p≤0.01），这表明糖尿病伤口的胶原蛋白浓度向正常水平增加，但未成熟。转化生长因子-β使糖尿病大鼠新鲜和固定伤口的抗张强度适度增加，但未达到未处理正常大鼠伤口的水平。海绵充满肉芽组织，通过组织学和生化方法测量其可重复的组织形成速率。在植入后3天向海绵中单次注射碱性成纤维细胞生长因子、转化生长因子-β或仅注射赋形剂，并在植入后7天和9天进行评估。在海绵模型中，碱性成纤维细胞生长因子和转化生长因子-β均能在糖尿病大鼠和正常大鼠中显著增加肉芽组织的积累。转化生长因子-β使糖尿病动物海绵中的胶原蛋白含量增加136%（p≤0.001），从而使胶原蛋白含量提高到正常对照伤口的水平，同时在第9天刺激正常动物海绵中的胶原蛋白含量增加49%（p≤0.02）。相比之下，对碱性成纤维细胞生长因子的反应主要是海绵中蛋白质和DNA含量的增加。这些结果强调了在伤口修复缺陷的情况下，两种细胞因子在加速愈合方面的不同作用。
