Basic fibroblast growth factor and epidermal growth factor reverse impaired ulcer healing of the rabbit oral mucosa

BACKGROUND: The therapies for refractory ulcers on the oral mucosa are symptomatic and very unsatisfactory. We hypothesized that application of growth factors might be able to achieve successful remission of the lesion. We evaluated the effects of systemic administration and topical application of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on impaired wound healing of ulcers in the rabbit gingiva. METHODS: Almost uniform round ulcers could be created on the gingiva of the rabbits by chemical injury with acetic acid. When the submandibular glands were removed or i.v. injection of cisplatin (CDDP) and peplomycin sulfate was performed before ulcer formation, healing of the ulcers took longer than in untreated rabbits. To ascertain whether or not human EGF and bFGF affect rabbit cells, we first examined the effects of EGF and bFGF on the proliferation of the cells derived from rabbit gingiva. We then applied EGF or bFGF in these impaired healing models. RESULTS: EGF and bFGF promoted proliferation of the fibroblasts, and EGF also promoted proliferation of the keratinocytes isolated from gingival tissue of rabbits in vitro. Systemic injections of EGF and bFGF in rabbits, which had their submandibular glands removed, and topical application of bFGF accelerated healing of ulcers created in rabbits injected with CDDP and peplomycin sulfate. The ability of bFGF to promote the healing of ulcers was much greater than that of EGF. CONCLUSION: Basic FGF may be effective for refractory oral mucosal lesions.     

Regulation of fibroblast-induced collagen gel contraction by interleukin-1β

Fibroblasts incorporated within collagen gels induce a cell-mediated contraction of the gel to form a three-dimensional, tissue-like structure by a mechanism thought to mimic wound contraction in vivo . In this study a gel contraction model was used to investigate the ability of fibroblasts derived from adult gingiva, adult skin and fetal skin to organise a collagen matrix. In addition the effects of interleukin-1β (IL-1β) on the contraction process was also investigated. Over the concentration range 5-50 U/ml, IL-1β induced a statistically significant inhibition of gel contraction in all fibroblast cell types ( P <0.05), although fetal fibroblasts appeared least responsive and gingival fibroblasts most responsive to the inhibitory effects of this cytokine. Comparison of gel contraction by the different fibroblast strains indicated that fetal and gingival fibroblasts shared similar contraction kinetics. For the adult skin fibroblasts, three of five strains studied showed significantly diminished levels of gel contraction compared to fetal and gingival cells. This apparent difference in fibroblast phenotype may, at least in part, explain the fetal-like wound healing pattern seen in the oral mucosa.     

Monitoring pressure ulcer healing in persons with disabilities.

Pressure ulcers are a high-risk, high-volume, and high-cost problem for persons with disabilities. This article describes four tools published in the literature and reports the validity, reliability, strengths, and limitations of each. These tools include the Pressure Ulcer Scale for Healing (PUSH), the Pressure Sore Status Tool (PSST), the Sussman Wound Healing Tool (SWHT), and the Sessing Scale. Rehabilitation nurses should use a consistent framework with accurate quantification to assess, document, and monitor changes in pressure ulcers over time. Such a measurement tool must prove valid for the disabled population in which the tool is used. This will enable healthcare providers to communicate more effectively and evaluate the therapeutic plan of care.     

重组人血小板源性生长因子增加细胞外信号调节激酶磷酸化促进糖尿病大鼠全层皮肤缺损创面愈合

目的 在体观察重组人血小板源性生长因子（recombinant human platelet—derived growth factor，rhPDGF）促进糖尿病大鼠全层皮肤缺损创面修复可能涉及的细胞和分子机制，研究其可能涉及的信号通路。方法 26只糖尿病大鼠，每只动物背部制备4个全层皮肤缺损创面，选取其中52个创面，随机分成3组，即对照组，创面自然愈合；rhPDGF治疗组，创面rhPDGF用量为7．0μg／cm^2；赋形剂组，创面用等量赋形剂凝胶。观察治疗后3、7和14d创面肉芽形成、胶原沉积、再上皮化速率以及炎性细胞浸润情况，并采用免疫荧光和免疫组织化学技术观察创面周围和创面修复细胞内细胞外信号调节激酶1／2（extracellular signal—regulated kinase1／2，ERK1／2）磷酸化和增殖细胞核抗原（proliferative cell nuclear antigen，PCNA）的表达。结果 组织学观察，rhPDGF治疗组创面可见大量炎性细胞浸润，毛细血管胚芽及成纤维细胞明显多于另两组（P〈0．05）；胶原沉积明显，肉芽组织生长活跃，创面收缩显著，与对照组比较差异有统计学意义（P〈0．05）。免疫学研究显示，应用rhPDGF7～14d后，rhPDGF治疗组ERK1／2明显强于对照组和赋形剂组（P〈0．05）；且损伤后3～7d rhPDGF治疗组修复细胞PCNA的表达明显高于对照组和赋形剂组（P〈0．05）。结论 rhPDGF促糖尿病大鼠刨面愈合的作用部分是通过ERK1／2信号通路的磷酸化来完成的。     

The effect of sucralfate,an agent for gastroprotection on the healing of split thickness skin graft donor sites

Skin is the most commonly used tissue for the transplantation. A meticulous care of the donor site is needed to prevent scarring, delayed healing, and pain. Various agents and dressing materials have been reported to help healing of skin graft donor sites. Sucralfate is an extensively used agent, which provides acute gastroprotection and acceleration of chronic ulcer healing. In this study, we assessed the effects of topical sucralfate on the healing of the split thickness skin graft donor sites in a prospective comparative way. The study was carried out on 32 randomly chosen patients undergoing surgery for various causes and requiring split thickness skin graft resurfacing. The upper halves of the skin graft donor sites on the thighs were simply covered with paraffin gauze and the lower half was covered with sucralfate-soaked paraffin gauzes. The day of full epithelization varied from 6 to 9 days and 8–12 days on the sucralfate-applied areas and on the control sites, respectively. The mean value of the healing was 7.01 days in the studied lower halves and 10.8 days in the upper halves. The healing rate was strikingly faster and less painful on the sucralfate-applied areas. We were able to discharge patients earlier than usual, and patients’ comfort increased. It seems that sucralfate is a promising topical agent to increase the healing rate and decrease the incidence of associated problems such as pain and hypertrophic scar.     

碱性成纤维细胞生长因子（bFGF）加速猪背部创伤修复的实验研究

实验采用猪背部创伤模型，观察重组的碱性成纤维细胞生长因子（ｂＦＧＦ）对创伤修复的作用。在无菌条件下用特制打孔器在猪背部切割皮肤，形成２．５ｃｍ２的园型创面。将１５０个创面分成５组，分别以ｂＦＧＦ（６０ｕ／ｃｍ２创面），ｂＦＧＦ（（６０ｕ／ｃｍ２创面）加ＳＤ－Ａｇ、ＳＤ－Ａｇ、生理盐水以及不治疗等方法处理，每间隔一天换药一次。实验结果表明，ｂＦＧＦ具有显著促进肉芽组织生长、加速创面再上皮化率以及增加创面愈合组织抗张力强度等作用。ＦＧＦ显著促修复效应的确切机制尚不完全清楚，可能包括直接与间接效应两方面。     

Effect of hyaluronan on the healing of partially ruptured anterior cruciate ligament of rabbits

The midportion of the anterior cruciate ligament (ACL) of rabbits was partially transected, and the effect of hyaluronan (HA) on its healing was determined. A 1% solution of HA (HA group) or physiological phosphate-buffered saline (control group) was administered intraarticularly, at 0.1 ml/kg body weight, once a week from 1 week after the operation. Two, 4, and 6 weeks after the initiation of HA administration, the ACLs were examined grossly, histologically and immunohistochemically. At 2 weeks, the lacerated portions were completely covered with scar-like tissue in both groups. These tissue areas were smaller in the HA group than in the control group. Histologically in the HA group, the regularity of collagen fibers (indicating the maturity of regenerated collagen fibers) had increased compared to findings in the control group, and the number of fibroblastic cells decreased gradually at a significantly faster rate. The number of inflammatory cells and blood vessels decreased gradually in both groups, with these values being lower in the HA group at each time point but not significantly so. Immunohistochemical examination of the repaired tissue revealed strong staining with anti-chondroitin sulfate proteoglycan antibody in the HA group 2 weeks after the first HA administration. The staining gradually became reduced, with the rate of reduction being faster in the HA group than in the control group. The stimulation of chondroitin sulfate proteoglycan production and the faster reduction of it in the HA group suggests that HA facilitated tissue repair and inhibited the formation of scar tissue.     

Periradicular healing in response to Diaket root-end filling material with and without tricalcium phosphate

The healing of the periradicular tissues was evaluated when the polyvinyl resin Diaket with and without tricalcium phosphate was used as surgical root-end filling material. Non-surgical root canal treatment was performed on 56 mandibular premolar roots in mongrel dogs. Following root-end resection, root-end cavity preparations were filled with Diaket, the comparative material, or Diaket in combination with tricalcium phosphate, the experimental material. Postsurgically, healing of the tissues adjacent to the filling materials and in the surrounding surgical site were evaluated at 30 and 60 days. There was virtually no statistically significant difference between the experimental and comparative group at or within the 30- or 60-day period with regard to inflammation, connective tissue formation, root-end encapsulation, cementum formation, or bone apposition. Findings suggest that cementogenesis occurred over both materials. The overall healing of the periradicular tissues was favourable.     

Comparative effects of plateletderived growth factor-BB and insulin-like growth factor-I, individually and in combination, on periodontal regeneration in Macaca fascicularis

Platelet-derived growth factor (PDGF) and insulin-like growth factor I (IGF-I) in combination have previously been shown to enhance periodontal regeneration. The objective of this study was to further characterize the biological effects of this combination of growth factors in non-human primates and compare the effects to those of each growth factor individually. Ligature-induced periodontitis was initiated in 10 cynomolgus monkeys. After periodontal lesions were established, surgery was performed, and either a methylcellulose gel vehicle or vehicle containing 10 μg each of either PDGF-BB, IGF-I or both PDGF-BB and IGF-I was applied to exposed root surfaces. Biopsies were taken 4 and 12 wk after treatment and the extent of periodontal regeneration was assessed by histomorphometry. At both 4 and 12 wk vehicle-treated lesions generally revealed minimal osseous defect fill (ODF) (8.5±2.1% and 14.5±5.7%, respectively) and new attachment (NA) (34.1±5.2% and 26.6±10.5%, respectively). IGF-I treatment did not significantly alter healing compared to vehicle in any parameter at both 4 and 12 wk. PDGFBB-treated sites exhibited significant (p<0.05) regeneration of NA (69.6±12.0%) at 12 wk; trends for PDGF-BB treatment effect were also observed in other parameters at 4 and 12 wk. although these increases were not statistically significant. Treatment with PDGF-BB/IGF-I resulted in 21.6±5.1 % and 42.5±8.3% ODF at 4 and 12 wk, respectively, and 64.1±7.7% and 74.6±7.4% NA at 4 and 12 wk, respectively (all significantly greater than vehicle, p<0.05). The results from this study demonstrated that: 1) IGF-1 alone at the dose tested did not significantly alter periodontal wound healing; 2) PDGF-BB alone significantly stimulated NA, with trends of effect on other parameters; and 3) the PDGF-BB/IGF-I combination resulted in significant increases in NA and ODF above vehicle at both 4 and 12 wk.