功能敷料的“伤口湿润环境愈合”理论与实践

简述了传统敷料理论和敷料类别,结合对伤口的分类与愈合机理,详细阐述了"伤口湿润环境愈合"理论的发展历程与机理与优势,比较分析了数种功能敷料在结构和功能设计中应用"伤口湿润环境愈合"理论的实践及能测试与评价方法。经分析认为,"伤口湿润环境愈合"理论有利于伤口愈合和临床护理,已成为伤口,尤其是慢性伤口护理的新准则,该理论对功能敷料的设计研发具有指导意义。

读音“告”的两个本字谈

重庆话常用"告"来表"尝试"意义,也通常把"伤口癒合"叫做"告口"。经过考察发现,表"尝试"义的本字应当是"较",而并非人们所写字形"告";表"伤口癒合"意义的方言词,不应写成"告口"而该写作"交口"。口语中表"尝试"义和"伤口癒合"义的"gào",当与"告"这个字形无任何关联。

Epithelial restitution and wound healing in inflammatory bowel disease

Inflammatory bowel disease is characterized by a chronic inflammation of the intestinal mucosa. The mucosal epithelium of the alimentary tract constitutes a key element of the mucosal barrier to a broad spectrum of deleterious substances present within the intestinal lumen including bacterial microorganisms, various dietary factors, gastrointestinal secretory products and drugs. In addition, this mucosal barrier can be disturbed in the course of various intestinal disorders including inflammatory bowel diseases. Fortunately, the integrity of the gastrointestinal surface epithelium is rapidly reestablished even after extensive destruction. Rapid resealing of the epithelial barrier following injuries is accomplished by a process termed epithelial restitution, followed by more delayed mechanisms of epithelial wound healing including increased epithelial cell proliferation and epithelial cell differentiation. Restitution of the intestinal surface epithelium is modulated by a range of highly divergent factors among them a broad spectrum of structurally distinct regulatory peptides, variously described as growth factors or cytokines. Several regulatory peptide factors act from the basolateral site of the epithelial surface and enhance epithelial cell restitution through TGF-13-dependent pathways. In contrast, members of the trefoil factor family （TFF peptides） appear to stimulate epithelial restitution in conjunction with mucin glycoproteins through a TGF-13-independent mechanism from the apical site of the intestinal epithelium. In addition, a number of other peptide molecules like extracellular matrix factors and blood clotting factors and also non- peptide molecules including phospholipids~ short-chain fatty acids （SCFA）, adenine nucleotides, trace elements and pharmacological agents modulate intestinal epithelial repair mechanisms. Repeated damage and injury of the intestinal surface are key features of various intestinal disorders including inflammatory bowel diseases and require constant repair of the epithelium. Enhancement of intestinal repair mechanisms by regulatory peptides or other modulatory factors may provide future approaches for the treatment of diseases that are characterized by injuries of the epithelial surface.

Traditional Chinese surgical treatment for anal fistulae with secondary tracks and abscess

AIM:To evaluate the efficacy and safety of traditional Chinese surgical treatment for anal fistulae with secondary tracks and abscess.METHODS:Sixty patients with intersphincteric or transsphincteric anal fistulas with secondary tracks and abscess were randomly divided into study group [suture dragging combined with pad compression(SDPC)] and control group [fistulotomy(FSLT)].In the SDPC group,the internal opening was excised and incisions at external openings were made for drainage.Silk sutures were put through every two incisions and knotted in loose state.The suture dragging process started from the first day after surgery and the pad compression process started when all sutures were removed as wound tissue became fresh and without discharge.In the FSLT group,the internal opening and all tracts were laid open and cleaned by normal saline postoperatively till all wounds healed.The time of healing,postoperative pain score(visual analogue scale),recurrence rate,patient satisfaction,incontinence evaluation and anorectal manometry before and after the treatment were examined.RESULTS:There were no significant differences between the two groups regarding age,gender and fistulae type.The time of healing was significantly shorter(24.33 d in SDPC vs 31.57 d in FSLT,P < 0.01) and the patient satisfaction score at 1 mo postoperative followup was significantly higher in the SDPC group(4.07 in SDPC vs 3.37 in FSLT,P < 0.05).The mean maximal postoperative pain scores were 5.83 ± 2.5 in SDPC vs 6.37 ± 2.33 in FSLT and the recurrence rates were 3.33 in SDPC vs 0 in FSLT.None of the patients in the two groups experienced liquid and solid fecal incontinence and lifestyle alteration postoperatively.The Wexner score after treatment of intersphincter fistulae were 0.17 ± 0.41 in SDPC vs 0.40 ± 0.89 in FSLT and transsphincter fistulae were 0.13 ± 0.45 in SDPC vs 0.56 ± 1.35 in FSLT.The maximal squeeze pressure and resting pressure declined after treatment in both groups.The maximal anal squeeze pressures after treatment were reduced(23.17 ± 3.73 Kpa in SDPC vs 22.74 ± 4.47 Kpa in FSLT) and so did the resting pressures(12.36 ± 2.15 Kpa in SDPC vs 11.71 ± 1.87 Kpa in FSLT),but there were neither significant differences between the two groups and nor significant differences before or after treatment.CONCLUSION:Traditional Chinese surgical treatment SDPC for anal fistulae with secondary tracks and abscess is safe,effective and less invasive.

Continuous wound infusion of local anaesthetic agents following colorectal surgery:Systematic review and meta-analysis

AIM:To provide a specifi c review and meta-analysis of the available evidence for continuous wound infusion of local anaesthetic agents following midline laparoto-my for major colorectal surgery. METHODS: Medline, Embase, trial registries, conference proceedings and article reference lists were searched to identify randomised, controlled trials of continuous wound infusion of local anaesthetic agents following colorectal surgery. The primary outcomes were opioid consumption, pain visual analogue scores (VASs), return to bowel function and length of hospital stay. Weighted mean difference were calculated for continuous outcomes. RESULTS: Five trials containing 542 laparotomy wounds were eligible for inclusion. There was a sig- nificant decrease in post-operative pain VAS at rest on day 3 (weighted mean difference: -0.43; 95% CI: -0.81 to -0.04; P = 0.03) but not on post-operative day 1 and 2. Local anaesthetic infusion was associated with a signifi cant reduction in pain VAS on movement on all three post-operative days (day 1 weighted mean difference: -1.14; 95% CI: -2.24 to -0.041; P = 0.04, day 2 weighted mean difference: -0.97, 95% CI: -1.91to -0.029; P = 0.04, day 3 weighted mean difference: -0.61; 95% CI: 1.01 to -0.20; P = 0.0038). Local an- aesthetic wound infusion was associated with a signifi - cant decrease in total opioid consumption (weighted mean difference: -40.13; 95% CI: -76.74 to -3.53; P = 0.03). There was no signifi cant decrease in length of stay (weighted mean difference: -20.87; 95% CI: -46.96 to 5.21; P = 0.12) or return of bowel function (weighted mean difference: -9.40; 95% CI: -33.98 to 15.17; P = 0.45). CONCLUSION: The results of this systematic re- view and meta-analysis suggest that local anaesthetic wound infusion following laparotomy for major color- ectal surgery is a promising technique but do not pro- vide conclusive evidence of benefi t. Further research is required including cost-effectiveness analysis.

Analgesis and Wound Healing Effect of Chitosan and Carboxymethyl Chitosan on Scalded Rats

Analgesis and wound healing effect of chitosan and carboxymethyl chitosan on scalded rats were investigated. A II degree scald model was established in rats, which was subsequently treated with chitosan and carboxymethyl chitosan solution, respectively. The concentration of bradykinin and 5-hydroxytryptophan was detected by assaying enzyme-linked immunosorbent. Healing condition was observed and pathological sections were made to determine the healing effect of chitosan and carboxymethyl chitosan. Results showed that the concentration of bradykinin and 5-hydroxytryptophan peaked at the third hour post-wound in all groups, while the concentration of hydroxyproline peaked at the seventh day post-wound in both chitosan and carboxymethyl chitosan group. The concentration of bradykinin and 5-hydroxytryptophan of carboxymethyl chitosan group was significantly lower than that of control(P < 0.05), while that of chitosan group was similar to that of control(P > 0.05). These findings indicated that carboxymethyl chitosan reduced the concentration of algogenic substances, resulting in analgesia. During the whole recovery process, the hydroxyproline concentration in chitosan and carboxymethyl chitosan group on day 3 and 7 was significantly higher than that of control(P < 0.01); however the significance of such a highness decreased on day 14(P < 0.05). These findings indicated that chitosan and carboxymethyl chitosan accelerated tissue repair. Meanwhile, chitosan performed better in healing than carboxymethyl chitosan in both decrustation and healing time. In conclusion, carboxymethyl chitosan showed significant analgesis and wound-healing promotion effect, but chitosan only showed wound-healing promotion effect.

Ephrin-B reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells

AIM： Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells. METHODS： Upon stimulation of ephrin-B pathways in IEC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase （FAK） activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy. RESULTS： Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes. Furthermore, we show that the expression of repair- related genes is also accompanied by activation of the ERKI/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution. CONCLUSION： Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.

Ultrastructural view of colon anastomosis under propolis effect by transmission electron microscopy

AIM： To evaluate the effect of propolis administration on the healing of colon anastomosis with light and transmission electron microscopes. METHODS： Forty-eight Wistar-AIbino female rats were divided into two groups and had colon resection and anastomosis. In group Ⅰ, rats were fed with standard rat chow pre- and postoperatively. The rats in group Ⅱ were fed with standard rat chow and began receiving oral supplementation of propolis 100 mg/kg per day beginning 7 d before the operation and continued until they were sacrificed. Rats were sacrificed 1, 3, 7 and 14 d after operation, and anastomotic bursting pressures measured. After the resection of anastomotic segments, histopathological examination was performed with light and transmission electron microscopes by two blinded histologists and photographed. RESULTS： The colonic bursting pressures of the propolis group were statistically significantly better than the control group. UItrastructural histopathological analysis of the colon anastomosis revealed that propotis accelerated the phases of the healing process and stimulated mature granulation tissue formation and collagen synthesis of fibroblasts. CONCLUSION： Bursting pressure measurements and ultra structural histopathological evaluation showed that administration of propolis accelerated the healing of colon anastomosis following surgical excision.

Impact of remote ischemic preconditioning on wound healing in small bowel anastomoses

AIM： To investigate the influence of remote ischemic preconditioning （RIPC） on anastomotic integrity. METHODS： Sixty male Wistar rats were randomized to six groups. The control group （n = 10） had an end- to-end ileal anastomosis without RIPC. The preconditioned groups （n = 34） varied in time of ischemia and time of reperfusion. One group received the amino acid L-arginine before constructing the anastomosis （n = 9）. On postoperative day 4, the rats were re-laparotomized, and bursting pressure, hydroxyproline concentration, intra-abdominal adhesions, and a histological score concerning the mucosat ischemic injury were collected. The data are given as median （range）.RESULTS： On postoperative day 4, median bursting pressure was 124 mmHg （60-146 mmHg） in the control group. The experimental groups did not show a statistically significant difference （P 〉 0.05）. Regarding the hydroxyproline concentration, we did not find any significant variation in the experimental groups. We detected significantly less mucosal injury in the RIPC groups. Furthermore, we assessed more extensive intra-abdominal adhesions in the preconditioned groups than in the control group. CONCLUSION： RIPC directly before performing small bowel anastomosis does not affect anastomotic stability in the early period, as seen in ischemic preconditioning.

Effectiveness of fire needle combining with moist healing dressing to promote the growth of granulation tissue in chronic wounds:A case report

In this case study,we analyzed the wound-healing process of a patient with a chronic wound who underwent fire needle treatment,and we tracked the coverage of granulation tissue and decrease of slough and exudate.An 85-year-old man had repeated right shoulder and back pain,itching,and skin festering for more than 1.5 years.A fire needle was administered combined with moist dressing once every 5 days to promote wound healing.After six rounds of fire needle treatment,granulation tissue formed over the surface of the wound base,the depth of the wound had become shallow,and the wound area was reduced.No complications occurred during the intervention.Fire needle therapy combined with a moist wound-healing dressing can be an effective alternative approach in managing chronic wounds.

Effects of chitosan-TPP nanoparticles on hepatic tissue after severe bleeding

Recently, chitosan nanoparticles have been an attractive biomaterial for their unique properties. Chitosan nanoparticles are mainly used as drug delivers. However, they are seldom used in wound healing after severe bleeding. In the present paper, chitosan nanoparticles with an average size of 60.2 nm were prepared through ionic gelation and characterized by X-ray diffraction and FT-infrared spectrometry. A new animal model of severe bleeding was made to evaluate its effects on wound healing besides hemostasis. The results showed that it can achieve well hemostatic effects and also induce wound healing after severe bleeding. Blood cells can be absorbed by chitosan nanoparticles and the bleeding is treated. Furthermore, the chitosan nanoparticles sustains longer than other materials in wound healing. At the 15th day after operation, the chitosan nanoparticles with the size of 58.3 nm can still be seen in the new-regenerated hepatic tissue. It can induce the formation of a clear granulation around the wound site. Through histological observation, we find out that chitosan-TPP nanoparticles can induce wound healing through migration of the inflammatory cells and synthesis of collagen. So, chitosan nanoparticles show us both hemostasis and the ability of wound healing for parenchymal organs.

Rebamipide promotes healing of colonic ulceration through enhanced epithelial restitution

AIM:To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro.METHODS:Acute colitis was induced with trinitrobenzene sulfonic acid(TNBS)in male Wistar rats.Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration.The distal colon was removed to evaluate the various parameters of inflammation.Moreover,wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial(RIE)cells treated with rebamipide.RESULTS:Intracolonic administration of rebamipide accelerated TNBSinduced ulcer healing.Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide.The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signalregulated kinase(ERK)and activation of Rho kinase.CONCLUSION:Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells,via ERK activation.Rebamipide might be a novel therapeutic approach for inflammatory bowel disease.

A study on the expressions and the correlation of TGF-β1 and α-SMA in healing process of bile duct trauma

Objective: To explore the formation mechanism of benign biliary stricture. Methods: A model of trauma of common bile duct was established in 28 dogs and then repaired. The anasomosis tissues were taken on the 1st week, 3rd week and the 3rd month, 6th month respectively after operation and examined by using light microscopy and elec-tromicroscopy. Macrophage, TGF-p, and a-SMA were studied immunohistochemically. Results: The mucosal epithelium of common bile duct restored poorly, chronic inflammation lasted for a long time, fibroblasts proliferated actively, extracellular matrix overdeposited; and myofibroblasts functioned actively and existed during the whole healing process. Immunohistochemical test showed a high expression of macrophage, TGF-β1 and a-SMA during healing process lasting a long duration. Macrophages were found in the lamina propria under mucosa, TGF-β1 in the granulation tissue, fibroblasts and endothelial cells of blood vesssels, while a-SMA in the myofiroblasts and smooth muscle tissue. Conclusion: The healing of bile duct is in the mode of overhealing. Myofibroblast is the main cause for contracture of scar and stricture of bile duct. The high expression of macrophage, TGF-β1 and a-SMA is closely related to active proliferation of fibroblasts, extracelluar matrix overdeposition and scar contracture of bile duct.

In Silico Screening of Potential Drug with Antileishmanial Activty and Validation of their Activity by in Vitro and in Vivo Studies

The research on discovery and development of new treatments for cutaneous leishmaniasis has been declared as priority. Using bioinformatics approaches, this study aimed to identify antileishmanial activity in drugs that are currently used as anti-inflammatory and wound healing by such anti-Leishmania activity was validated by in vitro and in vivo assays. In silico analysis identified 153 compounds from which 87 were selected by data mining of DrugBank database, 22 and 44 were detected by PASS （http：//pass.cribi.unipd.it） and BLAST （http：//blast.ncbi.nlm.nih. gov/） alignment, respectively. The majority of identified drugs are used as skin protector, anti-acne, anti-ulcerative （wound healer） or anti-inflammatory and few of them had specific antileishmanial activity. The efficacy as antileishmanial was validated in vitro in 12/23 tested compounds and in all seven compounds that were evaluated in in vivo assays. Notably, this is the first report of antileishmanial activity for adapalene. In conclusion, bioinformatics tools not only can help to reduce time and cost of the drug discovery process but also may increase the chance that candidates identified in silico which have a validated antileishmanial activity by combining different biological properties.

Effect of radical surgery combined with pre- or postoperative radiotherapy in treatment of resectable rectal cancer

Objective： This study was done to compare between the effect of preoperative radiotherapy and postoperative radiotherapy in treatment of resectable rectal carcinoma. The primary endpoints are local recurrence rate, overall survival （OS） and disease free survival （DFS）. The secondary endpoints are to evaluate down-staging, treatment toxicity, and ability to do sphincter preservation, aiming at choosing the optimal treatment modality. Methods： This study included 100 patients with resectable rectal carcinoma who presented to Surgical Gastro Entrology Center and Clinical Oncology and Nuclear Medicine Department, Mansoura University during the period between January 2007 and September 2009. The included patients were randomized in two groups; group h 50 patients received preoperative radiotherapy and group Ih 50 patients received post- operative radiotherapy. Concurrent 5-fluorouracil-based chemotherapy was given to all patients. Two major types of surgery were done： abdomino-perineal resection with a permanent colostomy and low anterior resection with colorectal or coloanal anastomosis. Results： Preoperative radiotherapy resulted in pathologic complete response in 3 patients. T down-staging occurred in 18 out of 50 patients （36%） with statistically significant difference （P = 0.008）. N down-staging occurred in 10 out of 24 patients. Sphincter preservation was more in group I. Delayed wound healing was the most common postoperative complication in group I with no significant difference. After a median follow up of 18 months, local recurrence rate and distant metastasis were higher in group I1. The 2-year disease free survival was 72% and 60% in group I and II respectively with no statistically significant difference between both groups. Conclusion： This study concluded that preoperative radiotherapy is better than postoperative radiotherapy as regard local control, sphincter preservation with higher disease free survival and overall survival. No difference in treatment toxicity between both groups.

Z-plasty for uterus-to-abdominal-wall fistula

Objective:Uterus-to-abdominal-wall fistula is a very rare complication after uterine-incision delivery over the last decades.It can even lead to death.Mainly,the fistula occurs when big tension and critical infection exist within the incision of uterus and abdominal wall.Methods:The authors described the clinical presentation,pathology of uterus-to-abdominal-wall fistula,and reported their experience in 6 cases who underwent Z-plasty operation for this rare complication from January 1998 to January 2008.Results:All flaps survived completely and all the wounds in abdominal walls healed very well.The six cases were followed up for 1 to 5 years,and no fistula recurrence occurred.Conclusion:Z-plasty technique is a very simple and efficient approach to repair uterus to abdominal fistula after uterine-incision delivery.

Canine Extremity Wound Treatment with Chitosan Extracted from Shrimp Shells： A Case Report

The aim of this case report was to demonstrate the effectivity of chitosan as topical agent on the treatment of severely infected canine extremity wound. The dog was hit by a bus and presented severe friction wounds accompanying with bilateral hip and extremity fractures. Local and generalized infections were observed on the post operational period. The dog was unresponsive to the standard therapeutic protocols and health status was getting worsened. The regenerative sutures did not hold the tissues because of the infection and the tissue eruption. Chitosan samples were extracted from shrimp shell wastes. The milled form of chitosan was topically used to treat the open and heavily mix infected wound areas located at skin and rear extremities accompanying with fever and Canine coronavirus diarrhea. It was decided to use the chitosan as a bio barrier and anti-bio affect over the damaged and erupted tissues. Macroscopic fmdings indicated chitosan promoted the natural blood clotting and absorbed the inflammation fluid. Microscopic findings indicated the infiltration of polymorph nuclear leukocytes （PMN） accelerated with the topical use of chitosan in the early phase of wound healing. The wound healing was observed daily. This veterinary practice wound treatment result indicated that chitosan is effective to medicate topically the canine open and mix infected wounds with bacteria and viruses and promotes the granulomatosis in four weeks period.

Effects of 2,5-Norbornadiene （NBD） on Physiological and Biochemical Responses of Fresh-cut Winter Squash

Ethylene is one of the most important plant hormones that regulate physiological responses, maturity and senescence of postharvest fruits and vegetables. The determination of its role in the wound-healing response of fruits and vegetables is helpful in understanding the wound responses. 2,5-Norbornadiene （NBD）, inhibitor ethylene binding were used to determine the effect of ethylene action on wound-induced response of fresh-cut winter squash, a kind of vegetables known to produce ethylene markedly after cutting. The effect of NBD on the physiological and biochemical changes of fresh-cut winter squash was investigated in this experiment. The results showed that NBD had great effects on physio-biochemical metabolism of fresh-cut winter squash. Ethylene production was inhibited significantly by NBD. NBD also had an inhibition effect on polyphenol oxidase （PPO）, peroxidase （POD） and phenylalanine ammonia lyase （PAL） activity. The effect of NBD on lipoxygenase （LOX） activity and superoxide dismutase （SOD） was not obvious. NBD treated sample showed a more rapid increase in catalase （CAT） activity, which may help in healing the damage of the tissue. These information are important in understanding the fundamental biology of wound response and in the development of new technology to hasten wound-healing and, thereby, to minimize costly wound-related problems in fresh-cut industry.

Sensitivity of Some Biological Objects to Repetitive Submicrosecond Microwave Pulses

The effect of repetitive pulsed microwaves （10 GHz, pulse duration of 100-300 ns, pulse repetition rate of 4-25 pulse per second, peak power density of 0.04-3.5 kW/cm^2） on mastocytoma P815, Ehrlich carcinoma, normal spleen cells and wound healing was investigated. It was found that short-time irradiation with an intensity of 0.9-1.5 kW/cm^2 inhibited proliferation of tumor cells in vitro, whereas at same time it contributes to proliferation of normal spleen cells in vitro. The repetitive pulsed microwaves with an intensity of 0.04-1.5 kW/cm^2 stimulated healing of skin wounds and ulcerations in mice. The effects showed a dependence on the pulse repetition rate and irradiation intensity.

Expression of positive and negative regulators of cell cycle during wound healing

OBJECTIVE: To detect the expression of cell cycle positive regulators cyclin D(1), cyclin E, CDK(2), CDK(4) and negative regulators p21(cip1), p27(kip1), p16(ink4a) and p15(ink4b) during wound healing in rats. METHODS: Open wounds of full-thickness skin, diameter 1.8 cm, on rat backs were used as the wound model. Wound tissues were harvested on postwounding days 3, 5, 7, 9, 11, 14, 21 and 30. Ki67 expression in granulation tissue was detected by immunohistochemical assay. The patterns of the expression of cyclin D(1), cyclin E, CDK(2), CDK(4) and p21(cip1), p27(kip1), p16(ink4a), p15(ink4b) were detected by Western blot. RESULTS: Cell proliferation in granulation tissue took place predominantly within the first week after injury, with the proliferation peak occurring at postwounding day 5. There were no dramatic variations in the expression of cyclin D(1), CDK(2) and CDK(4) during wound healing. Up-regulated cyclin E was maintained from day 3 to 11 after injury, and then was down-regulated. No expression of p16(ink4a) and p15(ink4b) was found. p21(cip1) was expressed only from day 7 to 14, with peak expression observed on day 9. Constitutive p27(kip1) was expressed throughout wound healing with low levels in the proliferating period of day 3 to 5 and with increased levels in the post-mitotic and remodeling stage. The expression of p21(cip1) and p27(kip1) showed an inverse gradient to that of Ki67. CONCLUSION: p21(cip1) and p27(kip1) play a supervising role in preventing the hyperproliferative tendency in tissue repair.