Supplemental L-arginine enhances wound healing in diabetic rats

L-arginine has been shown to enhance wound strength and collagen deposition in rodents and humans. Diabetes mellitus, which impairs wound healing, is accompanied by a reduction in nitric oxide at the wound site. The amino acid L-arginine is the only substrate for nitric oxide synthesis. We sought to determine whether supplemental L-arginine can restore the impaired wound healing of diabetic rats. Fifty-six male Lewis rats were used in this study, of which twenty-nine rats were rendered diabetic 7 days prior to surgery with intraperitoneal streptozotocin. Twenty-seven untreated rats served as controls. Animals underwent a dorsal skin incision with implantation of polyvinyl-alcohol sponges. Sixteen diabetic and 14 normal rats received 1 g/kg/day of L-arginine by injection, while the remainder received saline injections only. Animals were euthanized 10 days postwounding, and their wounds were analyzed for breaking strength. The wound sponges were assayed for total hydroxyproline and nitrite/nitrate content. Plasma and wound fluid concentrations of L-arginine, ornithine, and citrulline were determined. Wound sponge RNA was extracted and subjected to Northern blot analysis for procollagen I and III. Diabetic wounds had greatly decreased breaking strengths compared with controls. L-arginine significantly enhanced wound breaking strengths in both control (+23%) and diabetic animals (+44%), and also increased wound hydroxyproline levels in both diabetic (+40%) and control animals (+24%) as compared to their saline-treated counterparts. mRNA for procollagen I and III were elevated by L-arginine treatment in both diabetic rats and controls. Treatment with L-arginine significantly increased wound fluid nitrite/nitrate levels in diabetic animals. The data show that the impaired healing of diabetic wounds can be partially corrected by L-arginine supplementation, and that this effect is accompanied by enhanced wound nitric oxide synthesis.     

Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice

Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Interactions of different cells, extracellular matrix proteins and their receptors are involved in wound healing, and are mediated by cytokines and growth factors. Previous studies from our laboratory have shown that curcumin (diferuloylmethane), a natural product obtained from the rhizomes of Curcuma longa, enhanced cutaneous wound healing in rats and guinea pigs. In this study, we have evaluated the efficacy of curcumin treatment by oral and topical applications on impaired wound healing in diabetic rats and genetically diabetic mice using a full thickness cutaneous punch wound model. Wounds of animals treated with curcumin showed earlier re-epithelialization, improved neovascularization, increased migration of various cells including dermal myofibroblasts, fibroblasts, and macrophages into the wound bed, and a higher collagen content. Immunohistochemical localization showed an increase in transforming growth factor-beta1 in curcumin-treated wounds compared to controls. Enhanced transforming growth factor-beta1 mRNA expression in treated wounds was confirmed by in situ hybridization, and laser scan cytometry. A delay in the apoptosis patterns was seen in diabetic wounds compared to curcumin treated wounds as shown by terminal deoxynucleotidyl transferase-mediated deoxyuridyl triphosphate nick end labeling analysis. Curcumin was effective both orally and topically. These results show that curcumin enhanced wound repair in diabetic impaired healing, and could be developed as a pharmacological agent in such clinical settings.     

Nitric oxide enhances experimental wound healing in diabetes

BACKGROUND: Diabetes is characterized by a nitric oxide deficiency at the wound site. This study investigated whether exogenous nitric oxide supplementation with the nitric oxide donor molsidomine (N-ethoxycarbomyl-3-morpholinyl-sidnonimine) could reverse the impaired healing in diabetes. METHODS: Wound healing was studied by creating a dorsal skin incision with subcutaneous polyvinyl alcohol sponge implantation in diabetic and non-diabetic rats. Half of each group was treated with molsidomine. Collagen metabolism was assessed by wound breaking strength, hydroxyproline (OHP) content, RNA expression for collagen type I and III, and matrix metalloproteinase (MMP) 2 activity in wound sponges. Wound fluid, plasma and urinary nitric oxide metabolite levels, and the number of inflammatory cells were assessed. RESULTS: OHP content and wound breaking strength were significantly increased by molsidomine. MMP-2 activity in wound fluid was decreased in diabetes and upregulated by nitric oxide donors. The impaired inflammatory reaction in diabetes was unaffected by nitric oxide donor treatment and ex vivo nitric oxide synthesis was no different between wound macrophages from control and diabetic animals, suggesting that the nitric oxide deficiency in the wound is due to a smaller inflammatory reaction in diabetes. CONCLUSION: The nitric oxide donor molsidomine can at least partially reverse impaired healing associated with diabetes.     

Adipose tissue extract enhances skin wound healing

The main function of adipose tissue has been considered as storage of triglycerides. Adipose tissue was considered harmful for healing extensive and deep burns because of poor circulation and easy liquefaction in wound beds, which offer an excellent culture medium for bacteria. However, these traditional concepts have been challenged with the discovery of the endocrine function of adipose tissue. To investigate the effects of adipose tissue extract on wound healing, we created four 3.0 x 2.5 cm full-thickness wounds on each side of the back of male Wu Zhi Shan minipigs (n=6), for eight wounds in each animal. The wounds were randomly divided to receive normal saline (0.5 mL; controls), adipose tissue extract (1.5 g), basic fibroblast growth factor (50 U/cm(2)), and epidermal growth factor (50 U/cm(2)). Reduction in wound area and wound volume was accelerated with adipose tissue treatment as compared with growth factor or control treatment. The thickness of the regenerated epidermis and the number of new vascular nets were markedly increased in adipose tissue-treated wounds. Biopsy of adipose tissue-treated wounds showed enhanced expression of proliferation cell nuclear antigen (PCNA) and Factor VIII-related antigen, which indicated active cell differentiation and proliferation. In vitro study in rat tissue showed adipose tissue extracts stimulating skin growth. Bacteriology results showed no significant differences in amount or type of bacteria, whatever the treatment. These results may challenge the traditional concept that adipose tissue plays a negative role in wound healing and may offer direct evidence for encouraging the retention of adipose tissue in autologous skin grafting for skin wounds.     

Exogenous CLASP2 protein treatment enhances wound healing in vitro and in vivo

Proliferative and migratory abilities of fibroblasts are essential for wound healing at the skin surface. Cytoplasmic linker‐associated protein‐2 (CLASP2) was originally found to interact with cytoplasmic linker protein (CLIP)‐170. CLASP2 plays an important role in microtubule stabilization and the microtubule‐stabilizing activity of CLASP2 depends on its interactions with end binding (EB)‐1 and CLIP‐170. Although the microtubule‐stabilizing role of CLASP2 is well established, the effects of CLASP2 on the migration and proliferation of fibroblasts remain unclear in the context of wound healing. Therefore, we tested the utilization of CLASP2 as a directly applied protein drug to improve wound healing by promoting the migration of effector cells, including skin fibroblasts, to the site of repair or injury using an in vivo excisional wound mouse model and in vitro Hs27 skin fibroblast model. Epidermal growth factor, which is a recognized contributor to cell proliferation and migration, was used as positive control. In vitro and in vivo, CLASP2 treatment significantly enhanced cell migration and accelerated wound closure. Furthermore, in vivo, the CLASP2‐treated animal group displayed enhanced epidermal repair and collagen deposition. Next, we studied the mechanism of CLASP2 for wound healing. Increasing the abundance of intracellular free CLASP2 in skin fibroblasts by supplying exogenous CLASP2 seemed to stabilize microtubules through an interaction between CLASP2 and CLIP‐170, as well as EB1. Exogenous CLASP2 also showed direct binding with IQGAP1, increasing both cyclic adenosine monophosphate activity and phosphorylation of glycogen synthase kinase 3β, which in turn reinstated the binding between free CLASP2 and IQGAP1. In summary, exogenous CLASP2 increased Hs27 skin fibroblast migration by interacting with IQGAP1 and other cytoskeletal linker proteins, such as CLIP‐170 and EB1. Our results strongly suggest that CLASP2 can be developed in wound healing drugs for skin repair and/or regenerating cosmetic products.     

Epidermal growth factor‐containing wound closure enhances wound healing in non‐diabetic and diabetic rats

Background: This study was designed to elucidate the in vivo efficacy of epidermal growth factor (EGF) on wound healing in non diabetic and diabetic rats. Methods: Ninety‐six male Wistar‐Albino rats were randomly divided into six groups. Saline‐moistened gauze, pure gelatin or EGF in gelatin‐microsphere dressings were used in a dermal excision model in both normal and streptomycin‐induced diabetic rats. Wound healing was evaluated on day 7 and 14. Reduction in wound area, hydroxypyroline content and tensile strength of the wound were evaluated in each rat. Tissue samples taken from the wounds were examined histopathologically for reepithelialisation, cellular infiltration, number of fibroblasts, granulation and neovascularisation. Results: On day 7, the use of EGF‐containing dressing was observed to reduce the wound area better when compared with the other dressings tested. This effect was significant in normal rats rather than diabetic rats. The difference in reduction of wound area did not persist on day 14. No significant effect on hydroxyproline content of the wound was found with EGF‐containing dressing in either normal or diabetic rats. There was a statistically significant increase in tensile strength values of EGF‐applied non diabetic rats over the 14 day period. An increase in tensile strength was prominent in also EGF‐applied diabetic rats on day 14. Histological examination revealed higher histopathologic scores in EGF‐applied diabetic and non diabetic rats. Conclusion: These findings implicate that use of EGF in gelatin‐microsphere dressings improves wound healing both in normal and diabetic rats.     

Cyclosporine A impairs wound healing in rats

Cellular immune responses may play an important role in the early inflammatory and cellular phases of wound healing. Cyclosporine A (CSA), a new immunosuppressive agent, impairs cellular immunity and T-cell-dependent humoral immunity. Therefore, the effect of CSA-induced immunosuppression in a rat wound-healing model was studied. Sprague-Dawley rats underwent a standardized skin incision and subcutaneous implantation of sterile polyvinyl alcohol sponges. CSA was dissolved in olive oil and given by gavage to one group of animals at a total dose of 125 mg/kg/10 days. The control group received an equivalent volume of olive oil. Ten-day-old wounds were weaker in CSA-treated animals, both in the fresh state (282 +/- 19 g vs 380 +/- 27 g, P less than 0.01), and after formalin fixation (1111 +/- 74 g vs 1419 +/- 57 g, P less than 0.01). In addition, CSA-treated rats accumulated significantly less hydroxyproline in the wound sponge granuloma, an index of reparative collagen deposition. The impairment in wound healing occurred without differences in body weight gain or organ weights. There was a profound immunosuppression in the animals receiving CSA as determined by thymic lymphocyte blastogenesis in response to Con A and PHA. These findings suggest that immunosuppression in otherwise healthy animals impairs wound healing.     

Arginine enhances wound healing and lymphocyte immune responses in humans

Arginine has been shown to enhance wound healing and T-cell-mediated immune function in rodents. In this study the effect of oral arginine supplementation on human collagen synthesis and T-cell function was studied in 36 healthy, nonsmoking human volunteers. While volunteers were under local anesthesia, a 5 cm segment of expanded polytetrafluoroethylene tubing (1 mm outer diameter, 90 mu pore size) was inserted subcutaneously into the right deltoid region. The volunteers were then randomized into three groups that were given the following substances: (1) daily supplements of 30 gm arginine hydrochloride (24.8 gm free arginine); (2) 30 gm arginine aspartate (17 gm free arginine) daily; or (3) placebo. The supplements were given orally for 2 weeks; dietary intake was not controlled. Mitogenic responses of peripheral blood lymphocytes to phytohemagglutinin and concanavalin A were assayed at the start of study and at 1 and 2 weeks after supplementation. At 2 weeks the catheters were removed, and the amount of hydroxyproline was determined as an index of new collagen synthesis and deposition. Arginine supplementation significantly enhanced the amount of collagen deposited into a standardized wound as assessed by the amount of hydroxyproline present (10.1 +/- 2.32 nmol/cm graft in controls vs 17.57 +/- 2.16 nmol/cm in the arginine aspartate group, [p = 0.028] and vs 23.85 +/- 2.16 nmol/cm in the arginine hydrochloride group [p less than 0.001]). In parallel, arginine supplementation at both doses increased lymphocyte mitogenesis in response to phytohemagglutinin and concanavalin A. The data suggest that arginine may be of clinical benefit in improving wound healing and immune responses.     

Tacrolimus enhances colon anastomotic healing in rats

Tacrolimus inhibits T-cell function and neutrophil chemotaxis during inflammation. We hypothesized that tacrolimus would enhance healing of a rat colon anastomosis by reducing the inflammatory response. Fifty-five male Sprague Dawley rats, 230-260 g body weight, underwent identical surgical manipulation consisting of a single-layer, inverted colon anastomosis and the implantation of osmotic pumps subcutaneously in the left flank area. The animals were randomly assigned to receive tacrolimus, at a dose of 0.01, 0.1, or 1.0 mg/kg/day, or only the control solvent solution. The animals were euthanized 4 days after surgery. Colon-bursting pressure (mmHg), anastomotic collagen content ( micro g hydroxyproline/mg wet tissue), and anastomotic type IV collagenase activity (mU/mg protein) were measured. Tacrolimus significantly increased colon-bursting pressure at all doses used (146 +/- 9, 158 +/- 10, 151 +/- 6 mmHg; 0.01, 0.1, and 1.0 mg/kg/day, respectively) vs. control (119 +/- 7 mmHg, p < 0.01). There was no effect on collagen accumulation except at a dose of 0.01 mg/kg/day, which significantly decreased anastomotic collagen content (p < 0.05). Tacrolimus at a dose of 0.01 mg/kg/day increased anastomotic collagenase activity, which was not changed by treatment with the higher doses. Microscopic examination revealed the preservation of the multilayered structure, including the mucosal muscle, a thickened submucosa, and the proper muscle of the anastomotic site in the tacrolimus-treated groups. These data suggest that tacrolimus enhances wound strength during acute anastomotic healing despite a reduction in collagen content.     

Substance P enhances EPC mobilization for accelerated wound healing

Wound healing is essential for the survival and tissue homeostasis of unicellular and multicellular organisms. The current study demonstrated that the neuropeptide substance P (SP) accelerated the wound healing process, particularly in the skin. Subcutaneous treatment of SP accelerated wound closing, increased the population of α‐smooth muscle actin positive myofibroblasts, and increased extracellular matrix deposition at the wound site. Moreover, SP treatment enhances angiogenesis without a local increase in the expression levels of vascular endothelial growth factor and stromal cell‐derived factor‐1. Importantly, SP treatment increased both the population of circulating endothelial progenitor cells in the peripheral blood and in CD31 positive cells in Matrigel plugs. The tube forming potential of endothelial cells was also enhanced by SP treatment. The results suggested that the subcutaneous injection of SP accelerated the wound healing in the skin via better reconstitution of blood vessels, which possibly followed an increase in the systemic mobilization of endothelial progenitor cells and a more effective assembly of endothelial cells into tubes.     

The effect of interleukin-2 administration on wound healing in adriamycin-treated rats

Adriamycin (doxorubicin hydrochloride), an effective chemotherapeutic drug, is also a potent inhibitor of wound healing. Conversely, certain polypeptide growth factors are capable of stimulating fibroblasts to secrete collagen, thus enhancing wound healing. The purpose of this study was to determine if interleukin-2 (IL-2), a T-cell growth factor, could reverse the wound healing deficit caused by Adriamycin. Adriamycin treatment caused a significant decrease in wound-breaking strength (P less than 0.005). IL-2 administration increased wound-breaking strength in Adriamycin-treated animals (2126 g vs 1549 g, P less than 0.005). In control animals, IL-2 did not increase wound-breaking strength significantly (2708 g vs 2608 g, P greater than 0.1). Histologically, wounds from Adriamycin-treated animals were less cellular, demonstrated less collagen in the dermis, and a lesser degree of capillary ingrowth. The number of fibroblasts in the dermal layer was increased in animals receiving IL-2. Control rats gained an average of 1.4% of their original body weight, while Adriamycin-treated rats lost an average of 19% of their original body weight (P less than 0.0005). IL-2 administration did not influence weight loss or gain. Hematologically, animals receiving Adriamycin had lower hemoglobin and hematocrit values and higher platelet counts. There were no differences in total white blood cell counts; however, animals receiving Adriamycin showed a predominance of polymorphonuclear leukocytes and a relative decrease in lymphocytes. Animals receiving IL-2 demonstrated a significant eosinophilia. (1) Adriamycin impairs normal wound healing. (2) Interleukin-2 administration improves the wound healing impairment caused by Adriamycin. (3) Interleukin-2 appears to increase infiltration of inflammatory cells, fibroblasts, and capillaries into the wound, which may account for the observed increase in wound breaking strength.     

Ozonated sesame oil enhances cutaneous wound healing in SKH1 mice

Ozone is well recognized as a bactericidal agent and its beneficial effect on wound healing could be a consequence of this property. Because ozone itself does not penetrate the cells but immediately reacts with polyunsaturated fatty acids, its effects should be the results of oxidative reaction. For this reason, ozonated oils could be a way to deliver ozone messengers to the skin. This paper evaluated the therapeutic effects of three different grades of ozonated sesame oil in acute cutaneous wounds made in the skin of SKH1 mice. Specifically, wound closure rate, histological parameters, and the level of key proteins such as vascular endothelial growth factors and cyclin D1 have been analyzed in relation to the peroxide level present in the ozonated oil. Treatment with moderately ozonated sesame oil—expressed as peroxide value about 1,500)—has a faster wound closure rate in the first 7 days than treatment with oil containing either lower or higher peroxide value, and even with controls. Moreover, under the same treatment, an earlier and higher response of cells involved in wound repair, a higher angiogenesis, as well as an enhanced vascular endothelial growth factors and cyclin D1 expression were observed. The present study shows the validity of ozonated sesame oil in cutaneous wound healing and emphasizes the importance of the ozonation grade.     

Laser photostimulation accelerates wound healing in diabetic rats

In this study, we examined the hypothesis that laser photostimulation can facilitate healing of impaired wounds in experimental diabetes using a rat model. Diabetes was induced in male rats by streptozotocin injection and two 6 mm diameter circular wounds were created on either side of the spine. The left wound of each animal was treated with a 632.8 nm He:Ne laser at a dose of 1.0 J/cm2 for five days a week until the wounds closed (three weeks). Measurements of the biomechanical properties of the laser-treated wounds indicated there was a marginal increase in maximum load (16%), stress (16%), strain (27%), energy absorption (47%) and toughness (84%) compared to control wounds of diabetic rats. Biochemical assays revealed that the amount of total collagen was significantly increased in laser treated wounds (274 +/- 8.7 microg) over the control wounds (230 +/- 8.4 microg). Sequential extractions of collagen from healing wounds showed that laser treated wounds had significantly greater concentrations of neutral salt soluble (15%) and insoluble collagen (16%) than control wounds, suggesting accelerated collagen production in laser treated wounds. There was an appreciable decrease in pepsin soluble collagen (19%) in laser treated wounds over control wounds, indicating higher resistance to proteolytic digestion. In conclusion, the biomechanical and biochemical results collectively suggest that laser photostimulation promotes the tissue repair process by accelerating collagen production and promoting overall connective tissue stability in healing wounds of diabetic rats.     

Bioactive interleukin-8 is expressed in wounds and enhances wound healing

BACKGROUND: Wound healing is a sequential biological process that involves the integration of chemotaxis of neutrophils, mitosis and migration of keratinocytes, and remodeling of the scar, all of which are regulated by specific soluble mediators. To modulate wound healing specific mediators have to be identified and functionally characterized. Therefore we addressed this study on the polymorphonuclear leukocyte (PMN) attractant interleukin-8 (IL-8) and its function in epidermal wound healing. MATERIALS AND METHODS: Peptide purification, bioassays for PMN chemotaxis, and sequential IL-8 measurements were performed on human wound fluid from burn blisters and skin graft donor sites. Histology for IL-8 immunoreactivity was included. In vitro human keratinocytes were assayed for proliferation, migration, and integrin expression after IL-8 treatment. Wounding experiments with topical IL-8 were performed in a chimeric mouse model. RESULTS: IL-8 was found to be the major bioactive chemoattractant for PMNs in human blister and skin graft donor site wound fluids (mean levels ranging from 173 ng/ml Postoperative Day (POD) 1 to 2130 ng/ml (POD 5)). Released intracellular epidermal IL-8 immunoreactivity at the wound edge was considered as an immediate source of IL-8 while NH(2)-terminal analysis revealed the 77-amino-acid residue form as a second source of IL-8 possibly PMN derived. In vitro experiments on the effect of recombinant human (rh) IL-8 on keratinocyte proliferation revealed a rise in cell number (4.8-fold, ED(50) = 0.6 ng/ml), which was accompanied by an increase in cells in S phase and overexpression of the integrin subunit alpha6. In vivo topically applied IL-8 (1 microg/ml) on human skin grafts in a chimeric mouse model enhanced reepithelialization in IL-8 treated animals over controls due to elevated numbers of mitotic keratinocytes. Wound contraction was significantly diminished by topical IL-8. CONCLUSIONS: These results indicate the sequential function of endogenous IL-8 in all phases of human wound healing. Topical IL-8 may be useful in impaired wound healing.     

Supplemental l-arginine enhances wound healing following trauma/hemorrhagic shock

To determine whether parenteral L-arginine supplementation enhances the impaired wound healing of rats subjected to trauma/hemorrhagic shock. Impaired wound healing after trauma and shock has been documented experimentally and clinically. L-arginine has been shown to enhance wound strength and collagen synthesis in rodents and humans. Its efficacy under conditions of impaired wound healing is less well defined. Forty-eight male Lewis rats were used in this study. Using a well-defined model, 24 rats underwent trauma/hemorrhagic shock before wounding. Twenty-four untreated rats served as controls. All animals underwent a dorsal skin incision with implantation of polyvinyl-alcohol sponges. Half of the animals in each group were assigned to receive 1 g/kg/day of L-arginine by intraperitoneal injection in three divided doses, while the other half received saline injections only. Animals were sacrificed 10 days postwounding, and wound-breaking strength (WBS) and wound sponge total hydroxyproline (OHP) and nitrite/nitrate (NO(x)) content were determined. Wound sponge RNA was collected and subjected to Northern blot analysis for procollagens I and III. Trauma/hemorrhage greatly decreased WBS with a concomitant diminution in collagen (OHP) deposition. L-arginine significantly enhanced WBS (19%) and increased OHP (21%) levels in control animals as well as in rats subjected to trauma/hemorrhage (WBS +29%, OHP 40%) compared with their saline-treated counterparts. Procollagen I and III mRNA levels were elevated by L-arginine treatment in both trauma/hemorrhage and control rats. Arginine treatment had no effect on wound fluid and plasma NO(x). The data demonstrate that the impaired healing subsequent to trauma/hemorrhage can be greatly alleviated by L-arginine supplementation.     

Simultaneous irrigation and negative pressure wound therapy enhances wound healing and reduces wound bioburden in a porcine model

Infected foot wounds are one of the most common reasons for hospitalization and amputation among persons with diabetes. The objective of the study was to investigate a new wound therapy system that employs negative pressure wound therapy (NPWT) with simultaneous irrigation therapy. For this study, we used a porcine model with full‐thickness excisional wounds, inoculated with Pseudomonas aeruginosa. Wounds were treated for 21 days of therapy with either NPWT, NPWT with simultaneous irrigation therapy using normal saline or polyhexanide biguanide (PHMB) at low or high flow rates, or control. Data show that NPWT with either irrigation condition improved wound healing rates over control‐treated wounds, yet did not differ from NPWT alone. NPWT improved bioburden over control‐treated wounds. NPWT with simultaneous irrigation further reduced bioburden over control and NPWT‐treated wounds; however, flow rate did not affect these outcomes. Together, these data show that NPWT with simultaneous irrigation therapy with either normal saline or PHMB has a positive effect on bioburden in a porcine model, which may translate clinically to improved wound healing outcomes.     

Lentiviral-mediated BMP-2 gene transfer enhances healing of segmental femoral defects in rats

The objective of the present study was to assess the ability of bone marrow cells expressing BMP-2 created via lentiviral gene transfer to heal a critical sized femoral defect in a rat model. Femoral defects in Lewis rats were implanted with 5x10(6) rat bone marrow stromal cells (RBMSC) transduced with a lentiviral vector containing either the BMP-2 gene (Group I), the enhanced green fluorescent protein (LV-GFP) gene (Group IV), or RBMSC alone (Group V). We also included femoral defects that were treated with BMP-2-producing RBMSC transduced with lentivirus, 8 weeks after infection (Group III), and a group with 1x10(6) RBMSC transduced with a lentiviral vector with the BMP-2 gene (Group II). All defects (10/10) treated in Group I healed at 8 weeks compared with none of the femora in the control groups (Groups IV and V). In Group II, only one out of 10 femora healed. In Group III, 5 out of 10 femora healed. Significantly higher amounts of in vitro BMP-2 protein production were detected in Groups I, II, and III when compared to that of the control groups (p<0.05). Histomorphometric analysis revealed significantly greater total bone volume in defects in Group I and III when compared to control specimens (p<0.003). Biomechanical testing revealed no significant differences in the healed defects in Groups I and III when compared to intact, nonoperated femora with respect to peak torque and torque to failure. Our results indicate that BMP-2-producing RBMSC created through lentiviral gene transfer have the capability of inducing long-term protein production in vitro and producing substantial new bone formation in vivo.     

去神经支配对大鼠创面愈合的影响

目的通过制备去神经支配大鼠创面模型,观察去神经大鼠创面愈合率、创面血管和皮肤增殖改变情况,为去神经创面Ⅹ合机制提供理论依据。方法分离并切断SD大鼠胸9～腰1右侧脊神经,造模后在背部对称制作两个直径为1.0cm的圆形创面,分别观察两侧创面愈合时间、创面大体和组织形态学、创面细胞增殖活性、创面修复过程中血管再生情况,并对数据进行统计学分析。结果实验组愈合时间在4周,对照组为3周;实验组创面上皮化速度慢于对照组;实验组愈合表皮层较薄,上皮细胞大小不一;愈合时真皮和表皮层细胞增殖活跃,2～4周时实验组增殖活性低于对照组(P0.05);创面微血管主要分布于真皮层,密度随Ⅹ合时间增加,但2～4周实验组表现较对照组弱(P0.05)。结论去神经后皮肤创面细胞增殖低下,愈合时间延长,血管再生现象受到抑制。