甲硝唑对大鼠深Ⅱ度烧伤创面愈合的影响

目的研究甲硝唑对大鼠深度烧伤创面愈合的影响。方法20只SD大鼠,随机分为两组,制成20%体表面积深度烫伤,实验组采用甲硝唑180mg/kg灌胃,对照组采用相同剂量1%羧甲基纤维素钠灌胃,每天1次直至创面愈合,观察创面愈合天数,光镜观察肉芽组织及胶原纤维生长情况,电镜观察成纤维细胞生长情况。结果大鼠全部存活。实验组创面愈合所需时间与对照组相比差异有显著性(P<0.05)。伤后7d及14d光镜观察发现实验组肉芽组织及胶原纤维生长优于对照组,14d时实验组创面再上皮化的进程优于对照组。伤后14d时电镜观察发现实验组成纤维细胞生长优于对照组。结论口服甲硝唑可以加速烧伤创面的愈合。     

Exosome loaded genipin crosslinked hydrogel facilitates full thickness cutaneous wound healing in rat animal model

Full thickness cutaneous wound therapy and regeneration remains a critical challenge in clinical therapeutics. Recent reports have suggested that mesenchymal stem cells exosomes therapy is a promising technology with great potential to efficiently promote tissue regeneration. Multifunctional hydrogel composed of both synthetic materials and natural materials is an effective carrier for exosomes loading. Herein, we constructed a biodegradable, dual-sensitive hydrogel encapsulated human umbilical cord-mesenchymal stem cells (hUCMSCs) derived exosomes to facilitate wound healing and skin regeneration process. The materials characterization, exosomes identification, and in vivo full-thickness cutaneous wound healing effect of the hydrogels were performed and evaluated. The in vivo results demonstrated the exosomes loaded hydrogel had significantly improved wound closure, re-epithelialization rates, collagen deposition in the wound sites. More skin appendages were observed in exosomes loaded hydrogel treated wound, indicating the potential to achieve complete skin regeneration. This study provides a new access for complete cutaneous wound regeneration via a genipin crosslinked dual-sensitive hydrogel loading hUCMSCs derived exosomes.     

Curcumin‐loaded poly(ε‐caprolactone) nanofibres: Diabetic wound dressing with anti‐oxidant and anti‐inflammatory properties

• 1 Curcumin is a naturally occurring poly‐phenolic compound with a broad range of favourable biological functions, including anti‐cancer, anti‐oxidant and anti‐inflammatory activities. The low bioavailability and in vivo stability of curcumin require the development of suitable carrier vehicles to deliver the molecule in a sustained manner at therapeutic levels.
• 2 In the present study, we investigated the feasibility and potential of poly(caprolactone) (PCL) nanofibres as a delivery vehicle for curcumin for wound healing applications. By optimizing the electrospinning parameters, bead‐free curcumin‐loaded PCL nanofibres were developed.
• 3 The fibres showed sustained release of curcumin for 72 h and could be made to deliver a dose much lower than the reported cytotoxic concentration while remaining bioactive. Human foreskin fibroblast cells (HFF‐1) showed more than 70% viability on curcumin‐loaded nanofibres.
• 4 The anti‐oxidant activity of curcumin‐loaded nanofibres was demonstrated using an oxygen radical absorbance capacity (ORAC) assay and by the ability of the fibres to maintain the viability of HFF‐1 cells under conditions of oxidative stress.
• 5 The curcumin‐loaded nanofibres also reduced inflammatory induction, as evidenced by low levels of interleukin‐6 release from mouse monocyte–macrophages seeded onto the fibres following stimulation by Escherichia coli‐derived lipopolysaccharide.
• 6 The in vivo wound healing capability of the curcumin loaded PCL nanofibres was demonstrated by an increased rate of wound closure in a streptozotocin‐induced diabetic mice model.
• 7 These results demonstrate that the curcumin‐loaded PCL nanofibre matrix is bioactive and has potential as a wound dressing with anti‐oxidant and anti‐inflammatory properties.

     

Carbohydrate‐derived Fulvic acid (CHD‐FA) inhibits Carrageenan‐induced inflammation and enhances wound healing: efficacy and Toxicity study in rats

The objectives of this study were to evaluate the safety and anti‐inflammatory and wound‐healing characteristics of carbohydrate‐derived fulvic acid (CHD‐FA) in rats. CHD‐FA (≥100 mg/kg p.o.) effectively reduced carrageenan‐induced paw edema in rats, which was comparable to 10 mg/kg p.o. indomethacin. Topical application of CHD‐FA, formulated to contain 1.75% active product in a cetomicrogol cream at pH 1.98, compared favorably with fusidic acid cream (10 mg/g) in accelerating the healing of excised wounds infected with Staphylococcus aureus. No signs of toxicity were observed in rats during the 6‐day acute and 6‐month chronic treatment with CHD‐FA (100 mg/kg p.o.). Topical application of CHD‐FA, formulated in UEA cream and applied to the right ears of mice at 400 mg/g body weight on days 1 and 7–38, produced no adverse events. No signs of toxicity were observed in the teratogenicity study, in which CHD‐FA was administered at 100 mg/kg p.o. to pregnant female mice 3 days before fertilization to 14 days of pregnancy. In conclusion, CHD‐FA is a safe compound with anti‐inflammatory and wound‐healing properties and merits further evaluation in the treatment of patients suffering from similar conditions. Drug Dev Res 73: 18–23, 2012. © 2011 Wiley Periodicals, Inc.     

愈伤灵膏对烫伤的治疗作用及其作用机理初步研究

目的对民间秘方愈伤灵膏的烧烫伤治疗作用及其作用机理进行初步研究以验证其疗效并初步探讨其作用机理。方法大鼠烫伤模型、角叉菜胶致大鼠足肿胀模型、二甲苯致小鼠耳肿胀及小鼠烫伤部位组织含水量测定。结果愈伤灵膏可明显促进烫伤大鼠脱痂、缩短愈合时间 ,并能显著抑制角叉菜胶致大鼠足肿胀、二甲苯致小鼠耳肿胀及降低小鼠烫伤部位的组织含水量。结论愈伤灵膏对烫伤具有一定的治疗作用 ,其作用机理可能与烫伤初期减少渗出有关。     

The reduction in inflammation and impairment in wound healing by using strontium chloride hexahydrate

Background: Numerous growth factors, cytokine, mitogen and chemotactic factors are involved in wound healing. Even though inflammation is important for the stimulation of proliferative phase, excessive inflammation also causes impairment in wound healing. Strontium salts suppress keratinocyte-induced TNF-alpha and interleukin-1 and interleukin-6 in in vitro cultures. This study was conducted to determine the effects of administration of topical strontium chloride hexahydrate on wound healing through TNF-alpha and TGF-beta in surgical wound healing model of in-vivo rat skin.

Material and methods: Twenty-four rats were used in the study. After approximately 2?cm cutaneous–subcutaneous incision was horizontally carried out on the mid-neckline of the rats, the incision was again closed using 2.0 vicryl. The rats were assigned into three groups including eight rats in each group. Placebo emollient ointment and also the ointments, which were containing 5% and 10% strontium chloride hexahydrate and were prepared at the same base with placebo ointment, were administered to the groups by a blind executor twice a day for a week. At the end of seventh day, the rats were sacrificed and cutaneous and subcutaneous tissue of their wound site was resected for histopathological examination. Scoring of histopathological wound healing and scoring of tissue TNF-alpha and TGF-beta level with immunohistochemical staining were performed.

Results: The groups, to which both 5% and 10% strontium chloride hexahydrate was administered, had lower immunohistochemical TNF-alpha levels and histopathological wound scores compared to controls, which was statistically significant (p?Conclusion: Strontium chloride hexahydrate can lead to impairment in wound healing by suppressing inflammation through TNF-alpha.     

复方环丙沙星烧伤凝胶对实验性创面愈合作用的影响

目的:观察复方环丙沙星烧伤凝胶对动物实验性烫伤创面愈合的影响.方法:通过对创面羟脯氨酸的测定及分别对家兔、豚鼠Ⅱ°Ⅲ°烫伤模型的愈合时间进行观察研究.结果:复方环丙沙星烧伤凝胶外涂对家兔、小鼠、豚鼠烧伤创面的愈合有显著促进作用.结论:复方环丙沙星烧伤凝胶能显著缩短家兔、豚鼠烫伤创面的愈合时间.     

Evaluation of wound healing effect of chitosan-based gel formulation containing vitexin

Acute or chronic wounds are one of the most common health problems worldwide and medicinal drugs or traditional remedies are often used in wound healing. Further studies regarding wound treatment are rapidly continuing. Vitexin is a phenolic compound, which is found in many medicinal plants, has different pharmacological effects such as anti-inflammatory, analgesic and antioxidant. In the present study, it is aimed to investigate the wound healing effect of formulation prepared as chitosan-based gel with vitexin in vivo and in vitro. Cytotoxicity and wound healing assays were used for in vitro and excisional wound model is used for in vivo studies. Extracted tissues from wound area were histologically examined. Wound healing process was monitored on 7, 14 and 21st days. When wound construction was evaluated, chitosan-based gel formulation containing vitexin demonstrated significant effect compared to control group. Histological examinations demonstrated that skin regeneration was promoted by vitexin formulation. Significant cell proliferation was observed with vitexin/chitosan dispersion in the wound healing assay performed with NIH 3T3 and HaCaT cells. In conclusion, our test substance chitosan-based gel formulation containing vitexin significantly accelerated wound healing both in vivo and in vitro.     

Collagen‐based wound dressing for doxycycline delivery: in‐vivo evaluation in an infected excisional wound model in rats

Objectives A novel collagen‐based dressing consisting of 2,3‐dihydroxybenzoic‐acid‐modified gelatin microspheres loaded with doxycycline has previously been reported to address both infection and matrix degradation. In the present study the potential benefits of the dressing were investigated in an excisional wound model in rats challenged with Pseudomonas aeruginosa. Methods A full‐thick excisional wound (1.5 times 1.5 cm) was created on the dorsum of the rats and infection induced by injecting 10⁵ colony‐forming units (CFU) of P. aeruginosa. The healing pattern was assessed from wound reduction, matrix metalloprotease (MMP) levels, CFU reduction and histological and biochemical analysis. Key findings The treated group exhibited complete healing by day 15, compared with day 24 in the control group. Early subsidence of infection (99.9% by day 9) resulted in faster epidermal resurfacing and fibroplasias, whereas the microbial load exceeded 10³ CFU even on day 15 in the control group and caused severe inflammation. Biochemical analysis showed that the expression of both collagen and hexosamine was significantly increased in the treated group. Gelatin zymography revealed prolonged expression of MMPs 2, 8 and 9 in the control group compared with the treated group. Conclusions The study indicates that the developed dressing attenuated both infection and metalloprotease levels, and may therefore have potential application in wound healing.     

Electrospun multifunctional nanofibrous mats loaded with bioactive anemoside B4 for accelerated wound healing in diabetic mice

With the worldwide prevalence of diabetes and considering the complicated microenvironment of diabetic wounds, the design and development of innovative multifunctional wound dressing materials are much wanted for the treatment of hard-to-heal wounds in diabetic patients. In the present study, anti-inflammatory ingredients loaded with nanofibrous wound dressing materials were manufactured by a promising blend-electrospinning strategy, and their capability for treating the diabetic wound was also systematically explored. A polymer blend consisting of Chitosan (CS) and polyvinyl alcohol (PVA) was electrospun into CS-PVA nanofibrous mats as control groups. In the meanwhile, a bioactive ingredient of Chinese medicine Pulsatilla, anemoside B4(ANE), with different contents were loaded into the electrospinning solution to construct CS-PVA-ANE nanofibrous mats. The developed CS-PVA-ANE wound dressing materials exhibited multifunctional properties including prominent water absorption, biomimetic elastic mechanical properties, and sustained ANE releasing behavior, as well as outstanding hemostatic properties. The in vitro studies showed that the CS-PVA-ANE nanofiber mats could significantly suppress lipopolysaccharide (LPS)-stimulated differentiation of pro-inflammatory (M1) macrophage subsets, and notably reduce the reactive oxygen species (ROS) generation, as well as obviously decrease inflammatory cytokine release. The in vivo animal studies showed that the CS-PVA-ANE nanofiber mats promoted the healing of diabetic wounds by significantly enhancing wound closure rates, accelerating excellent angiogenesis, promoting re-epithelization and collagen matrix deposition throughout all stages of wound healing. The present study demonstrated that CS-PVA-ANE nanofiber mats could effectively shorten the wound-healing time by inhibiting inflammatory activity, which makes them promising candidates for the treatment of hard-to-heal wounds caused by diabetes.     

利伐沙班在股骨转子问骨折围术期中的作用及对切口愈合的影响

目的观察利伐沙班在老年股骨转子间骨折患者闭合复位内固定术围术期中的作用及对术后切口愈合的影响,并评估术后至切口拆线前使用该药物的安全性及可行性。方法选取2011年6月～2012年12月大连医科大学附属第一医院创伤骨科146例股骨转子间骨折患者．随机分为3组,分别采用物理疗法、皮下注射低分子量肝素、13服利伐沙班治疗。记录术后切口渗血量,平均拆线时间,12天内拆线数,不良切口发生率,术前和术后1、3、7d的胛及AHT值,下肢深静脉血栓（DVT）和肺栓塞（PE）发生率,并进行比较。结果物理疗法组切口渗血量为（48．2±5．0）ml,低分子量肝素组为（47．1±5．4）ml,利伐沙班组为（49．6±4．8）ml,差异无统计学意义（P〉0．05）。物理疗法组平均拆线时间为（13．0±2．0）d,低分子量肝素组为（12．5±2．5）d,利伐沙班组为（13．0±1．5）d,差异无统计学意义（P〉0．05）。物理治疗组12天内拆线数为48例（98．0％）,低分子量肝素组为46例（95．8％）,利伐沙班组为39例（79．6％）,差异无统计学意义（D0．05）。物理治疗组不良切口发生率为2．0％,低分子量肝素组为4．2％,利伐沙班组为20．4％。差异有统计学意义（P〈0．05）。3组患者术前和术后1、3、7d的PT及APTT值比较,差异无统计学意义（P〉0．05）。物理疗法组DVT发生率为44．9％,低分子量肝素组为18．8％,利伐沙班组为6．1％,差异有统计学意义（P〈0．05）。物理疗法组PE发生率为20．4％,低分子量肝素组为10．4％,利伐沙班组为2．0％,差异有统计学意义（P〈0．05）。结论利伐沙班虽然会导致股骨转子间骨折患者术后切口愈合时间延长,但其不会引起凝血象改变,且在预防DVT及PE方面,效果优于物理疗法及低分子量肝素。     

Epigallocatechin‐3‐gallate augments therapeutic effects of mesenchymal stem cells in skin wound healing

In non‐healing wounds, mesenchymal stem cell (MSC)‐based therapies have the potential to activate a series of coordinated cellular processes, including angiogenesis, inflammation, cell migration, proliferation and epidermal terminal differentiation. As pro‐inflammatory reactions play indispensable roles in initiating wound repair, sustained and prolonged inflammation exhibit detrimental effects on skin wound closure. We investigated the feasibility of using an antioxidant agent epigallocatechin‐3‐gallate (EGCG), along with MSCs, to improve wound repair through their immunomodulatory actions. In a rat model of wound healing, a single dose of EGCG at 10 mg/kg increased the efficiency of MSC‐induced skin wound closure. Twenty days after the wound induction, MSC treatment significantly enhanced the epidermal thickness, which was further increased by EGCG administration. Consistently, the highest extent of growth factors upregulation for neovascularization induction was seen in the animals treated by both MSCs and EGCG, associated with a potent anti‐scarring effect throughout the healing process. Finally, expression levels of pro‐inflammatory cytokines, such as tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β) and IL‐6, in the wound area were reduced by MSCs, and this reduction was further potentiated by EGCG co‐administration. EGCG, together with MSCs, can promote skin wound healing likely through their combinational effects in modulating chronic inflammation.     

The effects of topical (gel) astemizole and terfenadine on wound healing

Objective:

To develop topical gel preparations of astemizole and terfenadine and to investigate the actions of the gels on the healing of incision and excision wounds in male albino rats.

Materials and Methods:

Gels containing 1% astemizole, with varying concentrations of carbopol 934 (polymer), were prepared. Similarly, 1% terfenadine gels were made. The formulations were evaluated for release rate and stability. Incision and excision wounds were inflicted on male albino rats under ketamine anesthesia, taking aseptic precautions. The animals were divided into two groups. They were given a topical application of either astemizole or terfenadine gel, at a dose of 100 mg per wound, once daily, for 10 days in the case of incision wounds and till the time of complete closure in the case of excision wounds. On the 11^th day, breaking strength of the incision wound was measured. In the excision wound model, wound closure rate, epithelization time, scar features and hydroxyproline content of scar tissue were studied from the day of wounding till the day of the scab falling off, with no residual raw area.

Results:

Gels prepared using 0.8% carbopol 934 and 1% of drug in gel base were found to be stable. The gels of astemizole and terfenadine significantly (P < 0.05) promoted the phases of healing such as collagenation (in incision wounds), wound contraction and epithelization (in excision wounds).

Conclusion:

The gels of astemizole and terfenadine might play an important role in wound management program.     

八味紫草烧伤膏的镇痛和创面愈合实验研究

目的考察自制八味紫草烧伤膏对烧伤后创面修复和镇痛的影响。方法运用小鼠热板法和大鼠皮肤烫伤后局部给药法,考察八味紫草烧伤膏对创面的镇痛作用和促进愈合作用。结果八味紫草烧伤膏能够明显提高小鼠痛阈值,促进大鼠Ⅱ度烧伤模型坏死组织脱落和皮肤再生进程。结论八味紫草烧伤膏具有促进创面愈合和镇痛的作用。     

TGF-β对创伤愈合与瘢痕形成的影响及中药的干预作用

目的对近年来转化生长因子β(transforming growth factorβ,TGF-β)在创伤愈合和瘢痕形成过程中的作用及中药对其的干预作用做以综述。方法查阅大量国内外文献,分析、总结TGF-β在创伤愈合和瘢痕形成过程中的研究现状和研究前景。结果 TGF-β在调节细胞增殖、分化、迁移、黏附及细胞外基质形成、胚胎发育、骨的重建等方面发挥重要作用。TGF-β在创伤愈合和瘢痕形成过程中是关键的活性分子,TGF-β的3种亚型在创伤愈合过程中存在时间和空间上的差异性,且功能各异。中药由于其成分复杂,在创伤修复及瘢痕形成过程中显示不同的作用特点,对TGF-β的干预作用也呈现不同特点。结论 TGF-β在创伤愈合和瘢痕形成过程中发挥着重要的作用,具体作用机制有待进一步阐明。因此探讨TGF-β在创伤愈合和瘢痕形成过程中的作用机制及中药对其的干预作用具有重要意义。