富血小板血浆与贫血小板血浆治疗中华眼镜蛇细胞毒素致小鼠皮肤溃疡的效果比较

目的 比较富血小板血浆(PRP)与贫血小板血浆(PPP)治疗中华眼镜蛇细胞毒素致小鼠皮肤溃疡的效果。方法 将中华眼镜蛇细胞毒素造模成功的30只中小鼠随机分为对照组(n=10)、PRP组(n=10)、PPP组(n=10),造模后第9天各组分别给予单纯生理盐水、PRP、PPP治疗,比较3组小鼠皮肤溃疡面积、溃疡创面愈合率、创面面积差绝对值与HE染色的病理改变。结果 低速组的PRP、PPP符合工作浓度标准。PRP凝胶、PPP凝胶治疗小鼠溃疡愈合时间可缩短3 d。PRP组与PPP组创面愈合率及3 d内面积差绝对值均大于对照组(均P<0.05)。镜下见PRP凝胶、PPP凝胶可减少炎症细胞浸润,促进小鼠上皮细胞再上皮化等病理改变。结论 PRP凝胶、PPP凝胶均可促进中华眼镜蛇伤溃疡皮肤修复,缩短愈合时间。     

组织工程复合皮肤应用于皮肤缺损创面的临床疗效观察

目的:临床观察组织工程复合皮肤对烧伤整形后需植皮患者的供皮区缺损创面的有效性及安全性。方法:试验选取不同临床中心烧伤整形后需植皮患者,在供皮区部分创面作为试验区应用组织工程复合皮肤覆盖,邻近创面采用盐水纱布替代作为对照区,应用后按常规方法包扎固定。临床试验时间为6个月,治疗期间观察统计患者的创面反应,愈合时间及愈合情况;对组织工程复合皮肤改善创面愈合质量及安全性进行临床评估。根据创面试验组和对照组的创面愈合时间,应用SPSS统计软件对数据进行方差齐性检验,根据检验结果分别进行独立样本t或t’检验。结果:试验共收集有效病例19例。临床观察显示应用后试验区创面无明显免疫排斥及炎性反应,患者自述疼痛明显减轻,试验区创面愈合时间与对照区相比缩短8d,统计学分析有显著性差异。愈后随访部分患者试验区愈合质量好于对照区,应用后患者疼痛、瘢痕形成等不良反应明显减少。结论:结果表明组织工程复合皮肤作为活型皮肤替代物用于医源性皮肤缺损的修复,这为促进供皮区的创面愈合提供了切实可行的方法。     

创面生物活性玻璃修复材料促进家猪创面愈合的实验研究

目的:观察创面生物活性玻璃修复材料对家猪皮肤创面的促愈合作用。方法:选择14头家猪,随机分成7组,每组2头,在每头猪的脊柱两旁制造3个4×4cm的全层皮肤缺损的创面模型,每头猪6个创面又分成实验组和空白对照组,于试验后每天观察创面愈合情况,第1、3、7、14、21、28、35天图像分析计算创面愈合率,并同时取创面组织行组织学染色,观察各组材料对家猪皮肤全层缺损创面愈合的影响。结果:在涂材料的实验组和空白对照组创面愈合时间分别是23.19±1.27d、29.52±1.54d两组组间比较,具有统计学意义(P<0.05);实验组的创面愈合率在各时间段均高于空白对照组,差异有统计学意义(P<0.05);组织学观察实验组的上皮化程度、表皮生长、成纤维细胞、毛细血管数量均好于空白对照组。结论:创面生物活性玻璃修复材料对家猪皮肤创面愈合具有促进作用,可作为一种新型的促愈合覆盖材料进一步研究。     

富血小板浓缩物在鼓膜穿孔中的疗效及研究进展

鼓膜穿孔(tympanic membrane perforation,TMP)是耳鼻咽喉科常见的疾病。急性TMP多数能自愈,而慢性TMP现主要使用手术治疗,然而现有手术治疗方法均存在缺陷,例如需要全麻、费用较高、技巧复杂等,故探究更佳的治疗方法显得尤为重要。富血小板浓缩物主要包括富血小板血浆(platelet-rich plasma,PRP)和富血小板纤维(platelet-rich fibrin,PRF),其富含生长因子和白细胞,故可有效促进组织再生,并降低感染发生率。以往作为新型修复材料,PRP和PRF已被应用于耳科治疗TMP,并被证实在TMP愈合中具有良好的疗效。因此,该文将对近年来血小板浓缩物用于TMP修复的文献进行回顾与总结分析。     

使用富血小板血浆对下肢慢性创面缺损的临床研究分析

目的:研究和探讨使用富血小板血浆(platelet-rich plasma, PRP)在人体下肢慢性创面缺损中的治疗作用,并试图寻找更佳的治疗皮肤慢性缺损的治疗方式。方法:对2016.03-2017.03一年以来在我科治疗,明确诊断为慢性创面缺损的,经纳入和排除标准筛选的共计16名患者进行分析。将其分为实验组(8人)与对照组(8人)。实验组通过对静脉血(肘部)进行抽取离心来制备富血小板血浆并加以覆盖。对照组则使用重组人表皮生长因子进行替代。两组患者均以7天为一疗程,进行换药和更换辅料。比较两组患者的创面愈合情况并比较其血液指标。结果:实验组患者在治疗后1周时观察创面,发现创面无明显渗出及感染征象,其面积缩小约1/4。对照组在1周后进行观察,发现1例有感染可能,给予再次清创并使用抗生素后辅料包扎。其余患者创面肉芽生长可,面积缩小约1/6。在治疗2周后再次进行观察,发现实验组患者创面面积缩小约2/3。而对照组患者面积缩小约1/4。在治疗后3周时,实验组所有患者创面已基本愈合85%以上。在延迟治疗1-2周后该组患者全部愈合。对照组患者在治疗3周后有两例患者愈合面积在50%以上。给予继续使用该治疗方法。剩余6例患者接受外科治疗(VSD+植皮/皮瓣)。实验组患者在各治疗观察点皮肤愈合情况较对照组均有显著改善(P0.05)。两组所有患者均未出现严重并发症。结论:对于下肢慢性创面,使用富血小板血浆进行治疗,能够有效的促进创面愈合,减少手术及外科治疗的风险,降低治疗费用,且相对安全,具有非常重要的临床推广价值。     

局部应用生长因子促进颅骨缝牵引成骨的实验研究

目的:研究局部应用富血小板血浆及人重组BMP2对颅缝牵引成骨的作用,并用Micro-CT进行影像学评价,为进一步了解生长因子对颅缝的改建作用提供依据。方法:将30只雄性6周龄的新西兰白兔随机分为3组:(0)对照组,(1)富血小板血浆组(PRP),(2)富血小板血浆结合10μg rhBMP-2组(PRP/rhBMP-2)。用镍钛牵开弹簧给予兔矢状颅骨缝持续200 g等张牵引力牵引33天。牵引结束后,采集所有兔矢状颅骨缝标本行Micro CT精细扫描及三维重建及硬组织切片观察成骨情况。结果:Micro CT重建兔矢状颅骨缝显示,对照组和PRP组的骨缝牵开,骨缝牵开体积比PRP/rhBMP-2凝胶组大(P0.05)。PRP的局部应用不仅促进了骨缝间的新骨形成,而且加速骨缝纤维组织的创伤愈合。PRP/rhBMP-2组牵引后骨缝可见有新骨再生及骨缝融合现象。PRP/rhBMP-2凝胶组平均骨缝融合程度约为颅骨厚度的15.3±9.5%。实验前后PRP/rhBMP-2凝胶组治疗区颅骨平均厚度较对照组和PRP凝胶组有增厚表现(P0.05)。结论:PRP和PRP/rhBMP-2的局部应用都能有效促进骨缝牵引成骨时新骨加速形成。Micro CT显示:PRP凝胶可以诱导骨缝骨形成并加速了骨缝伤口的愈合,缝形态存在;PRP/rhBMP-2组新骨再生导致了骨缝牵引时过早产生了骨缝融合现象,提示今后在骨缝牵引成骨临床应用时需要避免高浓度生长因子在骨缝局部应用而导致的骨缝早闭。     

重组人表皮生长因子在面部瘢痕修复治疗中的应用

目的:分析重组人表皮生长因子(rhEGF)在面部瘢痕修复治疗中的应用价值。方法:选择2013年3月-2016年2月我院收治的80例面部瘢痕患者作为研究对象,按随机数字表法分为对照组与观察组各40例,两组均应用二氧化碳点阵激光进行面部瘢痕修复治疗,观察组术后加用rh EGF敷于皮肤表面,对照组则采用等渗盐水敷于皮肤表面,比较两组治疗不同时间创面愈合率、创面愈合时间及换药时疼痛情况,测定创面愈合后患者瘢痕面积,并评定创面处理后不同时间患者肉芽组织成熟情况、创面愈合后瘢痕面积及不良反应的发生情况。结果:两组术后7 d、术后14 d创面愈合率均显著高于术后3 d(P0.05),观察组术后不同时间创面愈合率均显著高于对照组(P0.05);观察组创面愈合时间短于对照组,其创面愈合后瘢痕面积小于对照组(P0.05);观察组换药时疼痛程度低于对照组,其轻度疼痛所占比例高于对照组(P0.05);观察组术后7 d、14 d肉芽组织成熟分级均高于对照组(P0.05)。两组均未见炎症全身不良反应。结论:re EGF可促进面部瘢痕患者创面修复,缩短创面愈合时间,缩小瘢痕面积,减轻患者换药疼痛程度,促进肉芽组织成熟,且安全性高。     

半导体激光联合全蝎软膏对大鼠糖尿病性皮肤溃疡修复的研究

目的:探讨半导体激光联合全蝎软膏对大鼠糖尿病皮肤溃疡(DSU)的修复作用。方法:24只SPF级Wistar大鼠随机平均分为对照组、模型组、全蝎软膏组和联合组,以腹腔注射链脲佐菌素-皮肤缺损法构建大鼠DSU模型;建模后分别用激光和/或全蝎软膏对DSU大鼠进行治疗,观察用药后3 d、7 d、10 d和14 d的大鼠体重、血糖值及创面肉芽组织愈合情况;随后,分别对创面组织进行H.E染色、免疫组化、ELISA法及western blot检测。结果:建模后的DSU大鼠体重、血糖与对照组比较有统计学差异(P0.05),且成模率为73.33%;各治疗组创面愈合率均高于模型组(P0.05),肉芽组织生长旺盛,毛细血管丰富,炎症反应减轻;ELISA和western blot结果显示,与模型组相比,联合组治疗后组织内血管内皮生长因子(v EGF)显著上升(P0.05)、肿瘤坏死因子α(TNF-α)和Smad 4蛋白水平显著降低(P0.05),治疗效果优于全蝎软膏组。结论:半导体激光联合全蝎软膏可有效促进大鼠DSU创面的愈合,减轻炎症反应并修复血管功能,效果优于全蝎软膏组。     

创面生物活性玻璃修复材料促进家猪创面愈合的实验研究

目的：观察创面生物活性玻璃修复材料对家猪皮肤创面的促愈合作用。方法：选择14头家猪,随机分成7组,每组2头,在每头猪的脊柱两旁制造3个4×4cm的全层皮肤缺损的创面模型,每头猪6个创面又分成实验组和空白对照组,于试验后每天观察创面愈合情况,第1、3、7、14、21、28、35天图像分析计算创面愈合率,并同时取创面组织行组织学染色,观察各组材料对家猪皮肤全层缺损创面愈合的影响。结果：在涂材料的实验组和空白对照组创面愈合时间分别是23.19±1.27d、29.52±1.54d两组组间比较,具有统计学意义（P〈0.05）;实验组的创面愈合率在各时间段均高于空白对照组,差异有统计学意义（P〈0.05）;组织学观察实验组的上皮化程度、表皮生长、成纤维细胞、毛细血管数量均好于空白对照组。结论：创面生物活性玻璃修复材料对家猪皮肤创面愈合具有促进作用,可作为一种新型的促愈合覆盖材料进一步研究。     

皮肤创伤愈合过程中短暂扩增细胞增生及皮肤干细胞迁移

目的研究皮肤疤痕组织形成过程中皮肤干细胞分布、增殖分化迁移特征,初步探讨这些特征与皮肤创伤修复的关系。方法利用眼科显微外科剪对2日龄昆明小鼠背部皮肤进行人工统一造创,定期获取皮肤创面样品,常规病理染色观察创面愈合形态;应用免疫荧光染色法,以细胞转录因子Sox2和角蛋白14抗体分别检测皮肤干细胞的分布及干细胞增殖分化时所形成的短暂扩增细胞,并结合细胞增殖EdU荧光染色初步分析皮肤干细胞的迁移方向。结果创面愈合过程中表皮层中表达Sox2的阳性细胞逐渐连贯,并且发现真皮乳头层中Sox2和角蛋白14同时大量表达,可见致密细胞网和向下凸起的新生毛囊样结构形成。同时,创面愈合初期细胞迁移主要由创面底部开始,向上迁移并填充创面。结论创面愈合过程中,创面底部皮肤干细胞首先开始大量分裂增殖,并向创面迁移,创面上部皮肤干细胞分裂增殖迟于创面底部;迁移的皮肤干细胞以不对称分裂的形式增殖形成大量短暂扩增细胞,并在增厚的疤痕乳头层部位形成毛囊样结构填充皮肤疤痕。     

Combination of an engineered Lactococcus lactis expressing CXCL12 with light-emitting diode yellow light as a treatment for scalded skin in mice

Impaired wound closure is an increasingly crucial clinical challenge. Recently, wound healing has shifted towards innovative treatments that exploit nanotechnology, biomaterials, biologics and phototherapy. Here, we constructed an engineered MG1363-pMG36e-mCXCL12 strain with pMG36e plasmid encoding stromal cell-derived factor 1α (named CXCL12) and evaluated the synergistic effects of light-emitting diode (LED) yellow light and MG1363-pMG36e-mCXCL12 on scald wounds in mice. The results indicated that the combined treatment with LED yellow light with mCXCL12 delivering strain accelerated wound closure, tissue remodelling, re-epithelialization and hair follicle regeneration and inhibited over-inflammation oppositely in the central and surrounding wounds by macroscopic, histopathologic and immunohistochemistry parameters. Furthermore, combination therapy increased the epidermal growth factor and Ki67-positive cells and upregulated beta-catenin (β-catenin), cellular-myelocytomatosis (c-Myc), wingless-type MMTV integration site family member 1 (Wnt1), Jagged 1, neurogenic locus notch homolog protein 1 (Notch 1) and hairy and enhancer of split 1 (Hes 1) protein levels of the Wnt and Notch signalling pathways. It also facilitated collagen fibrogenesis and deposition and improved the activities of hydroxyproline, superoxide dismutase and glutathione peroxidase in scalded granulation tissue, in addition to reducing the inflammatory factors interleukin 1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α). The combined treatment effectively reduced skin pathogens Ralstonia and Acinetobacter to further reduce the risk of infection. Overall, combination of LED yellow light and MG1363-pMG36e-mCXCL12 represents a potential strategy for the treatment of cutaneous wounds.     

Gender Affects Skin Wound Healing in Plasminogen Deficient Mice

The fibrinolytic activity of plasmin plays a fundamental role in resolution of blood clots and clearance of extravascular deposited fibrin in damaged tissues. These vital functions of plasmin are exploited by malignant cells to accelerate tumor growth and facilitate metastases. Mice lacking functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds revealed larger amounts of fibrotic scars in the provisional matrix of plasmin deficient male mice compared to female mice. These fibrotic scars correlated to an obstruction of cell infiltration of the granulation tissue, which is a prerequisite for wound healing. In conclusion, the presented data show that the gender dependent effect of plasmin deficiency is tissue specific and may be secondary to already established differences between genders, such as skin thickness and composition.     

Tissue Engineered Skin Substitutes Created by Laser-Assisted Bioprinting Form Skin-Like Structures in the Dorsal Skin Fold Chamber in Mice

Tissue engineering plays an important role in the production of skin equivalents for the therapy of chronic and especially burn wounds. Actually, there exists no (cellularized) skin equivalent which might be able to satisfactorily mimic native skin. Here, we utilized a laser-assisted bioprinting (LaBP) technique to create a fully cellularized skin substitute. The unique feature of LaBP is the possibility to position different cell types in an exact three-dimensional (3D) spatial pattern. For the creation of the skin substitutes, we positioned fibroblasts and keratinocytes on top of a stabilizing matrix (Matriderm®). These skin constructs were subsequently tested in vivo, employing the dorsal skin fold chamber in nude mice. The transplants were placed into full-thickness skin wounds and were fully connected to the surrounding tissue when explanted after 11 days. The printed keratinocytes formed a multi-layered epidermis with beginning differentiation and stratum corneum. Proliferation of the keratinocytes was mainly detected in the suprabasal layers. In vitro controls, which were cultivated at the air-liquid-interface, also exhibited proliferative cells, but they were rather located in the whole epidermis. E-cadherin as a hint for adherens junctions and therefore tissue formation could be found in the epidermis in vivo as well as in vitro. In both conditions, the printed fibroblasts partly stayed on top of the underlying Matriderm® where they produced collagen, while part of them migrated into the Matriderm®. In the mice, some blood vessels could be found to grow from the wound bed and the wound edges in direction of the printed cells. In conclusion, we could show the successful 3D printing of a cell construct via LaBP and the subsequent tissue formation in vivo. These findings represent the prerequisite for the creation of a complex tissue like skin, consisting of different cell types in an intricate 3D pattern.     

胰腺癌裸鼠皮下异种移植动物模型建立研究

目的:用人体胰腺癌细胞株,建立小鼠胰腺癌细胞株(pGHAM-1)移植性胰腺癌模型,并研究其生物学特性。方法:将pGHAM-1细胞培养后配成1×107/ml,取0.2mL接种于小鼠皮下。于接种后20、30、40天观察肿瘤的生长、转移及腹水量。接种40天后处死动物,解剖取出移植瘤,用游标卡尺测量肿瘤大小,再进行HE染色的组织病理学检查,免疫组织化学检测血管内皮细胞生长因子(VEGF)及肿瘤转移相关蛋白(nm23-H1)的表达。结果:分别于20、30、40天测量肿瘤体积为84.1±21.9 mm3,413.7±208.4 mm3,2187.3±1882.8 mm3,后者与10 d前比较差异均具有统计学意义(P<0.01)。HE染色结果显示肿瘤组织呈条索状或小梁状排列,肿瘤组织与正常组织交界处有少量淋巴细胞浸润,肿瘤组织中血管生成罕见。免疫组织结果显示VEGF和nm23-H1蛋白在肿瘤组织中均呈阴性表达。结论:异位裸鼠人胰腺癌移植瘤模型易复制,时间短,成功率高,为胰腺癌体内研究提供了理想的动物模型。     

Matrix metalloproteinase 9 (MMP-9) is upregulated during scarless wound healing in athymic nude mice

Cutaneous wound healing is associated with migratory and remodeling events that require the action of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Differences in their expressions were observed during scar-forming and scar-free skin wound healing. We previously found that athymic nude mice are exceptional among mature mammals in their ability to heal injured skin scarlessly. The present study was undertaken to determine whether the modulation of MMP-2 and MMP-9 expression during scarless healing in nude mice was different from scar-forming animals. Full thickness skin wounds were made into the back of nude, wild-type controls (C57BL/6J), immunodeficient SCID and Rag, thymectomized neonates and adults, and cyclosporin A treated mice. Post-injured skin tissues were harvested at Day 7 and 24 after injury. Quantitative RT-PCR, Western blot, gelatin zymography and immunohistochemical assays were performed. Our results show that MMP-2 protein was high but similarly expressed in all post-injured animals on Day 7 after injury. Late phase (Day 24) of wound repair was characterized by a decrease in mRNA and protein expression and a decrease in gelatinolytic activity of MMP-2 in all post-injured samples. On the contrary, high (p < 0.001) levels of mRNA expression, prominent pro-and active forms of MMP-9 and cells immunopositive for MMP-9 were present exclusively in the post-injured tissues from nude mice on Day 24 after wounding. This data suggest that MMP-9 expression in the remodeling phase of wound healing in nude mice could be a major component of their ability for scar-free healing.     

Skin wound healing in different aged Xenopus laevis

Xenopus froglets can perfectly heal skin wounds without scarring. To explore whether this capacity is maintained as development proceeds, we examined the cellular responses during the repair of skin injury in 8‐ and 15‐month‐old Xenopus laevis. The morphology and sequence of healing phases (i.e., inflammation, new tissue formation, and remodeling) were independent of age, while the timing was delayed in older frogs. At the beginning of postinjury, wound re‐epithelialization occurred in form of a thin epithelium followed by a multilayered epidermis containing cells with apoptotic patterns and keratinocytes stained by anti‐inducible nitric oxide synthase (iNOS) antibody. The inflammatory response, early activated by recruitment of blood cells immunoreactive to anti‐tumor necrosis factor (TNF)‐α, iNOS, transforming growth factor (TGF)‐β1, and matrix metalloproteinase (MMP)‐9, persisted over time. The dermis repaired by a granulation tissue with extensive angiogenesis, inflammatory cells, fibroblasts, and anti‐α‐SMA positive myofibroblasts. As the healing progressed, wounded areas displayed vascular regression, decrease in cellularity, and rearrangement of provisional matrix. The epidermis restored to a prewound morphology while granulation tissue was replaced by a fibrous tissue in a scar‐like pattern. The quantitative PCR analysis demonstrated an up‐regulated expression of Xenopus suppressor of cytokine signaling 3 (XSOCS-3) and Xenopus transforming growth factor-β2 (XTGF-β2) soon after wounding and peak levels were detected when granulation tissue was well developed with a large number of inflammatory cells. The findings indicate that X. laevis skin wound healing occurred by a combination of regeneration (in epidermis) and repair (in dermis) and, in contrast to froglet scarless wound healing, the growth to a more mature adult stage is associated with a decrease in regenerative capacity with scar‐like tissue formation. J. Morphol. 274:956–964, 2013. © 2013 Wiley Periodicals, Inc.     

Knockout of Endothelial Cell-Derived Endothelin-1 Attenuates Skin Fibrosis but Accelerates Cutaneous Wound Healing

Endothelin (ET)-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen content compared to that of wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in the knockout mice. The mRNA levels of transforming growth factor (TGF)-β were decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand, skin wound healing was accelerated in ET-1 knockout mice, which was indicated by earlier granulation tissue reduction and re-epithelialization in these mice. The mRNA levels of TGF-β, tumor necrosis factor (TNF)-α and connective tissue growth factor (CTGF) were reduced in the wound of ET-1 knockout mice. In endothelial ET-1 knockout mouse, the expression of TNF-α, CTGF and TGF-β was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and such contradictory effect may be mediated by above molecules. The endothelial cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing, and investigations of the overall regulatory mechanisms of these pathological conditions by ET-1 may lead to a new therapeutic approach.     

Scarless skin wound healing in FOXN1 deficient (nude) mice is associated with distinctive matrix metalloproteinase expression

Similar to mammalian fetuses FOXN1 deficient (nude) mice are able to restore the structure and integrity of injured skin in a scarless healing process by mechanisms independent of the genetic background. Matrix metalloproteinases (MMPs) are required for regular skin wound healing and the distinctive pattern of their expression has been implicated to promote scarless healing. In this study, we analyzed the temporal and spatial expression patterns of these molecules during the incisional skin wounds in adult nude mice. Macroscopic and histological analyses of skin wounds revealed an accelerated wound healing process, minimal granulation tissue formation and markedly diminished scarring in nude mice. Quantitative RT-PCR (Mmp-2, -3, -8, -9, -10, -12, -13, -14 and Timp-1, -2, -3), Western blots (MMP-13) and gelatin zymography (MMP-9) revealed that MMP-9 and MMP-13 showed a unique, bimodal pattern of up-regulation during the early and late phases of wound healing in nude mice. Immunohistochemically MMP-9 and MMP-13 were generally detected in epidermis during the early phase and in dermis during the late (remodeling) phase. Consistent with these in vivo observations, dermal fibroblasts cultured from nude mice expressed higher levels of types I and III collagen, MMP-9 and MMP-13 mRNA levels and higher MMP enzyme activity than wild type controls. Collectively, these finding suggest that the bimodal pattern of MMP-9 and MMP-13 expression during skin repair process in nude mice could be a major component of their ability for scarless healing.