Comprehensive characterization of myeloid cells during wound healing in healthy and healing-impaired diabetic mice

Wound healing involves the concerted action of various lymphoid and in particular myeloid cell populations. To characterize and quantitate different types of myeloid cells and to obtain information on their kinetics during wound healing, we performed multiparametric flow cytometry analysis. In healthy mice, neutrophil numbers increased early after injury and returned to near basal levels after completion of healing. Macrophages, monocyte-derived dendritic cells (DCs), and eosinophils were abundant throughout the healing phase, in particular in early wounds, and Langerhans cells increased after wounding and remained elevated after epithelial closure. Major differences in healing-impaired diabetic mice were a much higher percentage of immune cells in late wounds, mainly as a result of neutrophil, macrophage, and monocyte persistence; reduced numbers and percentages of macrophages and monocyte-derived DCs in early wounds; and of Langerhans cells, conventional DCs, and eosinophils throughout the healing process. Finally, unbiased cluster analysis (PhenoGraph) identified a large number of different clusters of myeloid cells in skin wounds. These results provide insight into myeloid cell diversity and dynamics during wound repair and highlight the abnormal inflammatory response associated with impaired healing.     

糖尿病足截肢平面及愈合因素的分析

目的探讨糖尿病足截肢平面和截肢后切口愈合的影响因素。方法收集1998年1月至2009年12月出院的82例糖尿病足截肢患者临床资料,分别分析糖尿病足截肢平面与病程、外周神经障碍、血管狭窄程度、Wagner分级、创面感染情况的相关性,以及截肢后切口愈合情况与年龄、围手术期血糖控制水平、血管狭窄程度、外周神经障碍、Wagner分级、创面感染情况的相关性。结果糖尿病足截肢平面的选择与病程、外周神经障碍、血管狭窄程度有关(P0.05);截肢后切口愈合情况与年龄、血糖控制水平及血管狭窄程度相关(P0.05)。结论糖尿病足截肢平面的选择应通过病程、外周神经病变和血管狭窄程度量化分析;高龄、围手术期血糖控制不佳及重度血管狭窄是糖尿病足截肢后切口愈合欠佳的主要因素。     

Oestrogens and wound healing

During the past few decades several studies have documented the deleterious impact of the menopause on bone mass and cardiovascular disease, and the reduction of risk in this area by HRT. However, the possible effects of the postmenopausal deficiency in ovarian hormones on skin and its repair post-injury, are less well documented. This review provides a survey of the literature that is available regarding the involvement and influence of oestrogens on the various phases of cutaneous repair — inflammation, proliferation and remodelling. Research carried out on the effects of oestrogens, both in terms of deficiency and replacement, on the process of wound healing in various animal models is described and discussed, together with the very limited work undertaken in humans. This area of research is of paramount clinical importance both in terms of financial cost and human suffering, since many chronic wounds such as venous ulcers, pressure sores and burns afflict the elderly population, of whom postmenopausal women comprise the majority. Clinically our aim should be to restore the integrity and function of wounded tissue as rapidly as possible after injury and it is generally believed that a better understanding of the effects of oestrogens on wound healing could lead to improved care of cutaneous wounds, and the treatment of not only the wound but of the postmenopausal woman as a whole.     

IL-33 improves wound healing through enhanced M2 macrophage polarization in diabetic mice

IL-33 is a newly discovered member of the IL-1 family and has been identified as a potent inducer of Th2 type immunity. Emerging evidence imply that IL-33 may also act as an alarm to alert the immune system when released by epithelial barrier tissues during trauma or infection. In this study, we further investigate the potential efficacy of IL-33 on dermal wound healing in streptozotocin–induced diabetic mice. A full-thickness skin wound was generated on the back of diabetic mice and treated with IL-33 or vehicle topically. Our data showed that IL-33 delivery contributed to diabetic wound closure with wounds gaping narrower and exhibiting elevated re-epithelialization. IL-33 promoted the new extracellular matrix (ECM) deposition and angiogenesis formation, which indicates an important role of IL-33 on matrix synthesis and neovascularization. Meanwhile, IL-33 accelerated the development of M2 macrophages in wound sites in vivo, and amplified IL-13-induced polarization of bone marrow-derived macrophages toward a M2 phenotype in vitro. Furthermore, IL-33-amplified M2 macrophages augmented the proliferation of fibroblasts and ECM deposition. All together, these results strongly suggest manipulation of IL-33-mediated signal might be a potential therapeutic approach for diabetic skin wounds.     

硫化氢对糖尿病大鼠皮肤溃疡创面愈合的影响

目的:探讨硫化氢对糖尿病大鼠皮肤溃疡创面愈合的影响。方法:将30只健康雄性SD大鼠,随机分为正常对照组(NDC组)、糖尿病对照组(UDC组)和硫化氢处理组(TDA组),每组10只。腹腔注射链脲佐菌素(65 mg/kg)柠檬酸缓冲液(p H 4.5)建立糖尿病大鼠模型。1周后,将正常大鼠及糖尿病大鼠背部剪开直径为20mm的圆形切口,正常组和糖尿病组大鼠的溃疡创面以空白基质处理,硫氢化处理组则用2%的硫氢化钠涂抹溃疡创面。分别在给药后第5、10、15、20天测定伤口愈合率。21 d后处死大鼠,分别收集血浆以及肉芽组织,检测血浆的凝血酶原时间(prothrombin time,PT)、凝血酶时间(thrombin time,TT)及纤维蛋白原(fibrinogen,FIB),白细胞和淋巴细胞计数,ELISA检测血清超氧化物歧化酶(SOD)活性和丙二醛(MDA)的含量,Western blot检测肉芽组织中血红素加氧酶1(HO-1)和肿瘤坏死因子α(TNF-α)的表达水平;肉芽组织进行HE染色,光镜观察组织形态的变化。结果:与糖尿病组比较,硫氢化钠处理明显加快大鼠伤口愈合(P0.01),提高了血清SOD活性(P0.01),同时降低了MDA水平(P0.01);血液学检测显示,硫氢化钠明显降低白细胞及淋巴细胞数量,延长PT及TT,降低FIB水平。病理切片观察显示,糖尿病对照组大鼠肉芽组织有炎症细胞浸润,胶原纤维排列疏松且不规则,而硫化氢组大鼠肉芽组织中胶原排列整齐,血管生成增多(P0.05)。此外,TDA组HO-1表达明显高于UDC组,而TNF-α的水平则显著低于UDC组。结论:硫化氢可促进糖尿病大鼠伤口愈合,其机制可能与其提高抗炎及抗氧化作用、改善微循环进而修复组织损伤有关。     

P物质对成纤维细胞Rac-1/JNK通路及糖尿病创面愈合的影响

目的 研究外源性P物质(SP)对成纤维细胞迁移的影响及糖尿病小鼠创面愈合的作用.方法 利用Transwell细胞迁移试验、划痕试验检测SP对小鼠成纤维细胞迁移能力的影响.筛选建模成功的糖尿病小鼠20只,随机分为对照组和SP组.分别于皮肤损伤后4、8、12、16、20d,观察创面愈合情况并计算创面愈合率,并于7、14、2...     

Skin wound healing in diabetic β6 integrin‐deficient mice

Jacobsen JN, Steffensen B, Häkkinen L, Krogfelt KA, Larjava HS. Skin wound healing in diabetic β6 integrin‐deficient mice. APMIS 2010; 118: 753–64. Integrin αvβ6 is a heterodimeric cell surface receptor, which is absent from the normal epithelium, but is expressed in wound‐edge keratinocytes during re‐epithelialization. However, the function of the αvβ6 integrin in wound repair remains unclear. Impaired wound healing in patients with diabetes constitutes a major clinical problem worldwide and has been associated with the accumulation of advanced glycated endproducts (AGEs) in the tissues. AGEs may account for aberrant interactions between integrin receptors and their extracellular matrix ligands such as fibronectin (FN). In this study, we compared healing of experimental excisional skin wounds in wild‐type (WT) and β6‐knockout (β6^?/?) mice with streptozotocin‐induced diabetes. Results showed that diabetic β6^?/? mice had a significant delay in early wound closure rate compared with diabetic WT mice, suggesting that αvβ6 integrin may serve as a protective role in re‐epithelialization of diabetic wounds. To mimic the glycosylated wound matrix, we generated a methylglyoxal (MG)‐glycated variant of FN. Keratinocytes utilized αvβ6 and β1 integrins for spreading on both non‐glycated and FN‐MG, but their spreading was reduced on FN‐MG. These findings indicated that glycation of FN and possibly other integrin ligands could hamper keratinocyte interactions with the provisional matrix proteins during re‐epithelialization of diabetic wounds.     

壳寡糖在糖尿病皮肤伤口愈合中的应用及研究进展

糖尿病慢性皮肤伤口的愈合,是临床治疗中的难点和基础研究中的热点。传统治疗方法效果并不理想,而组织工程技术的发展,为其治疗提供了新途径。现今已有将壳寡糖作为伤口敷料的研究,并引起越来越多的关注,但关于壳寡糖用于糖尿病难愈性创面的研究并不多。本篇综述将概述壳寡糖促进伤口愈合的生物学机制及特点,以及糖尿病皮肤创面的病理学改变,总结壳寡糖在糖尿病皮肤伤口愈合中的研究进展。     

富血小板血浆在糖尿病足创面修复中的作用研究

目的探究富血小板血浆(PRP)在糖尿病足创面修复中的作用。 方法选取2019年2月至2020年1月新疆维吾尔自治区人民医院收治的糖尿病足患者120例,根据治疗方式的不同将其分为对照组和研究组,每组各60例。所有患者经抗感染、控制血糖及手术清创处理,并对创面进行照相。对照组采用常规换药治疗,研究组将PRP均匀完整覆于创面,2组均使用凡士林纱布对创面进行覆盖,按需换药/清创,直至创面完全愈合。对2组患者的创面愈合率、创面完全愈合时间及炎症反应阳性率、换药/清创次数进行统计分析;数据比较采用t检验和χ²检验。 结果换药后第6天、第9天、第18天,研究组的创面愈合率分别为(18.90±7.18)%、(58.49±9.80)%、(96.70±5.39)%,分别优于对照组[(14.76±6.79)%、(43.76±7.29)%、(80.51±7.40)%],差异均有统计学意义(t＝2.814、8.092、11.860, P<0.05);研究组创面完全愈合时间为(21.49±3.18) d,短于对照组[(27.46±3.79) d],差异有统计学意义(t＝8.094, P<0.05);研究组炎症反应阳性率为8.68%,明显低于对照组(35.12%),差异有统计学意义(χ²＝6.534, P<0.05);研究组的换药与清创次数分别为(7.19±1.08)、(2.28±0.59)次,均低于对照组[(9.68±1.47)、(5.37±1.29)次],差异均有统计学意义(t＝4.583、7.282, P<0.05)。 结论应用PRP进行糖尿病足创面的外用对糖尿病足患者创面修复疗效更佳,可缩短愈合时间,减少炎症反应阳性率、换药/清创次数,值得应用。     

α7nAChR的激活通过抑制TNF-α表达促进糖尿病小鼠伤口愈合

 目的：观察糖尿病小鼠伤口愈合期间巨噬细胞浸润及肿瘤坏死因子 α（TNF-α）表达特征,探讨α7烟碱型乙酰胆碱受体（α7nAChR）特异性激动剂PNU-282987是否可通过抑制TNF-α表达促进糖尿病小鼠伤口的愈合。方法：(1) 制作糖尿病小鼠切创模型（糖尿病组）,正常小鼠在相同部位制作相同大小创口作为对照（对照组）,分别于切创后1 d、3 d、5 d、10 d、14 d和21 d（每个时间段5只）提取创口样本。免疫组化观察创口中巨噬细胞和成纤维细胞数量,Western blotting检测TNF-α表达水平,Masson染色观察胶原沉积情况。 (2) 在糖尿病小鼠切创后,选择合适的干预时间窗进行PNU-282987干预,然后观察上述指标变化。结果：(1) 与对照组相比,糖尿病组创口愈合明显延迟,在切创初期的伤口中巨噬细胞数量和TNF-α表达水平较低（P<0.05）,而切创5 d后的伤口巨噬细胞数量和TNF-α表达水平显著增加（P<0.05）,成纤维细胞数量和胶原含量减少（P<0.05）。 (2) 在切创5 d后对糖尿病小鼠腹腔注射PNU-282987,可显著减少伤口中TNF-α表达,提高成纤维细胞数量和胶原含量,促进伤口愈合。结论：糖尿病伤口愈合具有炎症反应发生迟但不易消退的特征。在炎症反应明显期激活α7nAChR可抑制TNF-α表达,促进糖尿病小鼠的伤口愈合。     

扰乱昼夜节律对小鼠角膜创伤修复的影响

目的:本研究旨在观察昼夜节律对角膜创伤修复的影响。方法:选用C57BL/6雄性小鼠,在小鼠角膜中央直径为2 mm的圆形区域,用高尔夫样刀机械性去除其上皮层,使用荧光素钠显色创伤面积,动态观察上皮层修复的动力学,并观察白细胞、血小板和分裂细胞的动态变化。结果:全昼(12 h light/12 h light,LL)和全夜(12 h dark/12 h dark,DD)组角膜创伤修复速率小于对照组(12 h light/12 h dark,LD),表现为再上皮化延迟、上皮细胞数量降低、血管扩张直径增大、白细胞和血小板募集的发生延迟,但白细胞和血小板数目显著增多。结论:扰乱昼夜节律延迟炎症反应的发生,但加剧炎症反应;延迟再上皮化过程,最终显著抑制角膜创伤修复过程。     

皮肤成纤维细胞在创面愈合中的研究进展

皮肤成纤维细胞是参与创面愈合的主要修复细胞,近年来其异质性及其与周围细胞间的通讯正逐渐引起重视.真皮成纤维细胞亚群主要包括乳头状成纤维细胞和网状成纤维细胞,对创面愈合发挥不同的作用.成纤维细胞通过自分泌和旁分泌信号分子与周围细胞之间相互作用构成创面微环境,影响创面愈合.慢性创面中的成纤维细胞表现出多种功能障碍.本文就成...     

Allotransplantation of ascorbic acid-treated fibroblasts improves healing of excisional cutaneous wound in diabetic rats

The purpose of this study was to evaluate the effects of ascorbic acid (AA)-treated fibroblasts transplantation on excisional diabetic wound healing. An excisional wound was created between the shoulders of streptozotocin-induced diabetic rats. On day three, 1 ml of PBS, ?1 × 10⁶ ?intact homologous fibroblasts, and ?1 × 10⁶ ? fibroblasts treated with 50 μM AA were injected subcutaneously around the wound edges in control, treatment-1 and treatment-2 groups, respectively. In the sham group, the wound was left intact. Wound area was measured by planimetry. On day 15, samples were harvested for histopathological examination and hydroxyproline content. Wound area in treatment-1 and ? 2 groups was ?significantly decreased compared to other groups, on days 11 and 15. The hydroxyproline content was significantly lower in the control group compared to the other groups. Histopathology revealed significant increases in the number of neovessels, macrophages, lymphocytes and fibroblasts in the treatment-2 group compared to the other groups. Trichrome staining showed the highest level of collagen deposition and orientation in the treatment-2 group. In conclusion, allotransplantation of ?50 μM ? AA-treated fibroblasts ?could result in progressive healing and improved reparative indices of excisional dermal wound in diabetic rats.     

Antibacterial and cell-adhesive polypeptide and poly(ethylene glycol) hydrogel as a potential scaffold for wound healing

The ideal wound-healing scaffold should provide the appropriate physical and mechanical properties to prevent secondary infection, as well as an excellent physiological environment to facilitate cell adhesion, proliferation and/or differentiation. Therefore, we developed a synthetic cell-adhesive polypeptide hydrogel with inherent antibacterial activity. A series of polypeptides, poly(Lys)_x(Ala)_y (x + y = 100), with varied hydrophobicity via metal-free ring-opening polymerization of NCA-Lys(Boc) and NCA-Ala monomers (NCA = N-carboxylic anhydride) mediated by hexamethyldisilazane (HMDS) were synthesized. These polypeptides were cross-linked with 6-arm polyethylene glycol (PEG)-amide succinimidyl glutarate (ASG) (M_w = 10 K) to form hydrogels with a gelation time of five minutes and a storage modulus (G′) of 1400-3000 Pa as characterized by rheometry. The hydrogel formed by cross-linking of poly(Lys)₆₀(Ala)₄₀ (5 wt.%) and 6-arm PEG-ASG (16 wt.%) (Gel-III) exhibited cell adhesion and cell proliferation activities superior to other polypeptide hydrogels. In addition, Gel-III displays significant antibacterial activity against Escherichia coli JM109 and Staphylococcus aureus ATCC25923. Thus, we have developed a novel, cell-adhesive hydrogel with inherent antibacterial activity as a potential scaffold for cutaneous wound healing.     

Sonic hedgehog促1型糖尿病小鼠的伤口愈合

目的：研究sonic hedgehog（Shh）及其受体Ptc1在糖尿病小鼠伤口愈合中的作用。方法：分别在正常和链脲佐菌素（STZ）诱导的糖尿病小鼠建立皮肤损伤模型,Western印迹检测Shh和Ptc1的蛋白水平;观察外源性Shh或Ptc1抑制剂cyclopamine对伤口愈合的影响。结果：（1）正常小鼠损伤后皮肤组织中的Shh和Ptcl蛋白质表达明显升高;外源性Shh对伤口愈合无明显促进作用,但cyclopamine可以明显地抑制伤口愈合;（2）STZ诱导的糖尿病小鼠,其皮肤组织中内源性的Shh和Ptcl蛋白水平明显下调;（3）外源性Shh可显著促进糖尿病小鼠伤口的愈合,且呈浓度依赖性;Cyclopamine则明显地抑制糖尿病小鼠的伤口愈合。结论：Shh-Ptc1通路参与了皮肤伤口愈合,糖尿病伤口愈合延迟与Shh-Ptc1表达下调有关。     

MMP-9/TIMP-1表达在糖尿病鼠皮肤伤口愈合过程中的变化及意义初探

目的：观察基质金属蛋白酶-9（MMP-9）、组织金属蛋白酶抑制剂-1（TIMP-1）的表达和MMP-9/TIMP-1比值在糖尿病组和正常组大鼠皮肤伤口愈合过程中不同时点表达的动态变化，探讨其可能的作用机制。 方法:糖尿病大鼠形成6周后行皮肤伤口造模，采用HE染色、Masson染色和免疫组织化学方法评估伤口形成后3、7、14 d伤口组织的再上皮化、炎症细胞浸润、肉芽组织厚度、新生血管形成和胶原纤维密度的情况；通过逆转录-聚合酶链反应(RT-PCR)和Western印迹检测术后不同时点MMP-9、TIMP-1在伤口组织中的表达情况。结果:糖尿病大鼠伤口愈合明显迟缓。术后第3 d两组间胶原纤维、肉芽组织、新生血管和再上皮化没有差异，术后第7 d糖尿病组以上指标得分均低于正常组，第14 d这种趋势更加明显；而第3 d至14 d，糖尿病组的单核巨噬细胞浸润得分均低于正常组。术后第3 d两组MMP-9表达均达高峰，第7、14 d呈逐渐下降趋势，糖尿病组MMP-9表达水平在各时点均高于正常组；术后第3 d两组TIMP-1表达均达高峰，第7、14 d呈逐渐下降趋势，糖尿病组TIMP-1表达水平在各时点均低于正常组；正常组MMP-9/TIMP-1蛋白水平比值始终维持在一个动态平衡的稳定水平，而糖尿病组却长期处于高水平状态。结论:异常的胶原产生、新生血管重建、炎症反应、再上皮化、肉芽形成可能是糖尿病鼠创面愈合减慢的组织病理学基础；皮肤组织MMP-9/TIMP-1的平衡性改变可能是这种组织病理学异常的重要原因之一。     

LED红光对糖尿病大鼠创面愈合的影响

目的探讨LED红光照射对糖尿病大鼠创面愈合的作用及相关机制。 方法将30只4周龄雄性SD大鼠按随机数字表法分为正常创面组、糖尿病创面组、红光治疗糖尿病创面组,每组10只。红光治疗糖尿病创面组及糖尿病创面组大鼠高脂饮食4周,正常创面组大鼠正常饮食。饲养4周后对红光治疗糖尿病创面组及糖尿病创面组大鼠按50 mg/kg的量腹腔注射10 mg/mL的链脲佐菌素(STZ)制作糖尿病大鼠模型,2组大鼠均造模成功。造模成功后在3组大鼠的背部两侧各制造2个1.5 cm×1.5 cm的全层皮肤缺损创面,每2 d对大鼠创面进行酒精消毒1次,红光治疗糖尿病创面组大鼠每次消毒后对创面进行LED红光照射5 min,能量密度为20 J/cm²,另外2组大鼠不进行LED红光照射。在观察第7、10、14、21天,观察红光治疗糖尿病创面组大鼠创面有无出现皮疹、红肿、水疱、烫伤等光照不良反应;肉眼观察3组大鼠创面愈合情况;统计3组大鼠创面愈合率。观察第10天从各组随机取2只大鼠,处死后取背部创面组织,固定后,进行苏木精-伊红染色观察创面新生血管情况及肉芽组织生长情况;采用免疫荧光法检测各组大鼠创面组织中CD34、血管内皮细胞生长因子(VEGF)表达情况。数据比较采用单因素方差分析和LSD-t检验。 结果观察第7、10、14、21天,红光治疗糖尿病创面组大鼠经LED红光照射后皮肤未见皮疹、红肿、水疱、烫伤等光照不良反应。在各个观察时间点,肉眼观察正常创面组及红光治疗糖尿病创面组创面愈合情况均优于糖尿病创面组,且正常创面组创面愈合情况略优于红光治疗糖尿病创面组;观察第7、10、14、21天,正常创面组的创面愈合率分别为(34.62±2.116)%、(53.83±7.92)%、(70.20±5.41)%、(95.65±2.58)%,红光治疗糖尿病创面组创面愈合率分别为(31.76±2.44)%、(50.48±4.54)%、(66.26±11.35)%、(93.96±2.80)%,糖尿病创面组创面愈合率分别为(23.67±4.18)%、(42.71±3.40)%、(53.77±7.74)%、(84.07±4.43)%,3组比较差异均有统计学意义(F＝34.69、10.35、10.32、34.40,P<0.05);观察第7、10、14、21天,正常创面组及红光治疗糖尿病创面组创面愈合率始终高于糖尿病创面组,差异均有统计学意义(P<0.05);观察第7、10天,正常创面组创面愈合率高于红光治疗糖尿病创面组,差异均有统计学意义(t＝2.80、3.26,P<0.05),观察第14、21天,正常创面组创面愈合率仍高于红光治疗糖尿病创面组,但差异均无统计学意义(t＝1.16、1.40,P>0.05)。观察第10天,创面组织苏木精-伊红染色显示,正常创面组内含大量新生毛细血管,肉芽组织内胶原及细胞排列紧密有序;红光治疗糖尿病创面组见较多新生毛细血管,肉芽组织内胶原及细胞较多,但少于正常创面组;而糖尿病创面组新生血管最少,肉芽组织内细胞及胶原稀疏。免疫荧光法检测创面组织中CD34、VEGF表达情况可见,正常创面组CD34、VEGF表达高于红光治疗糖尿病创面组,而红光治疗糖尿病创面组表达高于糖尿病创面组。 结论LED红光可促进糖尿病大鼠创面组织中CD34、VEGF表达,促进血管新生,进而促进创面愈合。     

The in vitro characterization of a gelatin scaffold,prepared by cryogelation and assessed in vivo as a dermal replacement in wound repair

A sheet gelatin scaffold with attached silicone pseudoepidermal layer for wound repair purposes was produced by a cryogelation technique. The resulting scaffold possessed an interconnected macroporous structure with a pore size distribution of 131 ± 17 μm at one surface decreasing to 30 ± 8 μm at the attached silicone surface. The dynamic storage modulus (G′) and mechanical stability were comparable to the clinical gold standard dermal regeneration template, Integra®. The scaffolds were seeded in vitro with human primary dermal fibroblasts. The gelatin based material was not only non-cytotoxic, but over a 28 day culture period also demonstrated advantages in cell migration, proliferation and distribution within the matrix when compared with Integra®. When seeded with human keratinocytes, the neoepidermal layer that formed over the cryogel scaffold appeared to be more advanced and mature when compared with that formed over Integra®. The in vivo application of the gelatin scaffold in a porcine wound healing model showed that the material supports wound healing by allowing host cellular infiltration, biointegration and remodelling. The results of our in vitro and in vivo studies suggest that the gelatin based scaffold produced by a cryogelation technique is a promising material for dermal substitution, wound healing and other potential biomedical applications.     

Topical folinic acid enhances wound healing in rat model

Purpose

Folic acid is an essential vitamin participating in DNA synthesis and repair. Recently folic acid has been shown to stimulate DNA-repair capacity in dermal fibroblasts in response to injury. Thus, the present study aimed to investigate the effects of topical folinic acid, a 5-formyl derivative of tetrahydrofolic acid, on wound healing using rat wound model.

An in vitro examination of an extracellular matrix scaffold for use in wound healing

This paper describes evidence that an extracellular matrix (ECM) secreted by human umbilical vein endothelial cells (HUVECs) assembled on gelatin coated plates overlaid by a mixed matrix secreted by human dermal microvascular endothelial cells (HDMECs) and human dermal fibroblasts provides a viable acellular scaffold for use in wound healing. Trypsinized epidermal keratinocytes or colonies from Dispase-digested fresh and cadaver skin tissue adhered and proliferated on either HUVECs ECM/gelatin or mixed matrix overlaid on HUVECs ECM/gelatin. An epithelial-mesenchymal interaction, previously thought to be tissue-specific, was exposed as well as concomitant integrin versatility. Furthermore, heterologous HDMECs and dermal fibroblasts attached and proliferated on the mixed matrix as well as HUVECs ECM. The conditioned medium from HUVECs (HUVECs CM) was found to neutralize the lingering after effects of Dispase, and could be used for the tissue culture of epidermal keratinocytes, HDMECs and dermal fibroblasts, which share related extracellular secretions. Taken together, these results indicate that cultured epithelial autografts can be redesigned to include both epithelial and dermal elements, and advances the acellular 'sandwich' ECM scaffold as a possible structural replacement for the lamina densa and lamina lucida, damaged or completely missing in some wounds and burns.