Wound healing in denervated tissue

Sacral and trochanteric pressure sores in patients with plegias, and foot ulceration in patients with diabetic neuropathy, are similar because these wounds occur in tissues that do not have normal innervation. While it is recognized that insensitive tissue increases the likelihood of ulceration and recurrence of ulceration, this review attempts to answer the question, Is wound healing impaired in denervated tissue? A review of the scientific literature of the past 35 years demonstrates that all phases of wound healing are impaired in denervated tissue, and these mechanisms are different from those related to one of the underlying diseases, diabetes. Understanding the value of innervation, a goal of wound healing should be to seek strategies that provide reinnervation to these at-risk tissues.     

Wound healing, scar formation and the timing of the correction

An account is given of the histopathological mechanisms of wound healing, before additional factors of influence on cicatrisation are described. Also described is the spectrum of scar patterns, from hairline to keloid. Considerations on proper timing of scar revision and on the age of the patient best suitable for surgical correction have led to the conclusion: the later the intervention, the better the results.     

Wound healing in fetal limb organ culture

The in vitro wound healing responses in whole-limb organ culture of fetal rats at day 19 of gestation were compared with the intrauterine wound repair. In vitro, after a skin incision was made in the lower forelimb, the subcutaneous tissue and the dermis regenerated. Reepithelialization appeared within two to five days. Thus, the wound healing was comparable to the intrauterine fetal wound repair. The whole limb organ culture may be a useful and suitable in vitro test system to study the mechanisms involved in fetal wound healing to search for compounds required in fetal skin regeneration and to test factors tht might influence it.     

Wound healing modulators in a tracheoplasty canine model.

Postsurgical tracheal stenosis results from fibrosis formation due to ischemia. There are healing modulators, hyaluronic acid (HA) and collagen polyvinylpyrrolidone (CPVP), which reduce collagen fibers formation. Thus we can hypothesize that the topical application of one of these modulators can diminish postsurgical tracheal scarring and stenosis. The aim of this work was to evaluate the macroscopic, microscopic, and biochemical changes of tracheal healing after the application of HA or CPVP in a canine tracheoplasty model. The study design was prospective experimental investigation in a canine model. Eighteen mongrel dogs underwent three cervical tracheal rings resection and end-to-end anastomosis. They were randomized into three groups according to treatment: group I (control group) (n = 6), topical application of saline solution on tracheal anastomosis; group II (n = 6), topical application of 15 microg HA on tracheal anastomosis; and group III (n = 6), topical application of 2.5 mg CPVP on tracheal anastomosis. They were evaluated clinical, radiological and tracheoscopically during 4 weeks. They were euthanized at the end of the study time. Macroscopic, microscopic, and biochemical changes of tracheal anastomosis healing were analyzed. Collagen formation was quantified by the Woessner method. All the animals survived the surgical procedure and study period. Macroscopic, radiologic, and endoscopic studies showed that animals in group I developed tracheal stenosis, inflammation, and firm fibrous tissue formation, and histological studies also showed severe inflammatory reaction and fibrosis formation. Groups II (HA) and III (CPVP) showed well-organized thin collagen fibers with minimal inflammatory response. Biochemical evaluation revealed a higher collagen concentration in group I animals (analysis of variance [ANOVA] p < .05 and Tukey p < .01). Thus, hyaluronic acid or collagen polyvinylpyrrolidone administered after tracheal anastomosis diminished the degree of stenosis and inflammatory reaction. Both modulators improved tracheal healing.     

Standardized qualitative evaluation of scar tissue properties in an animal wound healing model

There is a great need to establish reproducible methods for evaluative studies of wound treatment and wound healing. Validation of the healing process through optical techniques, as well as histologic and immunohistochemical methodologies, have been improved and to some extent have become well-established assays. Data relating to biomechanical properties, e.g., evaluation of the tensile strength of scar tissue that forms in experimental wound treatment strategies, are less widely available. We chose the domestic pig as an animal model in which to examine epidermal wound healing. We implanted specially made chambers that served to isolate the wounds and prevent epidermal migration from the edges. We performed histologic and immunohistochemical analyses as well as evaluation of biomechanical qualities of scar tissue using laser tensiometry. Pig skin is well suited for wound healing studies, and wound creation, implantation of the chambers, and the regular changing of dressings could all be carried out in the operating theater. In addition to established macroscopic evaluation and microscopic documentation, the need for objective biomechanical assessment of scar tissue by measuring tensile strength has been met using laser tensiometry. By optimizing methods for measuring tensile strength, it is possible to evaluate the biomechanical quality of scar tissue formed following different courses of wound treatment, as well as histologic assessment.     

胎儿、成人正常皮肤EGFR与FGFR-2表达的研究

目的：观察胎儿与成人正常皮肤中的表皮细胞因子受体（EGFR）与成纤维细胞生长因子受体（FGFR）在细胞膜上表达的差异，探讨胎儿无瘢痕形成的分子机制。方法：对妇产科意外流产的不同妊娠期胎儿和整形外科手术过程中作为供皮区的成人正常皮肤标本，应用免疫组织化学技术观察EGFR与FGFR－2的变化。结果：妊娠台儿的皮肤内EGFR和FGFR－2染色阳性的表皮细胞较多，贯穿于全层上皮，而真皮中成纤维细胞呈阳性标记的极少，随胎龄的增加，两受体的表达增加，成年人正常皮肤中EGFR多集中在表皮细胞的基底层，两种生长因子受体抗体阳性染色的细胞明显多于胎儿皮肤，结论：胎儿和成年人的皮肤中，EGFR染色与FGFR－2表达的差异，可能是造成胎儿无瘢痕愈合的重要因素之一。     

胎兔伤口无瘢痕愈合的形态学和胶原构成研究

目的：探讨胎兔伤口无瘢痕愈合的可能机理及条件。方法：用22－23d的孕兔建立胎兔伤口无瘢痕愈合的动物模型,并与孕兔、成年兔伤口愈合进行比较,对各组兔皮肤切口组织进行光镜和透射电镜检查,胶原含量测定（羟脯氨酸法）及分型。结果：①胎兔切口无急性炎症反应,成纤维细胞（FB）出现早,伤口无瘢痕一期愈合。②胎兔伤口中胶原含量及构成变化不显著;孕兔、成年兔胶原在术后7d时升高（P＜0．05）。结论：无急性炎症反应、皮肤中的FB及胶原构成是胎兔伤口无瘢痕愈合的重要因素。     

Wound healing in foetal sheep: a histological and electron microscope study.

A study was made of the healing of excised, unsutured and sutured skin wounds in foetal sheep of 75, 90 and 120 days gestation and of wounds in newborn lambs and adult ewes. Foetal and postnatal wounds were found to heal in a very similar way. At each stage of development studied, excised wounds contract rapidly and histological and electron microscope examination demonstrates formation of granulation tissue and its maturation to scar tissue in all types of wound. Examination of polyvinyl sponges 7 and 14 days after subcutaneous implantation confirms the ability of foetal sheep to form vascularised scar tissue. The cellular inflammatory response to wounding is much less prominent in foetal than in postnatal sheep, the number and type of extravascular cells reflecting the changes in blood leucocyte content during development. From a very early stage foetal sheep react to insoluble irritants by the formation of multinucleate giant cells.     

Wound healing in vitamin C-deficient and nondeficient guinea pigs: a pilot study

Wound contraction and scar contracture were studied in guinea pigs deficient (stage I) and nondeficient in vitamin C (stage II). Some vitamin C-deficient and some nondeficient animals were subjected to excision of an ellipse of skin measuring 40 X 20 mm in an area not containing panniculus carnosus. The wounds were approximated without undermining. In other animals, the same type of excision was carried out; however, the wounds were left unapproximated. Wound contraction was studied in the unapproximated group and scar contracture was studied in both groups for six months postoperatively. Scar contracture was found to be more significant in animals with unapproximated wounds who were on regular diets, implying a role for vitamin C in this process. Wound contraction was noted to take place in scorbutic and non-scorbutic groups at the same rate. These findings are in line with previous studies done in areas containing panniculus carnosus, implying that the role of this cutaneous muscle in contraction and contracture is not essential in either deficient or nondeficient states. Two animals also developed a remarkably thicker scar than their counterparts while in a deficient state. The relationship between vitamin C deficiency and the formation of hypertrophic scar in guinea pigs is postulated.     

Studies in fetal wound healing: III. Early deposition of fibronectin distinguishes fetal from adult wound healing

Wound healing in the fetus proceeds through a series of steps that differ in the fetus and the adult. At each phase of this complex process, there is signaling between the tissue cells and the wound microenvironment, signals that are mediated by and through the extracellular matrix. We postulate that these signals occur earlier in fetal wounds, resulting in more rapid repair. To investigate this, we compared the first 24 hours of wound healing in the rabbit fetus and adult, using antibodies against key extracellular matrix macromolecular components: laminin, fibronectin, and type-specific collagens I, III, IV, and V. Fibronectin was the first matrix component to be deposited, and was visualized as early as four hours after fetal wounding and 12 hours after adult wounding. There was no evidence of new laminin or collagen deposition in either the fetal or adult wounds at any time point examined. The early deposition of fibronectin, a matrix adhesion molecule that provides a scaffolding for epithelial migration, may underlie the rapid reepithelialization observed in fetal wounds.     

Wound healing in oral mucosa results in reduced scar formation as compared with skin: Evidence from the red Duroc pig model and humans

Scar formation is a common, unwanted result of wound healing in skin, but the mechanisms that regulate it are still largely unknown. Interestingly, wound healing in the oral mucosa proceeds faster than in skin and clinical observations have suggested that mucosal wounds rarely scar. To test this concept, we created identical experimental wounds in the oral mucosa and skin in red Duroc pigs and compared wound healing and scar development over time. We also compared the pig oral mucosal wound healing to similar experimental wounds created in human subjects. The findings showed significantly reduced scar formation at both clinical and histological level in the pig oral mucosa as compared with skin 49 days after wounding. Additionally, the skin scars contained a significantly increased number of type I procollagen immunopositive cells and an increased fibronectin content, while the oral mucosal wounds demonstrated a prolonged accumulation of tenascin-C. Furthermore, the pig oral mucosal wounds showed similar molecular composition and clinical and histological scar scores to human oral mucosal wounds. Thus, the reduced scar formation in the pig oral mucosa provides a model to study the biological processes that regulate scarless wound healing to find novel approaches to prevent scar formation in skin.