增生性瘢痕成纤维细胞生物学行为及其影响因素

成纤维细胞( fibroblast,FB)是创面修复的主要细胞,它通过迁徙、增殖、分化、合成、分泌及凋亡等生物学行为的有序进行参与创面修复过程.创面正常愈合是FB、细胞因子及细胞外基质间相互作用达到平衡状态的结果.当细胞因子、细胞外基质及FB等的相互调节平衡失调,其一可致FB的生物学行为发生变化,致使增生性瘢痕形成;另外,可致创面愈合减慢,形成慢性难愈性创面.因此,FB的生物学行为与创面正常愈合及增生性瘢痕的形成密切相关.综合了解影响瘢痕FB生物学行为的因素,寻求一条综合调节瘢痕FB生物学行为及其因素的方法,在促进创面正常愈合及防治瘢痕形成均有重要意义.本文就增生性瘢痕FB生物学行为及其影响因素的研究作一综述.     

转化生长因子β1对瘢痕形成的影响

瘢痕形成是一个复杂的病理过程,细胞因子在这个过程中的作用是近年来的研究热点。目前认为转化生长因子β1（transforming growth factor—β1,TGF—β1）与病理性瘢痕的发生发展关系非常密切,可以趋化炎性细胞及组织修复细胞向创面聚集,诱导强烈的单核细胞炎症反应、新生血管形成和促进成纤维细胞发生趋化性迁移、增生和合成细胞外基质（extracellular,ECM）,因此几乎影响到创面愈合和瘢痕形成过程中的所有阶段。现将其作用作一综述。     

口腔黏膜干细胞促进创面愈合的机制研究进展

创面愈合是需要多种细胞及细胞因子参与的复杂过程。在创面愈合过程中, 任何一个环节出现异常, 都可能导致创面发展成为慢性难愈合创面。研究证实多种干细胞可促进创面愈合, 但部分干细胞因存在提取困难、易凋亡、伦理及法律等问题, 临床应用受限。而口腔黏膜干细胞可规避上述问题, 这类干细胞具有胚胎干细胞特性、免疫调节能力, 而且同质性强, 在口腔创面无瘢痕愈合过程中发挥重要作用, 成为促进创面愈合及减少瘢痕形成的研究热点。该文综述口腔黏膜干细胞促进创面愈合的机制研究、临床应用前景及目前存在的问题。     

表皮与真皮之间的相互作用对创面愈合的影响

创面愈合是一个复杂有序的过程,包括炎性细胞、修复细胞的聚集,受损组织的清除,细胞外基质的产生和重塑,最后完成再上皮化或形成瘢痕。它涉及细胞的运动、黏附、通讯、增殖和分化等,也包含细胞内、外物质的代谢和基因的启动、调控等一系列生化和分子生物学反应。这一过程包括炎症反应、细胞增殖、创面成熟和重建3个阶段。     

脂肪干细胞外泌体在皮肤瘢痕形成中的作用研究进展

脂肪干细胞外泌体是脂肪干细胞分泌的亚细胞结构, 是一种可以运输多种细胞成分并通过旁分泌作用于靶细胞的纳米级膜囊泡, 在细胞间的物质交换及信息交流中起着重要作用。瘢痕愈合是皮肤组织损伤后最常见的愈合方式, 病理性瘢痕不仅会造成运动功能障碍, 还会导致畸形, 影响患者外观, 给患者带来生活及精神上的压力。近年来, 许多研究表明脂肪干细胞外泌体内含有多种生物活性分子, 这些分子通过影响成纤维细胞的增殖与迁移及细胞外基质的成分, 从而对减少瘢痕形成及无瘢痕创面愈合起重要作用。该文主要对近年来关于脂肪干细胞外泌体在瘢痕形成中的作用及其机制的文献进行综述, 并对未来脂肪干细胞外泌体在瘢痕治疗中的应用发展进行展望。     

细胞外基质成分及空间形态结构对成纤维细胞生物学行为的影响

成纤维细胞 (Fb)是烧 (创 )伤创面愈合中的主要修复细胞,它通过迁移、增殖、分化、分泌胶原等细胞外基质(ECM)成分,与多种细胞因子及细胞共同起修复作用。Yannas[1]的研究结果表明,脱细胞真皮再生模板植入真皮缺损创面,创面收缩受到强烈抑制,皮肤经历一种再生型的愈合;推测其机     

血管内皮生长因子的作用及其在烧伤创面修复中的意义

血管内皮生长因子(VEGF)是一种特异性作用于血管内皮细胞的多功能细胞因子,它能引起血管通透性增加、细胞外基质成分改变,诱导新生血管形成。VEGF的生物学效应是通过特异的膜受体flt1、KDR及flt4等介导实现的,内皮细胞是VEGF的靶细胞。烧伤是常见的创伤之一,烧伤创面的修复反映了从血管损伤、通透性增加,到新生血管形成及过度增殖的变化过程,临床表现为体液渗出、创面愈合、瘢痕形成。大量研究证实各个阶段均有VEGF参与,现检索相关文献并综述如下。     

瘢痕组织愈合中成纤维细胞凋亡抗性及其临床意义

瘢痕疙瘩（keloid，Ke）是皮肤损伤后组织异常修复的结果。Ke组织中成纤维细胞（fibroblast，FB）过度增生、大量细胞外基质沉积和向正常皮肤侵袭生长，是其区别于肥厚性瘢痕（hypertrophicscar，HS）的重要特征。大量研究证实，细胞的凋亡状态将影响创面愈合、瘢痕形成和预后模式。本研究就细胞凋亡相关基因、调节信号、生长因子及其受体表达对Ke成纤维细胞（keloid．derivedfibroblast，KF）凋亡抗性的影响和临床意义进行综述。     

胚胎无瘢痕愈合的研究进展

胚胎伤口愈合对临床上的伤口愈合后瘢痕形成机制的研究及瘢痕的防治有着重大意义，本文综述了胚胎伤口愈合的周围环境，细胞外基质成分以及胚胎伤愈合模型的最新研究进展。     

皮肤病理性瘢痕形成的细胞与分子生物学机制

皮肤病理性瘢痕是^体皮肤组织损伤后的一种纤维过度增生性疾病，其发病机制涉及众多因素，是各种细胞及细胞因子相互作用、调控的结果。其组织学特点是大量成纤维细胞（FB）增生，细胞外基质（ECM）过度沉积。肥大细胞（MC）释放细胞因子，刺激ECM合成。Caspase蛋白调控FB细胞的凋亡，参与病理性瘢痕的形成。TGF—β、α—MSH、TNF—α、PDGF、IGF-1、IL-8、bFGF等细胞因子及细胞骨架基因相关蛋白、缝隙连接细胞间通讯在病理性瘢痕的形成过程中均发挥重要作用。     

Regulation of wound healing from a connective tissue perspective

Tissue injury resulting in irreversible tissue loss initiates the repair process. The restoration of dermal loss is by scarring, where a new cell population resides in a new connective tissue matrix. The chemical composition of a scar is similar to normal dermis, but the organization of that tissue is altered. The inability of the organism to reassemble collagen into a normal dermal pattern is an attribute of a scar, but in most cases it restores normal function. With impaired scarring, wound dehiscence or chronic wounds arise, whereas the overproduction of scar tissue results in keloid or hypertrophic scarring. In both situations a catastrophic end point occurs. The volume of scar tissue deposited, as well as its organization, is critical for determining the scar's integrity, stability, and restoration of function. The maturation of scar depends on the character of its resident cell populations, the quality of deposited connective tissue, and the interactions between those components. In this Perspective article, the focus will be on the repair process in terms of collagen fiber organization. As our knowledge of cell-cell and cell-matrix interactions in the repair process increases, we may be able to direct the pattern of scar collagen fibers to resemble that of dermis and thereby provide better wound care to the patient of the future.     

Observations on the development and clinical use of artificial skin--an attempt to employ regeneration rather than scar formation in wound healing

Artificial skin, a bilaminar membrane, is grafted on an excised wound immediately following injury. This bilayer membrane, made of a dermal and epidermal portion, is populated in place on the wound bed by the patient's own fibroblasts and epidermal cells producing a permanent skin replacement with an anatomically functioning dermis and epidermis. The dermal portion is a porous collagen-chondroitin 6-sulfate fibrous matrix arranged in a three dimensional pattern closely resembling the fiber pattern of normal dermis. A thin silastic covering serves as a temporary epidermis immediately after grafting until the patient's epidermal cells, seeded on the "neodermis", grow into a confluent epidermal replacement. The autogenous "neodermis" is produced as fibroblasts and vessels migrate from the wound bed into the artificial dermal template and, using the artificial fibers as a scaffolding, synthesize new connective tissue in the collagen fiber pattern of normal dermis rather than the pattern of scar while slowly biodegrading the artificial fibers. This replacement dermis functions as normal dermis and not as scar tissue. The patient's epidermal cells seeded on the "neodermis" grow into a confluent normal appearing epidermis and with the neodermis produce a permanent skin composed of normal functioning dermal and epidermal components produced in situ by the patient's own cells. Artificial skin has been successfully used to permanently replace skin destroyed by burn injuries ranging from 10 to over 95% BSA. The long-term functional results in these patients have been excellent and the long term cosmetic results in preliminary studies tend to be superior to autograft. Artificial skin appears to provide a successful physiologic and cosmetic skin replacement in severe burn injury.     

Observations on the development and clinical use of artificial skin —An attempt to employ regeneration rather than scar formation in wound healing—

Artificial skin, a bilaminar membrane, is grafted on an excised wound immediately following injury. This bilayer membrane, made of a dermal and epidermal portion, is populated in place on the wound bed by the patient's own fibroblasts and epidermal cells producing a permanent skin replacement with an anatomically functioning dermis and epidermis. The dermal portion is a porous collagen-chondroitin 6-sulfate fibrous matrix arranged in a three dimensional pattern closely resembling the fiber pattern of normal dermis. A thin silastic covering serves as a temporary epidermis immediately after grafting until the patient's epidermal cells, seeded on the “neodermis”, grow into a confluent epidermal replacement. The autogenous “neodermis” is produced as fibroblasts and vessels migrate from the wound bed into the artificial dermal template and, using the artificial fibers as a scaffolding, synthesize new connective tissue in the collagen fiber pattern of normal dermis rather than the pattern of scar while slowly biodegrading the artificial fibers. This replacement dermis functions as normal dermis and not as scar tissue. The patient's epidermal cells seeded on the “neodermis” grow into a confluent normal appearing epidermis and with the neodermis produce a permanent skin composed of normal functioning dermal and epidermal components producedin situ by the patient's own cells. Artificial skin has been successfully used to permanently replace skin destroyed by burn injures ranging form 10 to over 95% BSA. The long term functional results in these patients have been excellent and the long term cosmetic results in preliminary studies tend to be superior to autograft. Artificial skin appears to provide a successful physiologic and cosmetic skin replacement in severe burn injury. This report is the gist of a paper read by Dr. Naoki Aikawa, a spokesman for Dr. Burke at the 87th Annual Congress of the Japan Surgical Society, Tokyo, Japan, 1987     

瘢痕形成机制及治疗对策

So far,studies on the mechanism of scar formation have mainly focused on cells,cytokines and extracellular matrix.Some studies have shown that fibroblast is one of the most important element in the pro...     

Comparison of fibrogenesis caused by dermal and adipose tissue injury in an experimental model

Mammalian skin is composed of three layers, the epidermis, the dermis, and the subcutis, which is composed primarily of adipose tissue. The dermal and adipose tissues are involved simultaneously when partial and full‐thickness burns occur, and often induce scar formation. However, little is known about the role of the dermis and adipose tissue injury in scar formation or the difference in fibrogenesis between the two tissues. In this study with female red Duroc pigs, we created flaps of skin with a dermal plane of injury or deeper flaps with an adipose plane of injury on the back. We compared the extent of fibrogenesis by observing the deposition of extracellular matrix as well as the characteristics of cells in the injured area. In skin flaps with a dermal level of tissue injury, scar formation that was characterized by more extracellular matrix deposition and less apoptotic myofibroblasts in the injured area was observed. Our results suggest that scar formation does not correlate with injury at the level of the adipose tissue, and that adipose tissue might serve to alleviate fibrogenesis.     

The application of new biosynthetic artificial skin for long-term temporary wound coverage

Temporary dressings protect wounds from desiccation and infection. In our previous study, we used meshed acellular porcine dermis (APD) to enhance wound healing and decrease wound contraction; however, the wounds showed meshed scar [Wang HJ, Chen TM, Cheng TY. Use of a porcine dermis template to enhance widely expanded mesh autologous split-thickness skin graft growth: preliminary report. J Trauma 1997;42(2):177–82]. In this study, we produced an artificial skin composed of a cross-linked silicon sheet on the surface of APD which we have called silicone acellular porcine dermis (SAPD). This new artificial skin can protect the wound long enough to promote wound healing either by second intention or covered long enough until cultured epithelium autograft (CEA) or autologous skin graft can be harvested for permanent coverage.

We delivered 4 cm × 5 cm full-thickness wound on the back of 350 g Sprague–Dawley rats. Thirty-six rats were divided into two groups. Eighteen rats had SAPD and the other 18 were covered with Biobrane. The wounds were first examined 2 weeks after grafting and followed weekly for an additional 4 weeks to evaluate the wound and study pathological changes by using H.E. and Masson's stains. Wound size was calculated by ruler and analyzed by Student's t-test.

At the 2-week inspection, both SAPD and Biobrane showed tight adherence to the wound with no change of wound size. Both the SAPD and Biobrane dermal templates were pink. In the Biobrane-covered group, the wounds contracted soon after the tie-over dressing was removed. Its dermal layer is a layer of thin porcine dermal substance, which was promptly digested by tissue hyaluronidase and provides no real dermal template. In the SAPD-covered group however, the wound size was maintained significantly from third to sixth week after grafting (p < 0.001). SAPD was designed with thick epidermal silicone and a well-organized porcine dermis so that it incorporates into the recipient wound. Clinically the silicone layer of SAPD dislodged from APD about 6–7 weeks after grafting and was followed by dermal matrix exposure and infection. In pathological examination, much like a human skin graft, new vessels were found in APD about 1 week after grafting with minimal inflammatory cells infiltrated in the graft and wound. Six weeks after grafting, the collagen of APD incorporated into the wound, showing palisade arrangement and no sign of rejection. In the Biobrane group however, the wounds showed severe inflammation, the porcine dermal matrix was digested and disappeared 3 weeks after coverage.

In conclusion, SAPD is a thick biosynthetic artificial skin, which protects the rat wound significantly longer than Biobrane and prevents contraction. We expect that using of SAPD for temporary wound coverage will provide enough time to grow autologous-cultured epithelium or to reharvest skin grafts.     

Dermal preservation using the Versajet hydrosurgery system for debridement of paediatric burns

Loss of dermis is one of the principal factors that contributes to poor scar outcome after severe burn. Dermal loss may be due to the primary injury, surgical management or as a result of infection. Strategies for dermal preservation are therefore important to improve scar quality. We report our early experience using the Versajet hydrosurgery system, to preserve dermal tissues, both directly during surgical debridement and indirectly by reducing infection and optimising the use of biological dressings. In deep partial thickness burns softer necrotic dermis can be removed with the Versajet sparing the underlying tougher viable dermis. In superficial burns the Versajet cleans and removes loose epidermal elements providing an optimal wound surface for the application of biological dressings, even a number of days after injury. Versajet is most useful when the tissue to be removed is softer than that to be left behind.     

Three-dimensional insights into dermal tissue as a cue for cellular behavior

Scar formation after injury is a big problem, which influences the skin function and esthetic appearances. Recent researchers have hinted many directions, one of which has shown that scar formation is related to the loss of integrity in dermal tissues. The structure of dermal tissue, which contains mostly collagen, is not only crucial for the mechanical stability of skin, but also acts as a dermal template, providing contact guidance for regulating cell behavior and restoring normal structure and function to skin that has been damaged by injury. These findings suggest a series of questions. How does contact guidance regulate cell behavior? What is the three-dimensional (3D) architecture of the dermal tissue? How does the native 3D architecture influence cell behavior in vivo? In this paper, combing our recent research, we will review the recent advances in this field, that is, the phenomenon of contact guidance and explore the possible mechanism behind it.     

皮肤组织工程

目的 综述近阶段皮肤组织工程研究领域中的进展。方法 广泛查阅国内外近期在皮肤组织工程研究的文献,着重阐述表皮替代物,真皮替代物,培养的表皮真皮复合皮片的研究进展和重要问题。结果 多数学者认为理想的皮肤替代物应及时重建已人的表皮和真皮结构。目前的研究主要集中在如何尽早移植表皮细胞,并保护移植后细胞的活性和功能,以及研制能更有效地促进细胞功能,诱导创床血植入,移植后可降解,无毒性,无病原携带风险的细胞     

Human acellular dermal wound matrix: evidence and experience

A chronic wound fails to complete an orderly and timely reparative process and places patients at increased risk for wound complications that negatively impact quality of life and require greater health care expenditure. The role of extracellular matrix (ECM) is critical in normal and chronic wound repair. Not only is ECM the largest component of the dermal skin layer, but also ECM proteins provide structure and cell signalling that are necessary for successful tissue repair. Chronic wounds are characterised by their inflammatory and proteolytic environment, which degrades the ECM. Human acellular dermal matrices, which provide an ECM scaffold, therefore, are being used to treat chronic wounds. The ideal human acellular dermal wound matrix (HADWM) would support regenerative healing, providing a structure that could be repopulated by the body's cells. Experienced wound care investigators and clinicians discussed the function of ECM, the evidence related to a specific HADWM (Graftjacket^® regenerative tissue matrix, Wright Medical Technology, Inc., licensed by KCI USA, Inc., San Antonio, TX), and their clinical experience with this scaffold. This article distills these discussions into an evidence‐based and practical overview for treating chronic lower extremity wounds with this HADWM.