Cutaneous Wound Healing

Published on Sep 2, 1999in The New England Journal of Medicine74.699
· DOI :10.1056/NEJM199909023411006
Adam J. Singer67
Estimated H-index: 67
(SBU: Stony Brook University),
Richard A.F. Clark78
Estimated H-index: 78
The primary function of the skin is to serve as a protective barrier against the environment. Loss of the integrity of large portions of the skin as a result of injury or illness may lead to major disability or even death. Every year in the United States more than 1.25 million people have burns1 and 6.5 million have chronic skin ulcers caused by pressure, venous stasis, or diabetes mellitus.2 The primary goals of the treatment of wounds are rapid wound closure and a functional and aesthetically satisfactory scar. Recent advances in cellular and molecular biology have greatly expanded our understanding . . .
📖 Papers frequently viewed together
790 Citations
1,380 Citations
1,177 Citations
#1Neta Ilan (Yale University)H-Index: 59
#2Sepi MahootiH-Index: 10
Last. Joseph A. MadriH-Index: 102
view all 3 authors...
Angiogenesis, the formation of new blood vessels from pre-existing ones, occurs during development, wound healing and cancer and involves stages that orchestrate a network of cooperative interactions. Peptide growth factors and extracellular matrix (ECM) components are two major groups of angiogenesis mediators. Among the different ECM proteins, collagens have been well-associated with in vivo angiogenesis. Using human umbilical vein endothelial cells (HUVEC) grown in 3-D collagen gels we show t...
248 Citations
#1Miriam A.M. Loots (UvA: University of Amsterdam)H-Index: 6
#2Evert N. Lamme (UvA: University of Amsterdam)H-Index: 7
Last. Esther MiddelkoopH-Index: 60
view all 6 authors...
In diabetic patients, wound healing is impaired. We studied the pathogenesis behind this clinical observation by characterizing the pattern of deposition of extracellular matrix (ECM) molecules and the cellular infiltrate in chronic (>8 wk) diabetic wounds, compared with chronic venous ulcers and an acute wound healing model. Punch biopsies were obtained from the chronic ulcer margins and control samples were collected from upper leg skin 5, 19, 28 d and 12 and 18 mo postwounding (p.w.). T cells...
411 CitationsSource
#1Ghassan M. Saed (HFH: Henry Ford Hospital)H-Index: 36
#2Daniel A. LadinH-Index: 6
Last. David P. FivensonH-Index: 30
view all 6 authors...
Background Keloids are the result of a dysregulated wound healing process. They are characterized by the formation of excess scar tissue that proliferates beyond the boundaries of the original wound. Somatic mutations of p53 have been implicated as causal events in up to 50% of all human malignancies. In addition, p53 has been shown to play an important role in controlling cell proliferation and apoptosis. We hypothesize that mutations in p53 can lead to a hyperproliferative state that can resul...
79 CitationsSource
#1Marianne Madlener (MPG: Max Planck Society)H-Index: 7
#2William C. Parks (WashU: Washington University in St. Louis)H-Index: 88
Last. Sabine Werner (MPG: Max Planck Society)H-Index: 99
view all 3 authors...
Abstract During cutaneous wound healing a number of migratory and remodeling events occur that require the action of matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs). In this study, we analyzed the temporal and spatial expression patterns of these molecules during the healing of murine excisional skin wounds. Our data imply that defined phases of repair rely on distinct repertoires of MMP activity and TIMP counterregulation. Reepithelialization was found to be associated wit...
297 CitationsSource
#1Nicholas N. Nissen (Loyola University Medical Center)H-Index: 5
#1Nicholas N. Nissen (LUC: Loyola University Chicago)H-Index: 1
Last. Luisa A. DiPietroH-Index: 45
view all 6 authors...
Angiogenesis is an essential component of normal wound repair, yet the primary mediators of wound angiogenesis have not been well described. The current study characterizes the contribution of vascular endothelial cell growth factor (VEGF) to the angiogenic environment of human surgical wounds. Surgical wound fluid samples (n = 70) were collected daily for up to 7 postoperative days (POD) from 14 patients undergoing mastectomy or neck dissection. VEGF levels in surgical wound fluid were lowest o...
640 Citations
#1M. Machesney (QMUL: Queen Mary University of London)H-Index: 1
#2Nicholas TidmanH-Index: 4
Last. Irene M. LeighH-Index: 104
view all 5 authors...
The etiology of hypertrophic scarring, a pathological end point of wound healing, is unknown. The scars most commonly occur when epithelialization has been delayed during, for example, the healing of deep dermal burn wounds. Hypertrophic scars are conventionally described as a dermal pathology in which the epidermis has only a passive role. In this study, the expression of keratin intermediate filament proteins and filaggrin has been investigated in the epidermis of hypertrophic scars and site-m...
132 Citations
#1Vincent Falanga (UM: University of Miami)H-Index: 78
#2David J. MargolisH-Index: 110
Last. Jan Hardin-YoungH-Index: 2
view all 9 authors...
Objective To test the safety, efficacy, and immunological impact of a cultured allogeneic human skin equivalent (HSE) in the treatment of venous ulcers. Design Prospective, randomized study. Setting Multicenter study in the outpatient setting. Intervention Each patient with a venous ulcer received either compression therapy alone or compression therapy and treatment with HSE. The patients were evaluated for HSE safety, complete (100%) ulcer healing, time to wound closure, wound recurrence, and i...
553 CitationsSource
#1Maarit Vaalamo (HYKS: Helsinki University Central Hospital)H-Index: 11
#2Laura Mattila (UTU: University of Turku)H-Index: 3
Last. Ulpu Saarialho-Kere (HYKS: Helsinki University Central Hospital)H-Index: 71
view all 7 authors...
Proteolysis is an intrinsic component of cutaneous wound repair and several matrix metalloproteinases have been shown to participate in various stages of this process. Therefore, we investigated the expression of a novel metalloproteinase, collagenase-3 (MMP-13), in normally healing cutaneous wounds and chronic venous ulcers. MMP-13 was expressed abundantly by fibroblasts deep in the chronic ulcer bed but was not detected in epidermis and all the acute wounds. The spatial expression of MMP-13 di...
243 CitationsSource
#1Kelli M. Bullard (UCSF: University of California, San Francisco)H-Index: 23
#2Darrell L. Cass (UCSF: University of California, San Francisco)H-Index: 38
Last. N. Scott Adzick (UCSF: University of California, San Francisco)H-Index: 98
view all 4 authors...
Abstract Fetal dermal wounds heal without scarring. Because wound repair requires extracellular matrix turnover, the authors hypothesized that fetal skin would have increased levels of proteinases responsible for matrix degradation compared with adult skin. It was further hypothesized that transforming growth factor beta-1 (TGF-β1) induces scarring in fetal skin by altering proteinase synthesis. A model of human fetal skin transplanted subcutaneously onto immunodeficient mice was used to study t...
45 CitationsSource
#1M L Iruela-Arispe (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 1
#2Harold F. Dvorak (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 131
: Angiogenesis, the formation of new blood vessels from a pre-existing vasculature, is tightly regulated in normal adults. Under physiological circumstances, angiogenesis occurs in only a few instances; e.g., the female reproductive system in response to ovulation or gestation, the normal hair cycle, etc. In these examples, growth of new capillaries is tightly controlled by an interplay of growth regulatory proteins which act either to stimulate or to inhibit blood vessel growth. Normally, the b...
260 CitationsSource
Cited By4115
#1Hua ZhengH-Index: 5
#2Shenqiang WangH-Index: 7
Last. Qiuyu ZhangH-Index: 59
view all 8 authors...
Abstract null null Overcoming multidrug-resistant (MDR) bacterial infection and simultaneously enhancing wound healing/skin reconstruction are still critical challenges for both clinic practice and fundamental research. The single modal therapy strategy is usually inefficient. Herein, for the first time, multifunctional MXene@CeO2 nanocomposites were prepared by combining the 2D antibacterial conductive Ti3C2Tx MXenes and antioxidant CeO2 and applied in developing multifunctional hydrogel scaffo...
#1Mengzhen Zhang (NKU: Nankai University)H-Index: 2
#2Xinyun Zhai (NKU: Nankai University)H-Index: 2
Last. Yaping Du (NKU: Nankai University)H-Index: 42
view all 6 authors...
Abstract Oxidative stress, which is induced by the overproduced free radicals around inflammation, is one of the most important factors to delay the wound healing process. Much efforts have been focused on wound repair with an emphasis on exploring novel biomaterials which have prominent antioxidant activity and good biocompatibility. In this work, cerium-doped carbon nanodots (Ce-CNDs) are fabricated by a simple hydrothermal method. The as-prepared Ce-CNDs have monodispersed and ultrasmall size...
#1Yan Li (SDU: Shandong University)
#1Yan Li (SDU: Shandong University)
Last. Wenguo Cui (SJTU: Shanghai Jiao Tong University)H-Index: 53
view all 0 authors...
Abstract null null Various types of biological materials have been developed and applied for tissue regeneration and wound repair. Among them, hydrogel fibers obtained by combining hydrogel with electrospinning provide good tissue matching properties in terms of structure and biological function, thus attracting extensive attention from researchers. Electrospun fibers are made of polymers with adjustable mechanical and degradation properties. Their three-dimensional network structure with a high...
#1Ling-Chun Chen (YPU: Yuanpei University)H-Index: 1
#1Ling Chun Chen (YPU: Yuanpei University)H-Index: 11
Last. Chien Ming Hsieh (TMU: Taipei Medical University)H-Index: 7
view all 6 authors...
Abstract Composite dressing composed of Rhizochitosan and RegenplexTM to promote wound healing were assessed. Rhizochitosan was fabricated by deacetylation of Rhizochitin, which obtained by simply depigmenting sporangium-free mycelial mattress produced from Rhizopus stolonifer F6. Physicochemical characterizations of Rhizochitosan demonstrated that it contained 13.5% chitosan with a water-absorption ability of 35-fold dry weight and exhibiting hydrogel nature after hydration. In a wound-healing ...
#1Junjie Chi (SEU: Southeast University)H-Index: 8
#2Changmin Shao (CAS: Chinese Academy of Sciences)H-Index: 14
Last. Fangfu Ye (CAS: Chinese Academy of Sciences)
view all 5 authors...
Abstract Biological patches with controllable surface wettability have received extensive attention in fundamental research and clinical practice. Herein, we present a novel Janus porous patch with anisotropic surface wettability derived from microfluidic droplet templates for wound healing. Such patch was fabricated by magnetic-induced assembly and replicating of hydrophilic and hydrophobic colloidosomes into a double-layered, close-packing film. The resultant film displayed anisotropic surface...
#1José Leal (University of Freiburg)
#2Nicole Jedrusik (University of Freiburg)H-Index: 3
Last. Maria Asplund (Luleå University of Technology)H-Index: 15
view all 0 authors...
Abstract null null null null Electrotaxis is a naturally occurring phenomenon in which ionic gradients dictate the directed migration of cells involved in different null biological processes null such as wound healing, null null embryonic development , or cancer metastasis. To investigate these processes, direct current (DC) has been used to generate electric fields capable of eliciting an electrotactic response in cells. However, the need for metallic electrodes to deliver said currents has hin...
#1Gang Zheng (WMU: Wenzhou Medical College)H-Index: 13
#2Di Zhang (WMU: Wenzhou Medical College)H-Index: 6
Last. Li-Yan Shen (WMU: Wenzhou Medical College)H-Index: 2
view all 10 authors...
Abstract The local oxidizing microenvironment and bacterial infection, as crucial internal and external factors that hinder the healing of diabetic wounds, are two main issues to be addressed in the design of novel wound dressing materials. As an attempt to provide optimal solution to the aforementioned problems, free-standing (FS) polyelectrolyte multilayer films (PEMs) loaded with bis[2-(4-hydroxyphenyl) benzimidazole] (BHPB) were constructed by layer-by-layer (LBL) self-assembly method. The e...
#1M. Fujimori (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 2
#2Yasushi Kimura (UMass: University of Massachusetts Amherst)H-Index: 1
Last. Govindarajan Srimathveeravalli (UMass: University of Massachusetts Amherst)H-Index: 3
view all 0 authors...
#1Imran Khan (NIH: National Institutes of Health)H-Index: 21
#2Saeed Ur Rahman (UB: University at Buffalo)H-Index: 7
Last. Praveen R. Arany (UB: University at Buffalo)H-Index: 25
view all 0 authors...
The severity of tissue injury in burn wounds from associated inflammatory and immune sequelae presents a significant clinical management challenge. Among various biophysical wound management approaches, low dose biophotonics treatments, termed Photobiomodulation (PBM) therapy, has gained recent attention. One of the PBM molecular mechanisms of PBM treatments involves photoactivation of latent TGF-β1 that is capable of promoting tissue healing and regeneration. This work examined the efficacy of ...
#1Wenqian Zhang (HUST: Huazhong University of Science and Technology)
#2Lang Chen (HUST: Huazhong University of Science and Technology)H-Index: 9
Last. Mengfei Liu (HUST: Huazhong University of Science and Technology)H-Index: 6
view all 0 authors...
Ulcers are a lower-extremity complication of diabetes with high recurrence rates. Oxidative stress has been identified as a key factor in impaired diabetic wound healing. Hyperglycemia induces an accumulation of intracellular reactive oxygen species (ROS) and advanced glycation end products, activation of intracellular metabolic pathways, such as the polyol pathway, and PKC signaling leading to suppression of antioxidant enzymes and compounds. Excessive and uncontrolled oxidative stress impairs ...