Thomas A Mustoe

Thomas A Mustoe
Northwestern University | NU · Division of Plastic Surgery

About

368
Publications
46,650
Reads
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18,637
Citations
Citations since 2016
21 Research Items
5980 Citations
201620172018201920202021202202004006008001,000
201620172018201920202021202202004006008001,000
201620172018201920202021202202004006008001,000
201620172018201920202021202202004006008001,000

Publications

Publications (368)
Article
Background: Chronic or delayed healing wounds constitute an ever-increasing burden on healthcare providers and patients alike. Thus, therapeutic modalities that are tailored to particular deficiencies in the delayed wound healing response are of critical importance to improve clinical outcomes. Human amnion-derived viable and devitalized allograft...
Article
Damage to epidermis results in loss of barrier function and resultant pathological inflammatory signaling, triggering further damage to the skin. Here we investigate transcriptomic datasets generated from varied skin pathologies associated with disrupted epidermis and pinpoint CD14/S100 signaling as a conserved pathway upregulated in dermatopatholo...
Article
Full-text available
Infection is a major source of complications in delayed diabetic wound healing. Increased understanding of differential bacterial responses to diabetic wounds will enable us to better understand chronic wound pathogenesis. Here we create delayed‐healing wounds infected with Staphylococcus aureus in non‐diabetic and diabetic mice and used RNA‐seq to...
Article
Background: Hypertrophic scars (HTS) result from injury to the skin and represent a clinical burden with limited treatment options. Previously, we demonstrated that statin drugs could attenuate HTS formation, but convenient topical delivery and retention of these drugs at the wound site remains a challenge. Aims: Here we aimed to develop a topic...
Article
Significance: Scar formation is a natural result of mammalian wound healing. In humans and other mammals, however, deep dermal wounds and thermal injuries often result in formation of hypertrophic scars, leading to substantial morbidity, and lending great importance to development of therapeutic modalities for burn scars. Clinical Issues: Thus, pr...
Article
Full-text available
Within an articulately characterized family of ion channels, the voltage-gated sodium channels, exists a black sheep, SCN7A (Nax). Nax, in contrast to members of its molecular family, has lost its voltage-gated character and instead rapidly evolved a new function as a concentration-dependent sensor of extracellular sodium ions and subsequent signal...
Article
Background: Skeletal muscle trauma can produce grave functional deficits, but therapeutic options remain limited. The authors studied whether a decellularized skeletal muscle scaffold would provide benefits in inducing skeletal muscle regeneration over acellular dermal matrices. Methods: Eighty-two rat muscle defects were surgically created and...
Article
Hypertrophic scar is an important clinical problem with limited therapeutic options. Aside from their roles as 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase inhibitors, statins have also been demonstrated to decrease scarring by reducing connective tissue growth factor (CTGF) expression. However, poor penetrative ability limits their utility as t...
Article
Background: Traumatic muscle loss often results in poor functional restoration. Skeletal muscle injuries cannot be repaired without substantial fibrosis and loss of muscle function. Given its regenerative properties, we evaluated outcomes of fetal tissue-derived decellularized matrix for skeletal muscle regeneration. We hypothesized that fetal mat...
Article
The sodium channel NaX (encoded by the SCN7A gene) was originally identified in the heart and skeletal muscle and is structurally similar to the other voltage‐gated sodium channels but does not appear to be voltage gated. Although NaX is expressed at high levels in cardiac and skeletal muscle, little information exists on the function of NaX in the...
Article
The skin plays a critical role in maintenance of water homeostasis. Dysfunction of the skin barrier causes not only delayed wound healing and hypertrophic scarring, but it also contributes to the development of various skin diseases. Dermatitis is a chronic inflammatory skin disorder that has several different subtypes. Skin of contact dermatitis a...
Article
Nax is an atypical sodium channel that mediates inflammatory pathways in pathological conditions of the skin. In this study, we developed a skin inflammation model in the rabbit ear through application of imiquimod (IMQ). Knockdown of Nax using RNAi attenuated IMQ‐induced skin inflammation, including skin erythema, scaling, and papule formation. Hi...
Article
MicroRNA-29 (miR-29) negatively regulates fibrosis and is downregulated in multiple fibrotic organs and tissues, including in the skin. miR-29 mimics prevent pulmonary fibrosis in mouse models but have not previously been tested in the skin. This study aimed to identify pharmacodynamic biomarkers of miR-29 in mouse skin, to translate those biomarke...
Article
Renal dysfunction has been associated with poor outcomes of wound healing in the diabetic population. The purpose of this study was to create an excisional wound healing model in diabetic mice with renal dysfunction to investigate the combined effects of diabetes and nephropathy on cutaneous ulcers. Renal impairment was introduced in diabetic db/db...
Article
Full-text available
Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of the epidermis, and dermal infiltration of inflammatory cells. Appropriate animal models that recapitulate human AD and allow the analysis of disease processes in a reliable manner are essential to the study...
Article
Disruption of the barrier function of skin increases transepidermal water loss (TEWL) and upregulates inflammatory pathways in the epidermis. Consequently, sustained expression of proinflammatory cytokines from the epidermis is associated with dermal scarring. We found increased expression of S100A12 in the epidermis of human hypertrophic and keloi...
Article
Full-text available
There is a growing interest in the development and evaluation of therapeutic agents that improve the cosmetic appearance of scars. Existing nonhuman animal models to study scarring, while valuable, have well-acknowledged limitations, as it is accepted that the biology of human scarring differs significantly from scarring in other species. Moreover,...
Article
Full-text available
Background We previously showed that intradermal injection of statins is a successful treatment for hypertrophic scarring. Topical application has many advantages over intradermal injection. In this study, we demonstrate the efficacy of topical statin treatment in reducing scar in our validated rabbit ear scar model. Methods Twenty New Zealand Whi...
Article
Background: Localized oxygen deficiency plays a central role in the pathogenesis of chronic wounds; thus, rectifying localized ischemia with oxygen therapy has been postulated to be an integral aspect of the management of chronic wounds. The efficacy of a novel approach for oxygen therapy on chronic wound healing was evaluated. Methods: Oxygen w...
Article
The mechanisms by which the epidermis responds to disturbances in barrier function and restores homeostasis are unknown. With a perturbation of the epidermal barrier, water is lost, resulting in an increase in extracellular sodium concentration. We demonstrate that the sodium channel Nax functions as a sodium sensor. With increased extracellular so...
Article
The most critical function of the epidermis is to prevent water loss and maintain skin homeostasis. Disruption of the functional skin barrier causes delayed wound healing, hypertrophic scarring, and many skin diseases. Herein, we show that reduced hydration increases the expression of S100 protein family members, S100A8/S100A9, in stratified kerati...
Article
Chronic wounds colonized with biofilm present a major burden to our healthcare system. While the current paradigm for wound healing is to maintain a moist environment, we sought to evaluate the effects of desiccation, and the ability of honey to desiccate wounds, on wound healing characteristics in Staphylococcus aureus biofilm wounds. In vivo biof...
Article
As the elderly population grows, so do the clinical and socioeconomic burdens of nonhealing cutaneous wounds, the majority of which are seen among persons over 60 years of age. Human studies on how aging effects wound healing will always be the gold standard, but studies have ethical and practical hurdles. Choosing an animal model is dictated by co...
Patent
This invention provides a method for reducing hypertropic scarring resulting from dermal wound healing in a subject in need which comprises administering to the subject an antisense oligonucleotide which inhibits expression of connective tissue growth factor (CTGF) in an amount effective to inhibit expression of CTGF and thereby reduce hypertrophic...
Article
Full-text available
Although it is known that the inflammatory response which results from disruption of epithelial barrier function after injury results in excessive scarring, the upstream signals remain unknown. It has also been observed that epithelial disruption results in reduced hydration status and that the use of occlusive dressings which prevent water loss fr...
Article
Background: Expander/implant breast reconstruction is a common approach to breast reconstruction. Although several studies evaluate risk factors for complications during the overall reconstructive process, no studies currently evaluate risk factors by stage of reconstruction. This information is important, as it can help guide physician and patien...
Article
Background aims: Adipocytes are metabolically active cells and have endocrine functions, such as cytokine secretion. Notably, adipocytes are found underneath skin and are thought to be involved in the body's response to ischemia-reperfusion (I-R). I-R injury is an important factor in the pathogenesis of chronic skin wounds. In this study, we inves...
Article
The importance of bacterial biofilms to chronic wound pathogenesis is well-established. Different treatment modalities, including topical dressings, have yet to demonstrate consistent efficacy against wound biofilm. This study evaluates the impact of a novel, anti-microbial Test Dressing on Pseudomonas aeruginosa biofilm-infected wounds. Six-mm der...
Article
Curcumin, a spice found in turmeric, is widely used in alternative medicine for its purported anti-inflammatory and antioxidant activities. The goal of this study was to test the curcumin efficacy on rabbit ear wounds under non-ischemic, ischemic, and ischemia reperfusion conditions. Previously described models of non-ischemic, ischemic, and ischem...
Article
Background: In 2002, an international advisory panel was convened to assess the scientific literature and develop evidence-based guidance for the prevention and treatment of pathologic scarring. Emerging clinical data, new treatment options, and technical advances warranted a renewed literature search and review of the initial advisory panel recom...
Article
Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation along multiple cell lineages and have potential applications in a wide range of therapies. These cells are commonly cultured as monolayers on tissue culture plastic but possibly lose their cell-specific properties with time in vitro. There is growing interest in culturing...
Article
Full-text available
Background Bacterial infections of wounds impair healing and worsen scarring. We hypothesized that transcriptome analysis of wounds infected with Klebsiella pneumoniae (K.p.) or Pseudomonas aeruginosa (P.a.) would indicate host-responses associated with the worse healing of P.a.- than K.p.-infected wounds. Methods Wounds created on post-operative...
Article
After studying this article, the participant should be able to: 1. Thoroughly recognize the factors that contribute to hematoma after face lift. 2. Describe and apply the current evidence for which technique gives superior results in outcomes after face lift. 3. Use the current evidence to determine whether to incorporate fibrin sealant into the pr...
Article
A common sequence for performing staged tissue expander breast reconstruction is to immediately insert a tissue expander, complete expansion before radiotherapy, and then perform the definitive reconstruction after radiotherapy is complete. This study evaluates the outcomes of this treatment regimen in 237 patients over a 10-year period at Northwes...
Article
Full-text available
Skin regeneration is an important area of research in the field of tissue-engineering, especially for cases involving loss of massive areas of skin, where current treatments are not capable of inducing permanent satisfying replacements. Human adipose-derived stem cells (ASC) have been shown to differentiate in-vitro into both mesenchymal lineages a...
Article
Following injury, Asian skin has a tendency towards hyper-pigmentation and scar formation, and therefore the prevention of scarring is particularly important in Asian patients. Since publication of an International Clinical Recommendation on Scar Management in 2002, there have been numerous publications in the field of scar management. Advances in...
Article
Full-text available
Encapsulated Klebsiella pneumoniae has emerged as one of the most clinically relevant and more frequently encountered opportunistic pathogens in combat wounds as the result of nosocomial infection. In this report, we show that imipenem displayed potent activity against established K. pneumoniae biofilms under both static and flow conditions in vitr...
Article
Mucosal wounds heal more rapidly, exhibit less inflammation, and are associated with minimal scarring when compared with equivalent cutaneous wounds. We previously demonstrated that cutaneous epithelium exhibits an exaggerated response to injury compared with mucosal epithelium. We hypothesized that treatment of injured skin with a semiocclusive dr...
Conference Paper
Introduction: The ideal aim of skin regeneration is to find a means to replace or regenerate this complex organ with normal appearance and with complete functionality. This process can be done in-vivo or in vitro and may require cells, natural or synthetic cell-supporting scaffold materials and bioactive molecules among other components. Unfortunat...
Article
Diabetic patients exhibit dysregulated inflammatory and immune responses that predispose them to chronic wound infections and the threat of limb loss. The molecular underpinnings responsible for this have not been well elucidated, particularly in the setting of wound biofilms. This study evaluates host responses in biofilm-impaired wounds using the...
Article
Full-text available
While the importance of oxygen to the wound healing process is well accepted, research and technological advances continue in this field and efforts are ongoing to further utilize oxygen as a therapeutic modality. In this paper, the authors briefly review the role of oxygen in wound healing and discuss the distinct mechanism of action as well as th...
Article
: Breast implant procedures are commonly performed using general anesthesia; however, patient apprehension, the potential for improved safety, lower costs, and faster recovery times have increased interest in the use of conscious sedation in plastic surgery. The authors examined the safety and efficacy of breast implant procedures performed under c...
Article
Bacterial biofilms, a critical chronic wound mediator, remain difficult to treat. Energy-based devices may potentially improve healing, but with no evidence of efficacy against biofilms. This study evaluates noncontact, low-frequency ultrasound (NLFU) in the treatment of biofilm-infected wounds. Six-millimeter dermal punch wounds in rabbit ears wer...
Article
Transforming growth factor-β (TGF-β) is a multifunctional growth factor involved in all aspects of wound healing. TGF-β accelerates wound healing, but an excess of its presence at the wound site has been implicated in pathological scar formation. Our group has recently identified CD109, a glycophosphatidylinositol-anchored protein, as a novel TGF-β...
Article
Although it is known that the inflammatory response that results from disruption of epithelial barrier function after injury results in excessive scarring, the upstream signals remain unknown. It has also been observed that epithelial disruption results in reduced hydration status and that the use of occlusive dressings that prevent water loss from...
Article
Objective: This study aimed to evaluate the effect of cyclic ischemia-reperfusion (IR) injury on wound healing using a novel rabbit ear model. Materials and methods: A lightweight clamp apparatus was developed for reversible occlusion of the central ear artery. Ventral ear wounds were analyzed postoperatively for epithelialization and granulatio...
Article
: Bacterial biofilms, which are critical mediators of chronic wounds, remain difficult to treat with traditional methods. Bacteriophage therapy against biofilm has not been rigorously studied in vivo. The authors evaluate the efficacy of a species-specific bacteriophage against Staphylococcus aureus biofilm-infected wounds using a validated, quanti...
Article
Full-text available
Multipotent mesenchymal stem cells (MSCs) are found in various tissues and can proliferate extensively in vitro. MSCs have been used in preclinical animal studies and clinical trials in many fields. Adipose derived stem cells (ASCs) have several advantages compared to other MSCs for use in cell-based treatments because they are easy to isolate with...
Data
Schematic drawing of rabbit wounds and histological analysis. EG, epithelial gap; GA, granulation area. (PDF)
Data
Full-text available
Histological quantification of ASCs treated wounds. 1×105 ASCs were delivered to 7 mm wounds on one ear and 3×104 ASCs were delivered to wounds on the contralateral ear of rabbits. Wounds were harvested at POD7 and epithelial gap (A) and granulation tissue area (B) were measured (n = 11 for 1×105 ASCs & n = 12 for 3×104 ASCs). N represents the tota...
Data
Full-text available
Comparison of the effect of ASCs, BM-MSCs, and DFs on wound repair. The granulation tissue measurement data at POD7 wounds in Figure 3 was re-analyzed by the ANOVA with post-hoc analysis. Number of wounds analyzed; n = 69 for saline, n = 20 for BM-MSCs, n = 36 for ASCs, n = 24 for DFs. N represents the total number of wounds from fourteen (saline),...
Data
Full-text available
Analysis of α-SMA expressing cells in wounds. Chicken anti-GFP and mouse anti-α-SMA antibodies were used to detect GFP and α-SMA. Nuclei were stained with DAPI. GFP (A, D, G), α-SMA (B, E, H), and merged (C, F, I) images in Figure 4E, 4F, 4G were shown. Endogenous cells and transplanted ASCs which express α-SMA showed red and yellow color, respecti...
Data
Full-text available
Measurement of epithelial gap of ASCs treated wounds. A total of 1×105 ASCs were delivered to 7 mm wounds on one ear. In the contralateral ear, PBS alone was delivered as a control. Wounds were harvested at POD7 and epithelial gap was measured. Data shown as mean + SEM. n = 35 for saline & n = 36 for ASCs. N represents the total number of wounds fr...
Data
Full-text available
Western blot analysis for surface markers of rabbit BM-MSCs. Whole cell extract of rabbit BM-MSCs from P1 to P9 was prepared and loaded 20 µg per well. The expression of CD29, CD44, CD90, and CD105 were detected with their specific antibodies as indicated. β-actin was detected as a loading control. (PDF)