Publications by authors named "Robert D Galiano"

110 Publications

Functional Properties of a Purified Reconstituted Bilayer Matrix Design Support Natural Wound Healing Activities.

Plast Reconstr Surg Glob Open 2021 May 21;9(5):e3596. Epub 2021 May 21.

Professional Education and Research Institute, Roanoke, Va.

Biomaterial engineering has produced numerous matrices for use in tissue repair, utilizing various materials and processing methods, which can impact the ability of the products to encourage wound healing. Recently, we observed favorable clinical outcomes, using a novel purified reconstituted bilayer matrix (PRBM; Geistlich Derma-Gide) to treat chronic diabetic foot ulcers.

Methods: Evaluations of the structural and functional characteristics of PRBM in vitro were performed to assess how this biomaterial may affect the favorable clinical results observed by influencing the wound environment and key physiologic mechanisms necessary for the healing process. Investigations included scanning electron microscopy, cell culture analyses, gene expression assays, matrix metalloproteinase activity assessment, and pH measurement.

Results: Cross-sectional scanning electron microscopy demonstrated a distinct bilayer structure with porous and compact layers. The PRBM structure allowed cell types involved in wound healing to bind and proliferate. Expression analysis of growth factor-responsive genes demonstrated binding and preservation of bioactive growth factors TGF-β1, bFGF, and VEGF by PRBM. Boyden chamber migration assays revealed increased cellular migration compared with controls. In the presence of PRBM, the activity of MMP-1, MMP-2, and MMP-9 was significantly lower compared with control samples. pH of the PRBM in solution was slightly acidic.

Conclusions: Based on in vitro evaluations, it appears that the PRBM processing without deleterious chemical crosslinking results in a suitable ECM possessing characteristics to aid natural wound healing, including cell attachment, migration, proliferation, differentiation, and angiogenesis. These in vitro data support the promising healing rate observed clinically when chronic DFUs are treated with PRBM.
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http://dx.doi.org/10.1097/GOX.0000000000003596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140771PMC
May 2021

Daily Quality-of-life Impact of Scars: An Interview-based Foundational Study of Patient-reported Themes.

Plast Reconstr Surg Glob Open 2021 Apr 15;9(4):e3522. Epub 2021 Apr 15.

Division of Plastic and Reconstructive Surgery, Northwestern University, Chicago, Ill.

Background: Scars negatively impact mental health. Prior patient interview studies on cutaneous scars have elicited opinions pertaining to psychosocial effects, appearance, and symptoms. There remains a need for patient-reported opinions in broader contexts, including career and sexual well-being, to better understand patients' experiences with their cutaneous scars.

Methods: In this qualitative study, patients with cutaneous scars participated in semi-structured interviews. Transcripts were analyzed using a constant comparative approach using the data software QDAMiner, to generate a thematic framework encompassing patients' experience with cutaneous scars.

Results: In total, 37 patients aged 25-79 years (mean 45, SD 17.9) were interviewed. Patients presented with keloid (2/37, 5%), hypertrophic (5/37, 14%), atrophic (4/37, 11%), and linear surgical (18/37, 49%) scars. Opinions fell under 8 overarching themes. Patients spoke commonly about psychological and social well-being (references to the frequency of thinking about a scar and talking about scars with others were mentioned 56 times by 26 patients and 103 times by 29 patients, respectively, for example). Discussions of sexual well-being and career were elicited but rarer (references to feeling uncomfortable when naked and negative impacts on professional networking were mentioned 17 times by 7 patients and 5 times by 3 patients, respectively, for example).

Conclusions: The relationship between determinants of patients' opinions of their scars and their impact on quality-of-life is complex. These results expand upon the existing knowledge of the effects scars have on quality-of-life and can contribute to the development and validation of future scar outcome measures.
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http://dx.doi.org/10.1097/GOX.0000000000003522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049395PMC
April 2021

Which Resources Are Better: Sales or Scholarly? An Assessment on the Readability, Quality, and Technical Features of Online Chemical Peel Websites.

Aesthet Surg J Open Forum 2021 Jan 4;3(1):ojab008. Epub 2021 Mar 4.

Department of Surgery, Division of Plastic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Background: Chemical peels are an exceedingly popular cosmetic treatment with a wide variety of suppliers, each with its own online health resource describing the procedure. With increasing reliance on the internet for medical information, it is crucial that these resources provide reliable information for patients to make informed decisions.

Objectives: The aim of this study was to examine popular chemical peel resources and determine if those that offered chemical peel treatments (Sales) had lower readability, quality of information, and technical features compared with those that did not (Scholarly).

Methods: The term "chemical peel" was searched in July 2020 and the top 50 websites were retrieved for analysis. Each resource's readability, quality, and technical features were measured through 8 readability formulas, the DISCERN and Health on the Net Code (HONcode), and 2 website performance monitors.

Results: The 50 websites were analyzed with an average Fry readability score of 13th grade. Scholarly websites displayed higher readability than Sales (Flesch Reading Ease 54.4 > 47.4, = 0.047 and Coleman-Liau Index 10.6 < 11.7, = 0.04). Scholarly resources surpassed Sales both in quality (DISCERN 56.4 > 39.7, < 0.001 and HONcode 11.8 > 9.5, = 0.032) and technical features (WooRank 76.9 > 68.6, = 0.0082).

Conclusions: The average readability of chemical peel resources is too difficult, and their quality must be improved. Scholarly resources exhibited higher readability, quality, and technical features than Sales websites.
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http://dx.doi.org/10.1093/asjof/ojab008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011339PMC
January 2021

The Use of Botulinum Toxin to Prevent Anastomotic Thrombosis and Promote Flap Survival: A Bridge to Developing Clinical Studies.

Ann Plast Surg 2021 Jan 19. Epub 2021 Jan 19.

From the Division of Plastic and Reconstructive Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL.

Background: Despite the possibility of using botulinum toxin to improve perfusion and prevent vasospasm, only a few studies have examined the use of botulinum toxin in the setting of flap surgery and thrombosis, and the mechanisms have not been fully explained.

Objective: The primary objective of this study was to provide a comprehensive review of the effectiveness of botulinum toxin in anastomotic thrombosis prevention and surgical flap survival to determine the value of conducting large-scale human trials.

Methods: Using the SYRCLE and CAMRADES criteria, a systematic review was performed. PubMed, Medline, EmBase, and the Cochrane Library were searched for studies that met our eligibility criteria.

Results: Twenty studies were included in the final selection. A total of 397 subjects were included. Eighteen studies used botulinum toxin type A alone, one used botulinum toxin type B alone, and only one used both botulinum toxin type A and botulinum toxin type B. The most commonly used injection technique was a preoperative intradermal injection. The most common procedure performed was a pedicled flap with random pattern skin flaps (65%). The mean injection dose was 28.17 ± 49.21 IU, whereas the mean reported injection time for studies using animal models was 7.4 ± 6.84 days.

Conclusions: Similar mechanisms demonstrated in animal models may be replicable in humans, allowing botulinum toxin to be used to prolong flap survival. However, many factors, such as optimal injection techniques, dosages, and long-term outcomes of botulinum use in flap surgery, need to be further assessed before applying this to clinical practice.
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http://dx.doi.org/10.1097/SAP.0000000000002666DOI Listing
January 2021

Open-label Venous Leg Ulcer Pilot Study Using a Novel Autolologous Homologous Skin Construct.

Plast Reconstr Surg Glob Open 2020 Jul 16;8(7):e2972. Epub 2020 Jul 16.

The Professional Education and Research Institute (PERI), Roanoke, Va.

Venous leg ulcers (VLUs) are often refractory to compression therapy, and their prevalence is increasing. An autologous homologous skin construct (AHSC) that uses the endogenous regenerative capacity of healthy skin has been developed to treat cutaneous defects, with a single application. The ability of AHSC to close VLUs with a single treatment was evaluated in an open-label, single-arm feasibility study to test the hypothesis that AHSC treatment will result in wound closure by providing healthy autologous tissue to the wound bed.

Methods: Ten VLUs were treated with a single application of AHSC. A 1.5 cm full-thickness skin harvest from the proximal calf was collected and sent to a Food and Drug Administration-registered facility, where it was processed into AHSC and returned to the provider within 48 hours. AHSC was spread evenly across the wound and dressed with silicone. The primary endpoint was wound closure rate at 12 weeks. Wound closure was followed with 3-dimensional planimetry, and closure was confirmed by a panel of plastic surgeons. Additional endpoints followed for 12 weeks included graft take, harvest site closure, adverse event rate, complications, and patient-reported pain.

Results: All 10 VLUs demonstrated successful graft take as evidenced by graft persisting in wound and harvest site closure. Eight VLUs exhibited complete closure within 12 weeks. One VLU that failed to heal with a prior split thickness skin graft closed within 13.5 weeks with AHSC. The mean time of closure was 34 days (95% confidence interval, 14-53). Pain improved by closure confirmation visit. There was 1 serious adverse event unrelated to the product or procedure.

Conclusion: This pilot study demonstrated that AHSC may be a viable single-application topical intervention for VLUs and warrants further investigation in larger, controlled studies.
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http://dx.doi.org/10.1097/GOX.0000000000002972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413806PMC
July 2020

Allogeneic Decellularized Muscle Scaffold Is Less Fibrogenic and Inflammatory than Acellular Dermal Matrices in a Rat Model of Skeletal Muscle Regeneration.

Plast Reconstr Surg 2020 07;146(1):43e-53e

From the Laboratory for Tissue Repair and Regenerative Surgery and the Division of Plastic and Reconstructive Surgery, Northwestern University, Feinberg School of Medicine.

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 assigned to no intervention or implantation of AlloDerm, Strattice, decellularized rat muscle, or decellularized rat dermis to 30 or 60 days. Decellularized rat muscle and dermis were prepared using a negative pressure-assisted protocol. Assessment for cellularity, neovascularization, myogenesis, inflammation and fibrosis were done histologically and by polymerase chain reaction.

Results: Histology showed relative hypercellularity of AlloDerm (p < 0.003); Strattice appeared encapsulated. Immunofluorescence for CD31 and myosin heavy chain in decellularized rat muscle revealed dense microvasculature and peripheral islands of myogenesis. MyoD expression in muscle scaffolds was 23-fold higher than in controls (p < 0.01). Decellularized rat muscle showed no up-regulation of COX-2 (p < 0.05), with less expression than decellularized rat dermis and Strattice (p < 0.002). Decellularized rat muscle scaffolds expressed tumor necrosis factor-α less than Strattice, AlloDerm, and decellularized rat dermis (p < 0.01); collagen-1a less than decellularized rat dermis and Strattice (p < 0.04); α-smooth muscle actin 7-fold less than AlloDerm (p = 0.04); and connective tissue growth factor less than Strattice, AlloDerm, and decellularized rat dermis (p < 0.02).

Conclusion: Decellularized muscle matrix appears to reduce inflammation and fibrosis in an animal muscle defect as compared with dermal matrices and promotes greater expression of myocyte differentiation-inducing genes.
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http://dx.doi.org/10.1097/PRS.0000000000006922DOI Listing
July 2020

Up-to-date role of the dehydrated human amnion/chorion membrane (AMNIOFIX) for wound healing.

Expert Opin Biol Ther 2020 10 20;20(10):1125-1131. Epub 2020 Jul 20.

Division of Plastic and Reconstructive Surgery, Department of General Surgery, Northwestern University , Chicago, IL, USA.

Introduction: Chronic wounds pose a significant burden on patients, society, and the health-care setup. Higher costs, protracted clinical course, and increased risk of complications necessitate identifying novel treatment modalities that hasten healing and wound closure.

Areas Covered: This article covers newer available treatment modalities for chronic wounds, namely the dehydrated amniotic membrane products, biological skin substitutes, and similar therapies aimed at the healing of chronic non-healing wounds. It presents product description for Amniofix (dehydrated human amniotic/chorionic membrane) and its efficacy, compared to other similar products.

Expert Opinion: In our experience and review of available literature, we expect Amniofix to offer wound care specialists with a more effective, easy-to-use, and convenient treatment modality for chronic wounds. Amniofix and other dHACM (dehydrated human amniotic/chorionic membrane) therapies reported faster and complete healing with lower complication rates, when compared to other similar products. These features encourage the use of Amniofix in Diabetic foot ulcers and Venous Leg Ulcers, besides other conditions such as plantar fasciitis.
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http://dx.doi.org/10.1080/14712598.2020.1787979DOI Listing
October 2020

The impact of negative-pressure wound therapy with instillation on wounds requiring operative debridement: Pilot randomised, controlled trial.

Int Wound J 2020 Oct 21;17(5):1194-1208. Epub 2020 Jun 21.

Department of Plastic Surgery, MedStar Georgetown University Hospital, Washington, District of Columbia, USA.

Presence of bacteria in wounds can delay healing. Addition of a regularly instilled topical solution over the wound during negative-pressure wound therapy (NPWT) may reduce bioburden levels compared with standard NPWT alone. We performed a prospective, randomised, multi-centre, post-market trial to compare effects of NPWT with instillation and dwell of polyhexamethylene biguanide solution vs NPWT without instillation therapy in wounds requiring operative debridement. Results showed a significantly greater mean decrease in total bacterial counts from time of initial surgical debridement to first dressing change in NPWT plus instillation (n = 69) subjects compared with standard NPWT (n = 63) subjects (-0.18 vs 0.6 log CFU/g, respectively). There was no significant difference between the groups in the primary endpoint of required inpatient operating room debridements after initial debridement. Time to readiness for wound closure/coverage, proportion of wounds closed, and incidence of wound complications were similar. NPWT subjects had 3.1 times the risk of re-hospitalisation compared with NPWT plus instillation subjects. This study provides a basis for exploring research options to understand the impact of NPWT with instillation on wound healing.
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http://dx.doi.org/10.1111/iwj.13424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540575PMC
October 2020

Decellularized Fetal Matrix Suppresses Fibrotic Gene Expression and Promotes Myogenesis in a Rat Model of Volumetric Muscle Loss.

Plast Reconstr Surg 2020 09;146(3):552-562

From the Division of Plastic and Reconstructive Surgery, Northwestern University, Feinberg School of Medicine; the Division of Plastic and Reconstructive Surgery, University of Chicago Medicine; and the Division of Plastic and Reconstructive Surgery, Université de Montréal.

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, the authors evaluated outcomes of fetal tissue-derived decellularized matrix for skeletal muscle regeneration. The authors hypothesized that fetal matrix would lead to enhanced myogenesis and suppress inflammation and fibrosis.

Methods: Composite tissue composed of dermis, subcutaneous tissue, and panniculus carnosus was harvested from the trunk of New Zealand White rabbit fetuses on gestational day 24 and from Sprague-Dawley rats on gestational day 18 and neonatal day 3, and decellularized using a sodium dodecyl sulfate-based negative-pressure protocol. Six, 10-mm-diameter, full-thickness rat latissimus dorsi wounds were created for each treatment, matrix was implanted (excluding the defect groups), and the wounds were allowed to heal for 60 days. Analyses were performed to characterize myogenesis, neovascularization, inflammation, and fibrosis at harvest.

Results: Significant myocyte ingrowth was visualized in both allogeneic and xenogeneic fetal matrix groups compared to neonatal and defect groups based on myosin heavy chain immunofluorescence staining. Microvascular networks were appreciated within all implanted matrices. At day 60, expression of Ccn2, Col1a1, and Ptgs2 were decreased in fetal matrix groups compared to defect. Neonatal matrix-implanted wounds failed to show decreased expression of Col1a1 or Ptgs2, and demonstrated increased expression of Tnf, but also demonstrated a significant reduction in Ccn2 expression.

Conclusions: Initial studies of fetal matrices demonstrate promise for muscle regeneration in a rat latissimus dorsi model. Further research is necessary to evaluate fetal matrix for future translational use and better understand its effects.
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http://dx.doi.org/10.1097/PRS.0000000000007093DOI Listing
September 2020

Liposome-encapsulated statins reduce hypertrophic scarring through topical application.

Wound Repair Regen 2020 07 19;28(4):460-469. Epub 2020 May 19.

Laboratory for Tissue Repair and Regenerative Surgery, Division of Plastic and Reconstructive Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

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 topical treatments for hypertrophic scar. Here, we aim to develop novel statin formulations using liposomes to enhance dermal penetrative ability and to evaluate their efficacy against formation of hypertrophic scar utilizing our validated rabbit ear hypertrophic scar model. Liposomal simvastatin or pravastatin were compounded using a novel, flexible liposomal formulation and applied topically to rabbit ear hypertrophic scars daily from postoperation day (POD) 14 until POD 25. Scar color, including erythema and melanin, was measured using reflectance spectrophotometry on POD 28, and scar tissue was harvested for evaluation of scar elevation index as well as gene and protein expression. Human foreskin fibroblasts were also treated with statin formulations and CCN2 expression was determined by quantitative PCR. Both simvastatin and pravastatin were efficiently encapsulated in liposomes, forming nanometer-scale particles possessing highly negative charges. Topical treatment with liposomal simvastatin and pravastatin at 6.5% concentration significantly reduced scar elevation index and decreased type I/III collagen content and myofibroblast persistence in the wound. The erythema/vascularity of scars was reduced by liposomal statin treatment, with concomitant decrease of CD31 expression as measured histologically. Expression levels of transcripts encoding CTGF, collagen I, and collagen III collagen in scar tissue were also decreased by liposomal pravastatin treatment, as were myofibroblast persistence and the type I/III collagen ratio as assessed by immunofluorescence and picrosirus red staining, respectively. Treatment of human foreskin fibroblasts with simvastatin or with liposome-encapsulated pravastatin resulted in decreased expression of transcript encoding CTGF. Overall, our novel statin formulations encapsulated in liposomes were successfully delivered through topical application, significantly reducing hypertrophic scarring in a rabbit ear model.
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http://dx.doi.org/10.1111/wrr.12811DOI Listing
July 2020

The Northwestern Abdominoplasty Scar Model: A Tool for High-Throughput Assessment of Scar Therapeutics.

Adv Wound Care (New Rochelle) 2020 07 29;9(7):396-404. Epub 2020 Apr 29.

Department of Plastic and Reconstructive Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Scar management is an important concern in plastic surgery. Scar models that best mimic human scarring are essential for understanding scar development and progression, assessing the efficacy of therapeutics, and providing reliable and valid research outcomes. In 2016, Lanier proposed a new patient model, the Northwestern Abdominoplasty Scar Model, that overcomes the prior limitations of both animal and human models, with greater representativeness of the human scarring process, expedited recruitment, smaller sample requirements, and greater flexibility in the types and number of interventions that can be studied simultaneously. Existing animal models suffer from limitations that impede generalization to human scars. Human scar studies are difficult to conduct and rarely used due to recruitment difficulties, ethical concerns regarding purposeful wounding, and inherent variability based on location, type of scar, and the heterogeneity of the host response between humans. Although overcoming many of these hurdles, the Northwestern Abdominoplasty Scar Model still has a few limitations. In addition, there remains a need for further study of and comparison between the Northwestern Abdominoplasty Scar Model and existing human and animal models, to inspire more widespread acceptance of a standardized human scar model. The Northwestern Abdominoplasty Scar Model is a critical stepping stone toward better human scar models. This model hopefully will inspire other patient models utilizing elective surgery to overcome recruitment and ethical concerns.
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http://dx.doi.org/10.1089/wound.2018.0900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307678PMC
July 2020

An observational pilot study using a purified reconstituted bilayer matrix to treat non-healing diabetic foot ulcers.

Int Wound J 2020 Aug 7;17(4):966-973. Epub 2020 Apr 7.

Professional Education and Research Institute, Roanoke, Virginia, USA.

Diabetic foot ulcers (DFUs) have significant clinical impact and carry a substantial economic burden. Patients with DFUs that are refractory to standard wound care are at risk for major complications, including infection and amputation and have an increased risk of mortality. This study evaluated the safety and preliminary efficacy of a novel decellularised purified reconstituted bilayer matrix (PRBM) in treating DFUs. Ten diabetic patients with refractory wounds that failed to heal after at least 4 weeks of standard wound care were studied in this Institutional Review Board approved trial. Ten consecutive wounds were treated weekly with the PRBM for up to 12 weeks. At each weekly visit, the wound was evaluated, photographed, and cleaned, followed by application of new graft if not completely epithelialised. Assessment included measurement of the wound area and inspection of the wound site for signs of complications. The primary outcome measure was wound closure, as adjudicated by independent reviewers. Secondary outcomes included assessment of overall adverse events, time to closure, percent area reduction, and the cost of product(s) used. Nine of 10 patients achieved complete wound closure within 4 weeks, and 1 did not heal completely within 12 weeks. The mean time to heal was 2.7 weeks. The mean wound area reduction at 12 weeks was 99%. No adverse events nor wound complications were observed. These early clinical findings suggest that the PRBM may be an effective tool in the treatment of diabetic foot ulcers.
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http://dx.doi.org/10.1111/iwj.13353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384195PMC
August 2020

Knockdown of sodium channel Na reduces dermatitis symptoms in rabbit skin.

Lab Invest 2020 05 10;100(5):751-761. Epub 2020 Jan 10.

Laboratory for Tissue Repair and Regenerative Surgery, Department of Surgery/Plastic Surgery Division, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.

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 and atopic dermatitis (AD) show epidermal barrier dysfunction. Na is a sodium channel that regulates inflammatory gene expression in response to perturbation of barrier function of the skin. We found that in vivo knockdown of Na using RNAi reduced hyperkeratosis and keratinocyte hyperproliferation in rabbit ear dermatitic skin. Increased infiltration of inflammatory cells (mast cells, eosinophils, T cells, and macrophages), a characteristic of dermatitis, was reduced by Na knockdown. Upregulation of PAR-2 and thymic stromal lymphopoietin (TSLP), which induce Th2-mediated allergic responses, was inhibited by Na knockdown. In addition, expression of COX-2, IL-1β, IL-8, and S100A9, which are downstream genes of Na and are involved in dermatitis pathogenesis, were also decreased by Na knockdown. Our data show that knockdown of Na relieved dermatitis symptoms in vivo and indicate that Na is a novel therapeutic target for dermatitis, which currently has limited therapeutic options.
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http://dx.doi.org/10.1038/s41374-020-0371-1DOI Listing
May 2020

Complex Lower Extremity Wound in the Complex Host: Results From a Multicenter Registry.

Plast Reconstr Surg Glob Open 2019 Apr 11;7(4):e2129. Epub 2019 Apr 11.

Department of Plastic Surgery, University of Texas Southwestern, Dallas, Tex.

Background: The complex diabetic lower extremity wound has not been well studied. There are a variety of new technologies now being applied with a paucity of evidence in evaluating their outcomes. The aim of this study is to describe clinical outcomes in the complex lower extremity wound in the comorbid host. We hypothesized that treatment choice would have minimal impact on healing outcomes in this compromised population.

Methods: A multicenter retrospective registry of patients with diabetes and lower extremity wounds was created to compare treatment modalities of collagen-glycosaminoglycan scaffold, negative-pressure wound therapy, local tissue flap, and free tissue transfer. Statistical analyses included descriptive, proportional comparisons and Cox regression.

Results: There were no statistical differences in age, hemoglobin A1c, or body mass index between groups. Study patients had a history of amputation (40.5%), peripheral vascular disease (54.6%), peripheral neuropathy (64.8%), end-stage renal disease (13.9%), renal/hepatic disease (40.4%), and hypertension (85%). The most common wound etiologies were surgical dehiscence (69%), diabetic neuropathic wounds (39%), and ischemic wounds (28%), most commonly located on the foot or at a prior amputation site (30%). Mean wound area was 57.9 cm and almost half with exposed bone. There were no statistical differences between treatment groups in proportion or time to healing, recurrence, or time to return to baseline function.

Conclusions: Commonly used treatment modalities employed for this population of patients resulted in similar outcomes. This is the first study to describe the complex diabetic lower extremity wound in a complex host.
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http://dx.doi.org/10.1097/GOX.0000000000002129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554184PMC
April 2019

A prospective, randomised controlled trial evaluating the effectiveness of the fluid immersion simulation system vs an air-fluidised bed system in the acute postoperative management of pressure ulcers: A midpoint study analysis.

Int Wound J 2019 Aug 7;16(4):989-999. Epub 2019 May 7.

Division of Plastic and Reconstructive Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

The use of pressure-offloading support surfaces is considered the standard of care for pressure ulcers (PUs) by most surgeons. The fluid immersion simulation system (FIS) has shown significant results in previous studies. We compared it, for the first time, with a representative air-fluidised bed (AFB) for outcomes related to post-surgical flap closures. This trial was performed over 25 months, in which 40 subjects between 18 and 85 years of age with ≤2 PUs and history of <3 surgical closures underwent reconstruction by one surgeon. Subjects were randomly assigned to either treatment group for 2 weeks after closure. The primary endpoint was success of closure after the study period. Secondary endpoints included incidence of complications and nursing and patient acceptability of the device. The FIS group included 19 subjects, and the AFB group included 21. Flap failure rate was similar between groups (15% vs 17%; P = .99). The Minor complications rate, particularly dehiscence, was higher in the FIS group (66.7% vs 15%; P = .02). Nurse and patient self-reported acceptability had better mean numeric scores in the FIS compared with AFB (nurse: 1.5 vs 1.9; P = .12; patient: 1.9 vs 2.2; P = .14). Further analysis will be conducted to gain better insight on the FIS as an alternative treatment for PUs.
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http://dx.doi.org/10.1111/iwj.13133DOI Listing
August 2019

Imiquimod-induced skin inflammation is relieved by knockdown of sodium channel Na.

Exp Dermatol 2019 05;28(5):576-584

Department of Surgery/Plastic Surgery Division, Laboratory for Tissue Repair and Regenerative Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illionis.

Na 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 Na using RNAi attenuated IMQ-induced skin inflammation, including skin erythema, scaling and papule formation. Histologic analysis showed that thickening and insufficient differentiation of the epidermis found in psoriasis-like skin were normalized by administration of Na -RNAi. Excessive infiltration of inflammatory cells found in inflammatory lesions, such as mast cells, eosinophils, neutrophils, T cells and macrophages, was reduced by Na -RNAi. Expression of S100A9, which is a downstream gene of Na and a mediator of inflammation, was decreased by Na -RNAi. Our results demonstrated that knockdown of Na ameliorated IMQ-induced psoriasis-like skin inflammation in vivo. Thus, targeting of Na may represent a potential therapeutic option for the treatment of psoriasis.
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http://dx.doi.org/10.1111/exd.13917DOI Listing
May 2019

Renal dysfunction aggravated impaired cutaneous wound healing in diabetic mice.

Wound Repair Regen 2019 01 4;27(1):49-58. Epub 2018 Dec 4.

Division of Plastic and Reconstructive Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

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 mice through unilateral nephrectomy and electrocoagulation of the contralateral kidney. Renal function was subsequently monitored with assays of blood urea nitrogen and spot urinary protein/creatinine ratio. After 8 weeks, splinted, full-thickness excisional wounds were created on the dorsal skin and harvested on postoperative days 7 and 14 for further evaluation of wound healing. Renal injury promoted the increase of blood urea nitrogen 3 weeks after initial operation, which was maintained at double the control level throughout the study, concomitantly leading to a significant increase of spot urinary protein excretion. Diabetic mice with renal injury displayed notably impaired wound healing processes, concurrent with reductions in cellular proliferation and angiogenesis, as well as increases in M1 polarized macrophages, infiltrated neutrophils, oxidative stress, and cellular apoptosis. Furthermore, quantitative polymerase chain reaction (qPCR) results displayed corresponding changes of related genes (TNF-α, IL-1β, SOD2) in the wounds of renal injured db/db mice. Renal manipulation in this study accelerated the progress of renal impairment, which was demonstrated to aggravate impaired cutaneous wound healing in diabetic mice.
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http://dx.doi.org/10.1111/wrr.12682DOI Listing
January 2019

Anti-CTGF Oligonucleotide Reduces Severity of Postsurgical Hypertrophic Scars in a Randomized, Double-Blind, Within-Subject, Placebo-Controlled Study.

Plast Reconstr Surg 2018 08;142(2):192e-201e

From Excaliard Pharmaceuticals; PRA International-KCI; the Jewell Plastic Surgery Center; Connall Cosmetic Surgery; Miller Cosmetic Surgery at Scripps Hospital; the Division of Plastic Surgery, Northwestern University; and Body Aesthetic Plastic Surgery.

Background: Connective tissue growth factor (CTGF) levels are up-regulated in wounded skin and are thought to play a major role in scar formation. An antisense oligonucleotide targeting CTGF was evaluated in adult patients undergoing hypertrophic scar revision surgery, to determine effects on reducing the severity of subsequent scars.

Methods: In a randomized, double-blind, within-subject, placebo-controlled study, 23 female subjects (aged 28 to 55 years) with bilateral, symmetric, hypertrophic surgical scars of the breast underwent scar revision surgery. The resulting breast incisions were randomized to receive EXC 001 (5 mg/cm) or placebo injected intradermally at postsurgery weeks 2, 5, 8, and 11. Scar severity assessments were performed at weeks 12 and 24 by an expert panel using blinded photographs, and by physicians and subjects using a scar scoring scale, the Patient and Observer Scar Assessment Scale. An assumption of the design is that within-subject variance would be small and that whatever within-subject variance there was would be controlled through the randomization process.

Results: EXC 001 significantly reduced scar severity at both 12 and 24 weeks after scar revision surgery in all three measures (expert panel and physician Patient and Observer Scar Assessment Scale, p < 0.001; Patient and Observer Scar Assessment Scale, p < 0.003).

Conclusions: This study provided positive preliminary data that intradermal injection of EXC 001 produced a significant reduction in severity of postsurgical skin scars, as measured by physicians, subjects, and an expert panel. This study provided evidence that suppression of CTGF could be a viable strategy for hypertrophic scar reduction therapy and that further study of the antisense oligonucleotide EXC 001 was indicated.

Clinical Question/level Of Evidence: Therapeutic, II.
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http://dx.doi.org/10.1097/PRS.0000000000004590DOI Listing
August 2018

Use of an aseptically processed, dehydrated human amnion and chorion membrane improves likelihood and rate of healing in chronic diabetic foot ulcers: A prospective, randomised, multi-centre clinical trial in 80 patients.

Int Wound J 2018 Dec 17;15(6):950-957. Epub 2018 Jul 17.

Professional Education and Research Institute, Roanoke, Virginia.

Amnion and chorion allografts have shown great promise in healing diabetic foot ulcers (DFUs). Results from an interim analysis of 40 patients have demonstrated the accelerated healing ability of a novel aseptically processed, dehydrated human amnion and chorion allograft (dHACA). The goal of this study was to report on the full trial results of 80 patients where dHACA was compared with standard of care (SOC) in achieving wound closure in non-healing DFUs. After a 2-week screening period, during which patients with DFUs were unsuccessfully treated with SOC, patients were randomised to either SOC alone or SOC with dHACA applied weekly for up to 12 weeks. At 12 weeks, 85% (34/40) of the dHACA-treated DFUs healed, compared with 33% (13/40) treated with SOC alone. Mean time to heal within 12 weeks was significantly faster for the dHACA- treated group compared with SOC, 37 days vs 67 days in the SOC group (P = .000006). Mean number of grafts used per healed wound during the same time period was 4.0, and mean cost of the tissue to heal a DFU was $1771. The authors concluded that aseptically processed dHACA heals DFUs significantly faster than SOC at 12 weeks.
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http://dx.doi.org/10.1111/iwj.12954DOI Listing
December 2018

Incisional Negative Pressure Wound Therapy for Prevention of Wound Healing Complications Following Reduction Mammaplasty.

Plast Reconstr Surg Glob Open 2018 Jan 12;6(1):e1560. Epub 2018 Jan 12.

Feinberg School of Medicine, Chicago, Ill.; University of Cape Town, Cape Town, South Africa; Montefiore Medical Center, New York, N.Y.; Maastricht University Medical Centre, Maastricht, The Netherlands; Cleveland Clinic, Cleveland, Ohio; University of Nantes, Nantes, France; Smith & Nephew Wound Management, Inc., Fort Worth, Tex.; and Smith & Nephew Wound Management Ltd, Hull, United Kingdom.

Background: It has been proposed that negative pressure wound therapy (NPWT) applied prophylactically to a closed incision may decrease the incidence of wound complications. Patients undergoing reduction mammaplasty are at risk of wound complications such as delayed healing, infection, and dehiscence, and the bilateral nature of the surgery allows for a within-patient randomized study to evaluate incisional NPWT's effect in reducing healing complications.

Methods: In this multicenter trial, 200 patients undergoing bilateral reduction mammaplasty were treated with PICO Single-Use NPWT System or standard wound-care dressings randomized to right or left breast for up to 14 days to enable within-patient comparison. Follow-up assessments were conducted to evaluate the difference in incision healing complications up to 21 days postsurgery. Healing complications (for the primary endpoint) were defined as delayed healing (incision not 100% closed by 7 days) and occurrence of dehiscence or infection within 21 days. Individual healing complications were assessed separately as secondary endpoints.

Results: Significantly fewer healing complications (primary endpoint) were noted in NPWT-treated breasts [113 (56.8%)] versus standard care [123 (61.8%)]. The difference of 10 (5.0%) patients with fewer healing complications using NPWT was statistically significant ( = 0.004). NPWT also resulted in a significantly lower incidence of dehiscence (secondary endpoint) compared with standard care [32 patients (16.2%) versus 52 patients (26.4%)] by day 21, a relative reduction of 38% ( < 0.001).

Conclusions: This is the first major prospective, within-patient, randomized, controlled, multicenter study to provide evidence for an incisional NPWT strategy to reduce healing complications.
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http://dx.doi.org/10.1097/GOX.0000000000001560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811280PMC
January 2018

Does noncontact low-frequency ultrasound therapy contribute to wound healing at the molecular level?

Wound Repair Regen 2017 09 8;25(5):871-882. Epub 2017 Dec 8.

Center for Wound Healing, South Shore Hospital, Weymouth, Massachusetts.

Noncontact low-frequency ultrasound (NLFU) is used to treat various types of chronic wounds including venous, diabetic, and pressure ulcers. The objective for this substudy of the IN BALANCE RCT VLU trial was to characterize and compare the NLFU treatment group and patients receiving standard of care (SOC) with respect to the effect of the assigned study treatment on content/quantity of inflammatory cytokines and fibrinogen as well as bacteria. Higher mean wound area reduction was observed in the NLFU treatment group (67.0%) compared to the SOC group (41.6%, p < 0.05). Hypertension, diabetes type II, coronary artery disease, and anemia were identified as the most common comorbidities of the Chronic venous leg ulcer (CVLU) patients included in the study. Pseudomonas, Corynebacterium, and unclassified Enterobacteriaceae were dominant in the highest number of samples. Anaerococcus, Peptoniphilus, and Finegoldia, had the highest median proportion in the samples overall. Peptoniphilus abundance decreased more in the NLFU treatment group relative to SOC; similar trends were observed for Anaerococcus and Finegoldia. Progression of mediators like TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10 as well as PF4, TGF-beta, and fibrinogen was monitored and trends for several of the mediators were identified. Fibrinogen amounts were significantly reduced over time in the NLFU treatment group (p < 0.05). IL-8 levels declined in wound fluid from NLFU responders as well as SOC responders. Bacterial load (total bacterial abundance) determined local parameters of ulcer inflammation. If a bioburden of ≥ 10E was found compared to < 10E , levels of IL-1beta, IL-8, and TNF-alpha were significantly higher. In conclusion, NLFU treatment is an effective adjuvant tool for CVLU therapy. This study demonstrates that it improves wound healing by equally inhibiting abundant levels of pro-inflammatory cytokines as well as by reducing the overall bacterial burden.
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http://dx.doi.org/10.1111/wrr.12595DOI Listing
September 2017

Residual sodium dodecyl sulfate in decellularized muscle matrices leads to fibroblast activation in vitro and foreign body response in vivo.

J Tissue Eng Regen Med 2018 03 10;12(3):e1704-e1715. Epub 2017 Dec 10.

Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Detergents such as sodium dodecyl sulfate (SDS) are commonly used to extract cells from tissues in a process called "decellularization". Residual SDS is difficult to completely remove and may lead to an undesirable host response towards an implanted biomaterial. In this study, we developed a modification for SDS cell extraction from muscle equally efficient to previous methods but leading to significantly less residual SDS remnants in the matrices. Muscle-derived matrices were prepared via 2 SDS-based decellularization methods, which led to removal of either 81.4% or 98.4% of the SDS. In vitro, matrices were seeded with thp1 macrophages and primary human foreskin fibroblasts. By Day 2, both matrices demonstrated similar macrophage polarization; however, fibroblasts cultured on matrices with greater residual SDS expressed higher levels of mRNA associated with fibroblast activation: α-smooth muscle actin and connective tissue growth factor. In vivo, Collagen I gels spiked with increasing concentrations of SDS displayed a corresponding decrease in cell infiltration when implanted subcutaneously in rats after 4 days. Finally, as a model for muscle regeneration, matrices produced by each method were implanted in rat latissimus dorsi defects. At POD 30 greater levels of IL-1β mRNA were present in defects treated with matrices containing higher levels of SDS, indicating a more severe inflammatory response. Although matrices containing higher levels of residual SDS became encapsulated by POD 30 and showed evidence of a foreign body response, matrices with the lower levels of SDS integrated into the defect area with lower levels of inflammatory and fibrosis-related gene expression.
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http://dx.doi.org/10.1002/term.2604DOI Listing
March 2018

Baseline factors affecting closure of venous leg ulcers.

J Vasc Surg Venous Lymphat Disord 2017 11;5(6):829-835.e1

Smith & Nephew, Inc, Fort Worth, Tex; Department of Pediatrics, University of North Texas Health Science Center, Fort Worth, Tex.

Objective: The objective of this study was to characterize factors associated with closure of venous leg ulcers (VLUs) in a pooled analysis of subjects from three randomized clinical trials.

Methods: Closure of VLUs after treatment with HP802-247, an allogeneic living cell therapy consisting of growth-arrested human keratinocytes and fibroblasts, vs standard therapy with compression bandaging was evaluated in three phase 3 clinical trials of similar design. Two trials enrolled subjects with VLUs ranging from 2 cm to 12 cm in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm and ≤36 cm with a 16-week treatment period. The first trial went to completion but failed to demonstrate a benefit to therapy with HP802-247 compared with placebo, and because of this, the remaining trials were terminated before completion. On the basis of no differences in outcomes between groups, subjects from both HP802-247 and control groups were pooled across all three studies. Cox proportional hazards regression analysis was employed to evaluate factors associated with VLU closure.

Results: This analysis included data from 716 subjects with VLU. Factors evaluated for association with healing included age, gender, race, diabetes, glycated hemoglobin level, body mass index, treatment (HP802-247 vs compression alone), and ulcer characteristics including location and area and duration at baseline. In an initial model including all of these putative factors, the following were significant at the P < .10 level: diagnosis of diabetes mellitus, gender, wound location (ankle or leg), baseline wound area, and wound duration at baseline. In a final model including only these factors, all but diabetes mellitus were significant at the P < .05 level. Effect sizes were as follows (hazard ratio [95% confidence interval]): female gender (1.384 [1.134-1.690]), wound location on the leg (1.490 [1.187-1.871]), smaller wound area at baseline (0.907 [0.887-0.927]), and shorter wound duration at baseline (0.971 [0.955-0.987]).

Conclusions: Factors associated with VLU lesions including location, area, and duration were important predictors of healing. Women were more likely than men to achieve wound closure. Factors including body mass index, the presence of diabetes mellitus, and higher concentrations of glycated hemoglobin were not significant independent predictors of wound closure in this analysis.
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http://dx.doi.org/10.1016/j.jvsv.2017.06.017DOI Listing
November 2017

Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model.

Plast Reconstr Surg Glob Open 2017 Jun 14;5(6):e1294. Epub 2017 Jun 14.

Laboratory for Tissue Repair and Regenerative Surgery, Division of Plastic and Reconstructive Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill.

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 White rabbits were divided into 2 study groups, with 6 rabbits receiving 10 μm pravastatin intradermally at postoperative days 15, 18, and 21, and 14 rabbits receiving 0.4%, 2%, and 10% simvastatin topical application at postoperative days 14-25. Four or 6 full-thickness circular dermal punches 7 mm in diameter were made on the ventral surface of the ear down to but not including the perichondrium. Specimens were collected at 28 days to evaluate the effects of statins on hypertrophic scarring.

Results: Treatment with pravastatin intradermal administration significantly reduced scarring in terms of scar elevation index. Topical treatment with both medium- and high-dose simvastatin also significantly reduced scarring. High-dose simvastatin topical treatment showed a major effect in scar reduction but induced side effects of scaling, erythema, and epidermal hyperplasia, which were improved with coapplication of cholesterol. There is a dose response in scar reduction with low-, medium- and high-dose simvastatin topical treatment. High-dose simvastatin treatment significantly reduced the messenger ribonucleic acid (mRNA) expression of connective tissue growth factor, consistent with our previously published work on intradermally injected statins. More directly, high-dose simvastatin treatment also significantly reduced the mRNA expression of collagen 1A1.

Conclusions: Topical simvastatin significantly reduces scar formation. The mechanism of efficacy for statin treatment through interference with connective tissue growth factor mRNA expression was confirmed.
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http://dx.doi.org/10.1097/GOX.0000000000001294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505822PMC
June 2017

Topical application of Dermatophagoides farinae or oxazolone induces symptoms of atopic dermatitis in the rabbit ear.

Arch Dermatol Res 2017 Sep 30;309(7):567-578. Epub 2017 Jun 30.

Laboratory for Tissue Repair and Regenerative Surgery, Plastic Surgery Division, Department of Surgery, Northwestern University, Feinberg School of Medicine, 745 Fairbanks Ct, Chicago, IL, 60611, USA.

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 of AD. In this study, we established two AD models in rabbits by applying an allergen, Dermatophagoides farinae (Der f), or a hapten, oxazolone (OXZ). Application of the allergen or hapten induced a rapid onset and a chronically sustained AD-like skin lesion. The clinical symptoms, which include skin erythema, scaling, papula and edema, of AD-like rabbit skin were similar to those in human AD. Histological analysis showed that allergen- or hapten-treated rabbit skin showed increased epidermal thickening and inflammatory cell infiltration. Furthermore, PCNA and keratin 10 (K10) staining revealed excessive proliferation and insufficient differentiation of the epidermis in the rabbit AD-like skin. Western blot analysis showed decreased expression of thymic stromal lymphopoietin (TSLP), an AD cytokine, in the rabbit AD-like skin. Our results suggest that the allergen- or hapten-induced rabbit AD models have pathological features of human AD-like symptoms and will be useful for evaluating both pathogenic mechanisms and potential therapeutic agents for human AD.
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http://dx.doi.org/10.1007/s00403-017-1758-8DOI Listing
September 2017

Adipose Tissue Drives Response to Ischemia-Reperfusion Injury in a Murine Pressure Sore Model.

Plast Reconstr Surg 2017 May;139(5):1128e-1138e

Chicago, Ill.

Background: Ischemia-reperfusion injury contributes significantly to the pathogenesis of chronic wounds such as pressure sores and diabetic foot ulcers. The authors' laboratory has previously developed a cyclical murine ischemia-reperfusion injury model. The authors here use this model to determine factors underlying tissue response to ischemia-reperfusion injury.

Methods: C57BL/6 mice were subjected to cycles of ischemia-reperfusion that varied in number (one to four cycles) and duration of ischemia (1 to 2 hours). For each ischemia-reperfusion condition, the following variables were analyzed: (1) digital photographs for area of necrosis; (2) hematoxylin and eosin staining and immunohistochemistry for inflammatory infiltrate; and (3) expression of inflammatory markers by quantitative polymerase chain reaction. In addition, human adipocytes and fibroblasts were cultured in vitro under conditions of hypoxia and reoxygenation, and expression of inflammatory markers was analyzed by quantitative polymerase chain reaction.

Results: Increases in both ischemia-reperfusion cycle number and ischemia duration correlated with increased areas of epithelial necrosis both grossly and histologically, and with an increase in cellularity and neutrophil density. This increased inflammatory infiltrate and a significant increase in the expression of proinflammatory markers (Hmox1, interleukin-6, interleukin-1, and monocyte chemoattractant protein-1) was observed in adipose tissue subjected to ischemia-reperfusion injury, but not in dermis. These results were mirrored in human adipose tissue.

Conclusions: The authors further characterize a novel, reproducible murine model of ischemia-reperfusion injury. The results of their study indicate that adipose tissue is less tolerant of ischemia-reperfusion than dermal tissue. Rather than being an "innocent bystander," adipose tissue plays an active role in driving the inflammatory response to ischemia-reperfusion injury.
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http://dx.doi.org/10.1097/PRS.0000000000003271DOI Listing
May 2017

Thermal injury model in the rabbit ear with quantifiable burn progression and hypertrophic scar.

Wound Repair Regen 2017 04 16;25(2):327-337. Epub 2017 May 16.

Division of Plastic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Hypertrophic scar is a major clinical outcome of deep-partial thickness to full thickness thermal burn injury. Appropriate animal models are a limitation to burn research due to the lack of, or access to, animal models which address the endpoint of hypertrophic scar. Lower species, such as rodents, heal mainly by contracture, which limits the duration of study. Higher species, such as pigs, heal more similarly to humans, but are associated with high cost, long duration for scar development, challenges in quantifying scar hypertrophy, and poor manageability. Here, we present a quantifiable deep-partial thickness burn model in the rabbit ear. Burns were created using a dry-heated brass rod for 10 and 20 seconds at 90 °C. At the time of eschar excision on day 3, excisional wounds were made on the contralateral ear for comparison. Burn wound progression, in which the wound size expands over time is a major distinction between excisional and thermal injuries, was quantified at 1 hour and 3 days after the injuries using calibrated photographs and histology and the size of the wounds was found to be unchanged from the initial wound size at 1 hour, but 10% in the 20 seconds burn wounds at 3 days. A quantifiable hypertrophic scar, measured by histology as the scar elevation index, was present in both 20 seconds burn wounds and excisional wounds at day 35. ImageJ measurements revealed that the 20 seconds burn wound scars were 22% larger than the excisional wound scars and the 20 seconds burn scar area measurements from histology were 26% greater than in the excisional wound scar. The ability to measure both burn progression and scar hypertrophy over a 35-day time frame suits this model to screening early intervention burn wound therapeutics or scar treatments in a burn-specific scar model.
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http://dx.doi.org/10.1111/wrr.12518DOI Listing
April 2017

Human Reticular Acellular Dermal Matrix in the Healing of Chronic Diabetic Foot Ulcerations that Failed Standard Conservative Treatment: A Retrospective Crossover Study.

Wounds 2017 Feb;29(2):39-45

Angiogenesis Foundation, Cambridge, MA.

Background: Acellular matrices have been successfully used to heal indolent diabetic foot ulcers (DFUs). These tissues include allogenic dermis as well as xenograft dermis, pericardium, and small intestine submucosa. While all of these tissues show promise for healing DFUs, dermal-derived matrices have shown considerable potential.

Materials And Methods: The authors retrospectively reviewed healing in patients with DFUs that failed the standard of care (SOC) treatment from a previous prospective randomized, controlled trial (RCT). That trial compared the efficacy of human reticular acellular dermal matrices (HR-ADMs) with the SOC. Of the 16 out of 20 patients who did not heal in the SOC group, 12 were eligible for crossover treatment with the HR-ADM. The authors studied the rate of complete healing in that specific cohort after 12 weeks of crossover treatment.

Results: Of the 12 patients who were eligible for the HR-ADM, 10 (83%) achieved complete wound healing, with a mean healing time of 21 days to closure. The corresponding wound area reduction was from 1.7 cm2 to 0.6 cm2. The mean product cost to closure was $800/patient.

Conclusion: This study further demonstrates the effectiveness of the HR-ADM in facilitating the closure of nonhealing DFUs refractory to SOC.
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February 2017

Donor-site Morbidity of Medial and Lateral Thigh-based Flaps: A Comparative Study.

Plast Reconstr Surg Glob Open 2016 Nov 8;4(11):e1012. Epub 2016 Nov 8.

Division of Plastic Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill.; and Department of Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, Md.

Background: Free and pedicled medial and lateral thigh-based flaps are common reconstructive procedures. However, there have been no comparative studies of morbidity between medial and lateral donor sites.

Methods: We conducted an Enterprise Data Warehouse-based review of all the senior authors' (R.D.G., G.A.D., and M.S.A.) thigh-based free and pedicled flaps. Patient demographic data, donor-site complications, drain duration, and number of postoperative visits were collected and compared. Complications were also compared between fasciocutaneous flaps and muscle or myocutaneous flaps, and skin grafted donor sites.

Results: We analyzed 352 flap donor sites, with 155 medial and 197 lateral. Two hundred seventeen (217) flaps were pedicled. Flap types included 127 gracilis, 27 rectus femoris, 134 anterolateral thigh, and 36 vastus lateralis-only flaps. There were no significant differences in complications between medial (17.4%) and lateral thigh (21.3%) donor sites, although lateral thigh flaps had a mean of 1 additional postoperative visit. Rates of wound dehiscence/healing issues were significantly higher in both gracilis myocutaneous flaps (25.9%) and flaps requiring a skin grafted donor site (31.2%). Postoperative therapeutic anticoagulation was the only significant risk factor for a donor-site complication. Flap complications resulted in increased drain duration and postoperative office visits.

Conclusions: Donor-site morbidity is similar in both lateral and medial thigh-based flaps. The inclusion of muscle in the flap from either donor site does not seem to increase complications, but the inclusion of a skin paddle with gracilis muscle, or a skin grafted lateral thigh donor site, results in increased wound healing complications.
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http://dx.doi.org/10.1097/GOX.0000000000001012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142470PMC
November 2016