Person:

Orgill, Dennis

Background: Wounds are increasingly important in our aging societies. Pathologies such as diabetes predispose patients to chronic wounds that can cause pain, infection, and amputation. The vacuum assisted closure device shows remarkable outcomes in wound healing. Its mechanism of action is unclear despite several hypotheses advanced. We previously hypothesized that micromechanical forces can heal wounds. To understand better the biological response of soft tissue to forces, rat ears in vivo were stretched and their gene expression patterns over time obtained. The absolute enrichment (AE) algorithm that obtains a combined up and down regulated picture of the expression analysis was implemented. Results: With the use of AE, the hypoxia gene set was the most important at a highly significant level. A co-expression network analysis showed that important co-regulated members of the hypoxia pathway include a glucose transporter (slc2a8), heme oxygenase, and nitric oxide synthase2 among others. Conclusion: It appears that the hypoxia pathway may be an important modulator of response of soft tissue to forces. This finding gives us insights not only into the underlying biology, but also into clinical interventions that could be designed to mimic within wounded tissue the effects of forces without all the negative effects that forces themselves create.

Background: While it is known that increasing surgeon experience is correlated with improved efficiency and safety in the reduction mammaplasty procedure, it is unclear whether these improvements lead to an erosion in patient satisfaction. Methods: The authors distributed the Breast-Q questionnaire to all patients who underwent bilateral reduction mammaplasty at their institution between 1995 and 2007. Univariate and multivariate analyses were performed to assess the relationship between postoperative patient satisfaction scores and surgeon experience, as well as to characterize those patients with particularly high or low satisfaction scores, in general. Results: A total of 279 (26.1%) completed surveys were analyzed. No statistically significant erosion in either Satisfaction with Breasts (SWB) or Satisfaction with Outcomes (SWO) scores were witnessed with increasing surgeon experience or efficiency. Patients older than 40 years demonstrated significantly higher SWB scores than younger patients (P = .004), while patients who suffered postoperative soft tissue necrosis demonstrated significantly lower SWB (P = .003) and SWO (P = .010) scores. Conclusions: Gains in operative efficiency with increasing surgeon experience do not appear to come at the expense of patient satisfaction in the reduction mammaplasty procedure. Younger patients and those who experience postoperative soft tissue necrosis appear to be at higher risk for reporting lower postoperative patient satisfaction scores.

Background: Acellular dermal matrices (ADMs) are frequently used in reconstructive surgery and as scaffolds to treat chronic wounds. The 3-dimensional architecture and extracellular matrix provide structural and signaling cues for repair and remodeling. However, most ADMs are not uniformly porous, which can lead to heterogeneous host engraftment. In this study, we hypothesized that a novel human reticular ADM (HR-ADM; AlloPatch Pliable, Musculoskeletal Transplant Foundation, Edison, N.J.) when aseptically processed would have a more open uniform structure with retention of biological components known to facilitate wound healing. Methods: The reticular and papillary layers were compared through histology and scanning electron microscopy. Biomechanical properties were assessed through tensile testing. The impact of aseptic processing was evaluated by comparing unprocessed with processed reticular grafts. In vitro cell culture on fibroblasts and endothelial cells were performed to showcase functional cell activities on HR-ADMs. Results: Aseptically processed HR-ADMs have an open, interconnected uniform scaffold with preserved collagens, elastin, glycosaminoglycans, and hyaluronic acid. HR-ADMs had significantly lower ultimate tensile strength and Young’s modulus versus the papillary layer, with a higher percentage elongation at break, providing graft flexibility. These preserved biological components facilitated fibroblast and endothelial cell attachment, cell infiltration, and new matrix synthesis (collagen IV, fibronectin, von Willebrand factor), which support granulation and angiogenic activities. Conclusions: The novel HR-ADMs provide an open, interconnected scaffold with native dermal mechanical and biological properties. Furthermore, aseptic processing retains key extracellular matrix elements in an organized framework and supports functional activities of fibroblasts and endothelial cells.

Background: Fat grafting is now widely used in plastic surgery. Long-term graft retention can be unpredictable. Fat grafts must obtain oxygen via diffusion until neovascularization occurs, so oxygen delivery may be the overarching variable in graft retention. Methods: We studied the peer-reviewed literature to determine which aspects of a fat graft and the microenvironment surrounding a fat graft affect oxygen delivery and created 3 models relating distinct variables to oxygen delivery and graft retention. Results: Our models confirm that thin microribbons of fat maximize oxygen transport when injected into a large, compliant, well-vascularized recipient site. The “Microribbon Model” predicts that, in a typical human, fat injections larger than 0.16 cm in radius will have a region of central necrosis. Our “Fluid Accommodation Model” predicts that once grafted tissues approach a critical interstitial fluid pressure of 9 mm Hg, any additional fluid will drastically increase interstitial fluid pressure and reduce capillary perfusion and oxygen delivery. Our “External Volume Expansion Effect Model” predicts the effect of vascular changes induced by preoperative external volume expansion that allow for greater volumes of fat to be successfully grafted. Conclusions: These models confirm that initial fat grafting survival is limited by oxygen diffusion. Preoperative expansion increases oxygen diffusion capacity allowing for additional graft retention. These models provide a scientific framework for testing the current fat grafting theories.

Introduction

The Cook-Swartz implantable Doppler monitors venous or arterial blood flow from free flaps and can detect free-flap compromise. Previous studies have shown that the use of this Doppler can improve detection and salvage rates as it provides an earlier warning than the current method of clinical assessment. Such studies assert that the implantable Doppler is of great value in monitoring free flaps in current microsurgical units. This systematic review aims to compare the efficacy of the Cook-Swartz implantable Doppler in monitoring free-flap compromise against conventional clinical free-flap monitoring techniques.

Methods and analysis

Various electronic databases will be systematically searched for studies that compare the use of Cook-Swartz implantable Doppler with clinical assessment. The selected studies will then have their titles and abstracts screened by two authors. Articles selected after title and abstract screen will have full text downloaded and the complete article will be assessed for suitability. Once the articles have been selected for inclusion, data extraction will take place. For data analysis, the outcomes of the studies will be tabulated, with descriptive statistics performed as appropriate and the detection rate of the Doppler and clinical assessment will be compared and synthesised where possible.

Ethics and dissemination

The authors hope to disseminate the findings as widely as possible. This systematic review will be published in a peer-reviewed journal and include a number of recommendations as its conclusion based on the evidence contained within. Given the wide range of specialties now utilising flaps, it will be presented at a wide range of national and international conferences.

Mast cells (MCs) are active participants in blood coagulation and innate and acquired immunity. This review focuses on the development of mouse and human MCs, as well as the involvement of their granule serine proteases in inflammation and the connective tissue remodeling that occurs during the different phases of the healing process of wounded skin and other organs. The accumulated data suggest that MCs, their tryptases, and their chymases play important roles in tissue repair. While MCs initially promote healing, they can be detrimental if they are chronically stimulated or if too many MCs become activated at the same time. The possibility that MCs and their granule serine proteases contribute to the formation of keloid and hypertrophic scars makes them potential targets for therapeutic intervention in the repair of damaged skin.

Introduction

There is growing interest in the potential use of autologous fat grafting (AFG) for the purposes of breast reconstruction. However, concerns have been raised regarding the technique's clinical effectiveness, safety and interference with screening mammography. The objective of this systematic review was to determine the oncological, clinical, aesthetic and functional, patient reported, process and radiological outcomes for AFG.

Methods and analysis

All original studies, including randomised controlled trials, cohorts studies, case–control studies, case series and case reports involving women undergoing breast reconstruction. All AFG techniques performed for the purposes of reconstruction in the postmastectomy or breast conserving surgery setting will be considered. Outcomes are defined within this protocol along; oncological, clinical, aesthetic and functional, patient reported, process and radiological domains. The search strategy has been devised to find papers about ‘fat grafting and breast reconstruction’ and is outlined within the body of this protocol. The full search strategy is outlined within the body of the protocol. The following electronic databases will be searched from 1 January 1986 to 6 June 2013: PubMed, MEDLINE, EMBASE, SCOPUS, CINAHL, PsycINFO, SciELO, The Cochrane Library, including the Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effect (DARE), the Cochrane Methodology Register, Health Technology Assessment Database, the NHS Economic Evaluation Databases and Cochrane Groups, ClinicalTrials.gov, Current Controlled Trials Database, the World Health Organisation (WHO) International Clinical Trials Registry Platform, UpToDate.com, NHS Evidence and the York Centre for Reviews and Dissemination. Grey literature searches will also be conducted as detailed in our review protocol. Eligibility assessment occurred in two stages, title and abstract screening and then full text assessment. Data were extracted and stored in a database with standardised extraction fields to facilitate easy and consistent data entry.

Ethics and dissemination

This systematic review will be published in a peer-reviewed journal. It will also be presented at national and international conferences in the fields of plastic, reconstructive and aesthetic surgery and at more general surgical and methodological conferences. It will be disseminated electronically and in print. Brief reports of the review findings will be disseminated directly to the appropriate audiences of surgeons and societies through email and other modes of communication. Updates of the review will be conducted to inform and guide healthcare practice and policy.

Protocol Registration

PROSPERO—National Institute of Health Research (NIHR) Prospective Register of Systematic Reviews (CRD42013005254)

Background: Mechanical stretch has been shown to induce vascular remodeling and increase vessel density, but the pathophysiologic mechanisms and the morphologic changes induced by tensile forces to dermal vessels are poorly understood.

Methods: A custom computer-controlled stretch device was designed and applied to the backs of C57BL/6 mice (n = 38). Dermal and vascular remodeling was studied over a 7-day period. Corrosion casting and three-dimensional scanning electron microscopy and CD31 staining were performed to analyze microvessel morphology. Hypoxia was assessed by immunohistochemistry. Western blot analysis of vascular endothelial growth factor (VEGF) and mRNA expression of VEGF receptors was performed.

Results: Skin stretching was associated with increased angiogenesis as demonstrated by CD31 staining and vessel corrosion casting where intervascular distance and vessel diameter were decreased (p < 0.01). Immediately after stretching, VEGF dimers were increased. Messenger RNA expression of VEGF receptor 1, VEGF receptor 2, neuropilin 1, and neuropilin 2 was increased starting as early as 2 hours after stretching. Highly proliferating epidermal cells induced epidermal hypoxia starting at day 3 (p < 0.01).

Conclusions: Identification of significant hypoxic cells occurred after identification of neovessels, suggesting an alternative mechanism. Increased expression of angiogenic receptors and stabilization of VEGF dimers may be involved in a mechanotransductive, prehypoxic induction of neovascularization.

Background: Vacuum-assisted closure induces microdeformations of the wound surface and accelerates healing of complex wounds; however, a thorough understanding of the biology of cellular mechanotransduction is lacking. We hypothesized that fibroblast shape and function can be altered in an in vitro vacuum-assisted closure device.

Methods: A 3-dimensional fibrin matrix with cultured murine fibroblasts and an intervening polyurethane foam was exposed to 125 mm Hg suction and compared with similar wells without suction. We measured fibroblast proliferation and morphology using fluorescence microscopy and gene expression change using real-time reverse-transcriptase polymerase chain reaction at 24, 48, and 72 hours.

Results: Wells exposed to suction induced significant proliferation of fibroblasts and morphologic changes visible by larger, rounder, and notable dendrite-like branching and process extensions. Type 1 collagen alpha 1 (COL1A1), fibroblast growth factor 2 (FGF2, bFGF), and transforming growth factor beta 1 (TGF[beta]1) were all up-regulated after 48 hours of exposure to suction. Smooth muscle actin alpha 2 (Acta2, [alpha]-SMA) was up-regulated after 72 hours.

Conclusions: Microdeformations produced by the combination of polyurethane foam and suction are associated with increased fibroblast proliferation and up-regulation of gene expressions in fibroblasts.