The use of dCELL (decellularized human dermis) for primary and revision hypospadias repair: A case-control study.

INTRODUCTION: A dartos interposition flap is often used as a waterproofing layer in hypospadias repairs. Recently, acellular dermal matrices (ADMs) have been described as an alternative. In this case-control study we compare the outcomes of using dCELL (an ADM) with dartos flap. METHODS: A retrospective, case-control study was conducted, comparing the use of dCELL in primary and revision cases to controls. Patients were matched according to age and surgical technique. Data were analysed using an independent t-test. RESULTS: 13 patients undergoing primary distal hypospadias repair using dCELL as an interposition layer were matched with 13 controls. There was no significant difference in the number of complications between the groups (p = 0.296). 5 patients undergoing revision surgery using dCELL were also matched in the same way. Although a statistically significant lower complication rate was shown in the dCELL group compared to controls (p = 0.029), this may represent a type II error due to the small sample size and heterogeneity. CONCLUSION: Using dCELL as an interposition layer was not associated with any reduction in complication rates for primary distal hypospadias repair and possibly useful in soft tissue-deficient reoperative cases. However, larger randomised controlled trials may be needed to confirm the presence (or absence) of any benefit from using dCELL in hypospadias surgery.

Microorganisms and Breast Cancer: An In-Depth Analysis of Clinical Studies.

Breast cancer is a multifactorial disease that affects millions of women worldwide. Recent work has shown intriguing connections between microorganisms and breast cancer, which might have implications for prevention and treatment. This article analyzed 117 relevant breast cancer clinical studies listed on ClinicalTrials.gov selected using a bespoke set of 38 search terms focused on bacteria, viruses, and fungi. This was supplemented with 20 studies found from a search of PubMed. The resulting 137 studies were described by their characteristics such as geographic distribution, interventions used, start date and status, etc. The studies were then collated into thematic groups for a descriptive analysis to identify knowledge gaps and emerging trends.

Priority setting in breast reconstructive surgery: A DELPHI consensus.

OBJECTIVES: Breast reconstructive surgery is often performed following breast cancer treatment to restore the natural appearance of the breast. Despite various research performed in this field, there is a discrepancy between the research question that is considered crucial jointly by patients, carers and healthcare professionals and the research performed. The Breast Reconstruction Priority Setting Partnership was formed to determine the top research priorities in all aspects of breast reconstructive surgery. METHODS: The Priority Setting Partnership (PSP) was conducted in line with James Lind Alliance (JLA) principles involving patients and clinicians. An online survey was conducted to gather uncertainties related to breast reconstruction by involving patients, carers and clinicians. Following this, a modified Delphi consensus process was performed to identify the top 10 research priorities. RESULT: A total of 239 unique research uncertainties were identified via the online survey, which involved 100 participants. A review of literature established that 58 of these uncertainties did not have a high-quality systematic review, prompting the need for more in-depth research. A further 28 research uncertainties were obtained by performing a literature search. Of the final 86 unique questions, the Delphi panel achieved consensus on the top ten research priorities. Recommendations to address these research priorities have been put forward based on current evidence. CONCLUSION: This study involved patients, carers and healthcare professionals to establish the top 10 priority areas for research in breast reconstructive surgery. Recommendations have been put forward on the necessary future research that is required to address these uncertainties.

Is the skin microbiota a modifiable risk factor for breast disease?: A systematic review.

PURPOSE: High prevalence, unreliable risk discrimination and poor clinical outcomes are observed in malignant and benign breast diseases (BD). The involvement of microbial communities in the development of BD has become topical, and distal influences of microbial dysregulation in the breast have been well established. Despite advances, the role of the breast skin microbiota in BD remains unclear. Interactions between the skin microbiota and the underlying mucosal immune system are complex. In homeostasis, the skin offers a physical barrier protecting underlying breast tissue from skin commensals and noxious environmental triggers. Our review aims to illuminate the role of the skin microbiota in the development of BD. METHODS: Adhering to the PRISMA protocol, a systematic review was conducted utilising the Medline and Embase search engines. RESULTS: Through a comprehensive search of the last ten years, twenty-two studies satisfied the inclusion criteria. Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes were identified as the most prevalent phyla of both breast tissue and skin in healthy controls and BD. High abundance of skin commensals, specifically some species of Staphylococcus, have been linked in breast cancer and metastases. Similarly, dysregulated microbial abundance is also seen in inflammatory and implant-associated BD. These findings raise the hypothesis that the skin microbiota plays a role in tissue homeostasis and may contribute to a range of breast pathologies. Several mechanisms of microbial transfer to underlying tissue have been proposed, including retrograde transfer through ductal systems, breakdown of the skin barrier, and migration through nipple-aspirate fluid. CONCLUSION: Our review provides preliminary insights into the skin microbiota as a modifiable risk factor for BD. This raises opportunities for future studies in antimicrobials/probiotics as an adjunct to, or replacement of surgery; a diagnostic and/or prognostic tool for BD; and the possibility of conditioning the microbiota to manage BD.

Use of dCELL (Decellularized Human Dermis) in Repair of Urethrocutaneous Fistulas or Glans Dehiscence.

BACKGROUND: In hypospadias repairs, there is some evidence to suggest that a "waterproofing" layer can be helpful in reducing the risk of urethrocutaneous fistula formation. The most likely role of this layer is to prevent the creation of overlapping suture lines. Many hypospadias surgeons use a dartos fascia interposition flap for this purpose. However, raising a dartos fascia flap adds time to the procedure, can result in devascularization of the overlying skin, and can create unsightly torsion of the penis, which may be hard to correct. To avoid these problems, the senior author has started to use dCELL (decellularized human dermis) as an alternative to dartos fascia to separate the suture lines. METHODS: Between March and July 2018, a pilot study was performed in 8 patients undergoing closure of a urethrocutaneous fistula or glans dehiscence combined with dCELL. Data on infections, wound breakdown, length of stay and catheterization, surgical time, and hospital stay were collected. RESULTS: All patients had a successful reconstruction. One patient developed a urinary tract infection, possibly related to prolonged catheterization following his repair. CONCLUSION: Our results suggest that dCELL may be useful in the repair of urethrocutaneous fistulas and glans dehiscence after hypospadias surgery.

Radiation-induced fibrosis in breast cancer: A protocol for an observational cross-sectional pilot study for personalised risk estimation and objective assessment.

INTRODUCTION: About 30% of patients request breast reconstruction following surgery for breast cancer, but radiation therapy negatively influences the outcome. Post-reconstruction radiotherapy is associated with more complications, including more severe capsular contracture and inferior cosmetic results. In general, less fibrosis is seen if autologous reconstruction is performed after radiotherapy, so surgeons will often delay reconstruction until after radiotherapy is complete. Drawbacks to this approach include additional surgery, recuperation, cost, and an extended reconstructive process. Randomised clinical trials are required to determine the best approach. METHODS AND ANALYSIS: The aim of this cross-sectional pilot study is to see if it is feasible to recruit women, and gather the required data. This information will be used to design a subsequent, larger study whose aim is to identify factors that increase the risk of radiation-induced fibrosis, and use these to develop a personalised risk-prediction tool, to enable the clinician and patient to have a more informed discussion when treatment for breast cancer is being discussed. Identification of the risk factors will also enable the development of methods to minimise the risk, which would have applications in other medical conditions where fibrosis is a problem. In addition, the project will develop objective methods of assessing fibrosis, and will determine the psychological and economic impacts that fibrosis has affected individuals. A better understanding of the long-term effects of radiotherapy on normal tissues such as the heart and lungs may also have applications in other medical conditions where fibrosis is a problem. ETHICS AND DISSEMINATION: The study has been submitted for ethical approval (REC reference). Findings will be made available to patients and clinicians through presentations at national and international meetings, peer-reviewed publications, social media and patient support groups. TRIAL REGISTRATION: Registered on ClinicalTrials.gov (after REC approval).

Evaluation of Sterilisation Techniques for Regenerative Medicine Scaffolds Fabricated with Polyurethane Nonbiodegradable and Bioabsorbable Nanocomposite Materials.

An effective sterilisation technique that maintains structure integrity, mechanical properties, and biocompatibility is essential for the translation of new biomaterials to the clinical setting. We aimed to establish an effective sterilisation technique for a biodegradable (POSS-PCL) and nonbiodegradable (POSS-PCU) nanocomposite scaffold that maintains stem cell biocompatibility. Scaffolds were sterilised using 70% ethanol, ultraviolet radiation, bleach, antibiotic/antimycotic, ethylene oxide, gamma irradiation, argon plasma, or autoclaving. Samples were immersed in tryptone soya broth and thioglycollate medium and inspected for signs of microbial growth. Scaffold surface and mechanical and molecular weight properties were investigated. AlamarBlue viability assay of adipose derived stem cells (ADSC) seeded on scaffolds was performed to investigate metabolic activity. Confocal imaging of rhodamine phalloidin and DAPI stained ADSCs was performed to evaluate morphology. Ethylene oxide, gamma irradiation, argon plasma, autoclaving, 70% ethanol, and bleach were effective in sterilising the scaffolds. Autoclaving, gamma irradiation, and ethylene oxide led to a significant change in the molecular weight distribution of POSS-PCL and gamma irradiation and ethylene oxide to that of POSS-PCU (p<0.05). UV, ethanol, gamma irradiation, and ethylene oxide caused significant changes in the mechanical properties of POSS-PCL (p<0.05). Argon was associated with significantly higher surface wettability and ADSC metabolic activity (p<0.05). In this study, argon plasma was an effective sterilisation technique for both nonbiodegradable and biodegradable nanocomposite scaffolds. Argon plasma should be further investigated as a potential sterilisation technique for medical devices.

Nanoparticles in wound healing; from hope to promise, from promise to routine.

Chronic non-healing wounds represent a growing problem due to their high morbidity and cost. Despite recent advances in wound healing, several systemic and local factors can disrupt the weighed physiologic healing process. This paper critically reviews and discusses the role of nanotechnology in promoting the wound healing process. Nanotechnology-based materials have physicochemical, optical and biological properties unique from their bulk equivalent. These nanoparticles can be incorporated into scaffolds to create nanocomposite smart materials, which promote wound healing through their antimicrobial, as well as selective anti- and pro-inflammatory, and pro-angiogenic properties. Owed to their high surface area, nanoparticles have also been used for drug delivery as well as gene delivery vectors. In addition, nanoparticles affect wound healing by influencing collagen deposition and realignment and provide approaches for skin regeneration and wound healing.

The regenerative role of adipose-derived stem cells (ADSC) in plastic and reconstructive surgery.

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in plastic and reconstructive surgery. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. Adult mesenchymal stem cells appear to be an ideal stem cell population for practical regenerative medicine. Among these cells, adipose-derived stem cells (ADSC) have the potential to differentiate the mesenchymal, ectodermal and endodermal lineages and are easy to harvest. Additionally, adipose tissue yields a high number of ADSC per volume of tissue. Based on this background knowledge, the purpose of this review is to summarise and describe the proliferation and differentiation capacities of ADSC together with current preclinical data regarding the use of ADSC as regenerative tools in plastic and reconstructive surgery.

Adipose regeneration and implications for breast reconstruction: update and the future.

The evolution of breast reconstruction and management of breast cancer has evolved significantly since the earliest descriptions in the Edwin Smith Papyrus (3,000 BC). The development of surgical and scientific expertise has changed the way that women are managed, and plastic surgeons are now able to offer a wide range of reconstructive options to suit individual needs. Beyond the gold standard autologous flap based reconstructions, regenerative therapies promise the elimination of donor site morbidity whilst providing equivalent aesthetic and functional outcomes. Future research aims to address questions regarding ideal cell source, optimisation of scaffold composition and interaction of de novo adipose tissue in the microenvironment of breast cancer.

Slow chlorine releasing compounds: A viable sterilisation method for bioabsorbable nanocomposite biomaterials.

OBJECTIVE: Selection of the appropriate sterilisation method for biodegradable materials has been a challenging task. Many conventional sterilisation methods are not suitable for the next generation of biomaterials, mainly due to their complex composition, based on nanomaterials, often incorporating bioactive moieties. In this study, we investigate sterilisation efficacy of slow chlorine releasing compound sodium dichloroisocyanurate dihydrate (SDIC) for polyhedral oligomeric silsesquioxane (POSS)-poly(caprolactone urea-urethane) (PCL) scaffolds in comparison with conventional sterilisation methods. METHODS: POSS-PCL scaffolds were subjected to 70% ethanol, UV, and SDIC sterilisation methods. Samples were immersed in tryptone soya broth (TSB) and thioglycollate medium (THY) and after seven days visually inspected for signs of microbial growth. Bulk and surface properties and molecular weight distribution profiles of the scaffolds after sterilization were investigated using FTIR analysis, surface hydrophilicity, scanning electron microscopy analysis, tensile strength testing, and gel-permeation chromatography (GPC). Adipose-derived stem cells (ADSC) were seeded on the scaffolds and AlamarBlue® viability assay was performed to investigate cell metabolic activity. Confocal imaging of rhodamine phalloidin and Dapi stained ADSC on scaffolds was used to demonstrate cell morphology. RESULTS: GPC results showed that autoclaving led to a significant decrease in the molecular weight of POSS-PCL, whereas ethanol caused visible deformation of the polymer 3D structure and UV radiation did not effectively sterilise the scaffolds. AlamarBlue® analysis showed metabolic activity close to that of tissue culture plastic for ethanol and SDIC. CONCLUSION: SDIC sterilisation can be safely applied to biodegradable scaffolds unsuitable for the more common sterilisation methods.

Carbon Nanostructures in Bone Tissue Engineering.

BACKGROUND: Recent advances in developing biocompatible materials for treating bone loss or defects have dramatically changed clinicians' reconstructive armory. Current clinically available reconstructive options have certain advantages, but also several drawbacks that prevent them from gaining universal acceptance. A wide range of synthetic and natural biomaterials is being used to develop tissue-engineered bone. Many of these materials are currently in the clinical trial stage. METHODS: A selective literature review was performed for carbon nanostructure composites in bone tissue engineering. RESULTS: Incorporation of carbon nanostructures significantly improves the mechanical properties of various biomaterials to mimic that of natural bone. Recently, carbon-modified biomaterials for bone tissue engineering have been extensively investigated to potentially revolutionize biomaterials for bone regeneration. CONCLUSION: This review summarizes the chemical and biophysical properties of carbon nanostructures and discusses their functionality in bone tissue regeneration.

Octa-ammonium POSS-conjugated single-walled carbon nanotubes as vehicles for targeted delivery of paclitaxel.

BACKGROUND: Carbon nanotubes (CNTs) have unique physical and chemical properties. Furthermore, novel properties can be developed by attachment or encapsulation of functional groups. These unique properties facilitate the use of CNTs in drug delivery. We developed a new nanomedicine consisting of a nanocarrier, cell-targeting molecule, and chemotherapeutic drug and assessed its efficacy in vitro. METHODS: The efficacy of a single-walled carbon nanotubes (SWCNTs)-based nanoconjugate system is assessed in the targeted delivery of paclitaxel (PTX) to cancer cells. SWCNTs were oxidized and reacted with octa-ammonium polyhedral oligomeric silsesquioxanes (octa-ammonium POSS) to render them biocompatible and water dispersable. The functionalized SWCNTs were loaded with PTX, a chemotherapeutic agent toxic to cancer cells, and Tn218 antibodies for cancer cell targeting. The nanohybrid composites were characterized with transmission electron microscopy (TEM), Fourier transform infrared (FTIR), and ultraviolet-visible-near-infrared (UV-Vis-NIR). Additionally, their cytotoxic effects on Colon cancer cell (HT-29) and Breast cancer cell (MCF-7) lines were assessed in vitro. RESULTS: TEM, FTIR, and UV-Vis-NIR studies confirmed side-wall functionalization of SWCNT with COOH-groups, PTX, POSS, and antibodies. Increased cell death was observed with PTX-POSS-SWCNT, PTX-POSS-Ab-SWCNT, and free PTX compared to functionalized-SWCNT (f-SWCNT), POSS-SWCNT, and cell-only controls at 48 and 72 h time intervals in both cell lines. At all time intervals, there was no significant cell death in the POSS-SWCNT samples compared to cell-only controls. CONCLUSION: The PTX-based nanocomposites were shown to be as cytotoxic as free PTX. This important finding indicates successful release of PTX from the nanocomposites and further reiterates the potential of SWCNTs to deliver drugs directly to targeted cells and tissues.

Adipogenic differentiation of adipose-derived stem cells in 3-dimensional spheroid cultures (microtissue): implications for the reconstructive surgeon.

BACKGROUND: Adipose-derived stem cells (ADSC) can be readily extracted from adipose tissue, expanded in vitro, and have the capacity to differentiate into multiple cell lineages. This makes this cell type of great interest to the field of regenerative medicine. This study focuses on the isolation and characterisation of ADSC and their differentiation into adipocytes in a 3D microtissue model. METHODS: Human ADSC were isolated from abdominal adipose tissue and characterised using multiparameter flow cytometry. ADSC were then expanded in culture and used to produce 3D scaffold-free micro-tissue. Adipogenic differentiation potential of micro-tissue constructs were subsequently characterised using Oil Red O staining. RESULTS: Flow cytometric analysis showed ADSC were uniformly positive for CD34, CD73, CD90, and CD105, and negative for CD19, CD14, and CD45. The cells were functionally induced into adipocytes in the presence of appropriate conditioned media. CONCLUSION: We have demonstrated that adipose-derived stem cells have the ability to form of microtissue and survive in vitro. We postulate that in the future this will result in an ADSC population which is injectable and can extend the delivery options of current stem cell-based therapies.

Carbon nanotubes in the diagnosis and treatment of malignant melanoma.

The potential role of carbon nanotubes (CNTs) in the diagnosis and treatment of malignant melanoma (MM) is still an emerging area of research. To date, there is strong evidence for the efficiency of CNTs in this therapeutic area, despite their unique physical, mechanical and biological properties. In this review, the application of CNTs in cancer diagnostics and treatment is reviewed, and consideration is given to the toxicity issues associated with their use.

The efficacy of medicinal leeches in plastic and reconstructive surgery: a systematic review of 277 reported clinical cases.

BACKGROUND: Although there are numerous case reports and small case series describing the experiences of leech therapy in various circumstances, there are relatively few large studies evaluating the effectiveness of leeching to relieve venous congestion. The therapeutic value of leeching is illustrated by these reports but the current literature lacks a cohesive summary of previous experiences. METHODS: An electronic search of PubMed, the Cochrane library and the Centre for Reviews and Dissemination between 1966 and 2009 was used to retrieve human studies published in the English language evaluating outcomes following leech therapy. The "success" and "failure" of leech therapy were the primary outcome measures and secondary outcomes included complications, number of leeches used, pharmacological adjuncts and blood transfusion requirements. RESULTS: In total, out of 461 articles, 394 articles met the exclusion criteria. The 67 included papers reported on 277 cases of leech use with an age range of 2-81 years and a male to female ratio of almost 2:1. The overall reported "success" rate following leech therapy was 77.98% (216/277). In terms of secondary outcome measures, 49.75% of cases (N = 101) required blood transfusions, 79.05% received antibiotics (N = 166) and 54.29% received concomitant anticoagulant therapy. The overall complication rate was 21.8%. CONCLUSION: In the absence of robust randomized controlled trials on which the evidence may be based, this synthesis of current best evidence guides clinicians during the process of consenting patients and using leeches in their practice.

Application of OctaAmmonium-POSS functionalized single walled carbon nanotubes for thermal treatment of cancer.

INTRODUCTION: Single walled carbon nanotubes (SWCNTs) have distinctive physical and chemical properties. Additionally, innovative properties can be established to match the clinical need by attachment of functional groups to the SWCNT. In this experiment SWCNT was functionalized with OctaAmmonium-POSS. Evidence suggests that functionalization of SWCNT with OctaAmmonium-POSS would augment the dispersion of SWCNT. We further postulate that functionalization of SWCNT with OctaAmmonium-POSS would enhance the temperature increase of SWCNT upon exposure to NIR laser irradiation. METHODS: Functionalization of SWCNT was conferred by refluxing with acid and OctaAmmonium-POSS. Fourier Transform Infrared (FTIR) test UV-visible spectroscopy and morphology analysis using Transmission Electron Microscopy (TEM) confirmed successful functionalization of SWCNT. NIR irradiation of samples was conducted using an 808 nm laser at 1 watt. Temperature changes were documented using a thermal camera. A HT-29 colorectal cancer cell line was used as a model for photothermal ablation. Cell viability test was performed using trypan blue and fluorescence activated cell sorting (FACS) technique. Graph plotting and statistical analysis was conducted using Graph Pad Prism. RESULTS: Following the functionalization process, TEM images showed a layer on the surface of the SWCNT. In the FTIR experiment, results illustrated the presence of the -COOH group on the functionalized SWCNTs. Upon further functionalization of SWCNT with OctaAmmonium-POSS, various peaks determined the formation of amide bond between the POSS molecule and functionalized SWCNT. The UV-visible spectra also determine the successful functionalization of the SWCNT following its treatment with acid and OctaAmmonium-POSS. Upon exposure to NIR, OctaAmmonium-POSS-SWCNT was the only treatment group that illustrated significantly higher temperature increase than the other treatment groups. Additionally cell death of NIR irradiated OctaAmmonium-POSS-SWCNT was statistically significant compared to other treatment groups. CONCLUSION: OctaAmmonium-POSS was used to render SWCNT biocompatible and water dispersible. Observation from this study determines that functionalization with OctaAmmonium-POSS show greater temperature increase compared to pristine SWCNTs upon its exposure NIR. This significant temperature increase is due to increasing the solubility of SWCNT following its functionalization with OctaAmmonium-POSS.

A new era of cancer treatment: carbon nanotubes as drug delivery tools.

Cancer is a generic term that encompasses a group of diseases characterized by an uncontrolled proliferation of cells. There are over 200 different types of cancer, each of which gains its nomenclature according to the type of tissue the cell originates in. Many patients who succumb to cancer do not die as a result of the primary tumor, but because of the systemic effects of metastases on other regions away from the original site. One of the aims of cancer therapy is to prevent the metastatic process as early as possible. There are currently many therapies in clinical use, and recent advances in biotechnology lend credence to the potential of nanotechnology in the fight against cancer. Nanomaterials such as carbon nanotubes (CNTs), quantum dots, and dendrimers have unique properties that can be exploited for diagnostic purposes, thermal ablation, and drug delivery in cancer. CNTs are tubular materials with nanometer-sized diameters and axial symmetry, giving them unique properties that can be exploited in the diagnosis and treatment of cancer. In addition, CNTs have the potential to deliver drugs directly to targeted cells and tissues. Alongside the rapid advances in the development of nanotechnology-based materials, elucidating the toxicity of nanoparticles is also imperative. Hence, in this review, we seek to explore the biomedical applications of CNTs, with particular emphasis on their use as therapeutic platforms in oncology.

Medicinal leeches and the microsurgeon: a four-year study, clinical series and risk benefit review.

BACKGROUND: There are case reports and small series in the literature relating to the use of medicinal leeches by plastic surgeons; however, larger series from individual units are rare. The aim of this article is to present a comprehensive 4-year case series of the use of medicinal leeches, discuss the current evidence regarding indications, risks, and benefits and highlight the recent updates regarding leech speciation. METHODS: Patients prescribed leeches in a 4-year period (July 2004-2008) were collated from hospital pharmacy records (N = 35). The number of leeches used, demographic, clinical, and microbiological details were retrospectively analyzed. RESULTS: Thirty-five patients were treated with leeches. The age range was 2 to 98 years (mean = 49.3). Leeches were most commonly used for venous congestion in pedicled flaps and replantations. Blood transfusions were necessary in 12 cases (34%) [mean = 2.8 units, range 2-5 units]. Our infection rate was 20% (7/35) including five infections with Aeromonas spp. (14.2%). The proportion of patients becoming infected after leech therapy was significantly greater in the group of patients that did not receive prophylactic antibiotic treatment (Fisher's Exact test P = 0.0005). In total, 14 cases (40%) were salvaged in entirety, in 7 cases 80% or more, in 2 cases 50 to 79%, and in 1 case less than 50% of the tissues were salvaged. In 11 cases (31%), the tissues were totally lost. CONCLUSION: Our study highlights both the benefits and the risks to patients in selected clinical situations and also the potential risks. The routine use of antibiotic prophylaxis is supported. In view of the emerging evidence that Hirudo verbana are now used as standard leech therapy, and the primary pathogen is Aeromonas veronii, until a large prospective multicenter study is published, large series of patients treated with leeches should be reported.