Deferoxamine topical cream superior to patch in rescuing radiation-induced fibrosis of unwounded and wounded skin.

Topical patch delivery of deferoxamine (DFO) has been studied as a treatment for this fibrotic transformation in irradiated tissue. Efficacy of a novel cream formulation of DFO was studied as a RIF therapeutic in unwounded and excisionally wounded irradiated skin. C57BL/6J mice underwent 30 Gy of radiation to the dorsum followed by 4 weeks of recovery. In a first experiment, mice were separated into six conditions: DFO 50 mg cream (D50), DFO 100 mg cream (D100), soluble DFO injections (DI), DFO 1 mg patch (DP), control cream (Vehicle), and irradiated untreated skin (IR). In a second experiment, excisional wounds were created on the irradiated dorsum of mice and then divided into four treatment groups: DFO 100 mg Cream (W-D100), DFO 1 mg patch (W-DP), control cream (W-Vehicle), and irradiated untreated wounds (W-IR). Laser Doppler perfusion scans, biomechanical testing, and histological analysis were performed. In irradiated skin, D100 improved perfusion compared to D50 or DP. Both D100 and DP enhanced dermal characteristics, including thickness, collagen density and 8-isoprostane staining compared to untreated irradiated skin. D100 outperformed DP in CD31 staining, indicating higher vascular density. Extracellular matrix features of D100 and DP resembled normal skin more closely than DI or control. In radiated excisional wounds, D100 facilitated faster wound healing and increased perfusion compared to DP. The 100 mg DFO cream formulation rescued RIF of unwounded irradiated skin and improved excisional wound healing in murine skin relative to patch delivery of DFO.

Pharmacological and cell-based treatments to increase local skin flap viability in animal models.

Local skin flaps are frequently employed for wound closure to address surgical, traumatic, congenital, or oncologic defects. (1) Despite their clinical utility, skin flaps may fail due to inadequate perfusion, ischemia/reperfusion injury (IRI), excessive cell death, and associated inflammatory response. (2) All of these factors contribute to skin flap necrosis in 10-15% of cases and represent a significant surgical challenge. (3, 4) Once flap necrosis occurs, it may require additional surgeries to remove the entire flap or repair the damage and secondary treatments for infection and disfiguration, which can be costly and painful. (5) In addition to employing appropriate surgical techniques and identifying healthy, well-vascularized tissue to mitigate the occurrence of these complications, there is growing interest in exploring cell-based and pharmacologic augmentation options. (6) These agents typically focus on preventing thrombosis and increasing vasodilation and angiogenesis while reducing inflammation and oxidative stress. Agents that modulate cell death pathways such as apoptosis and autophagy have also been investigated. (7) Implementation of drugs and cell lines with potentially beneficial properties have been proposed through various delivery techniques including systemic treatment, direct wound bed or flap injection, and topical application. This review summarizes pharmacologic- and cell-based interventions to augment skin flap viability in animal models, and discusses both translatability challenges facing these therapies and future directions in the field of skin flap augmentation.

Observed face mask use outside retail chain stores during the COVID-19 pandemic in two cities in the state of Idaho, USA.

During the COVID-19 pandemic, public health authorities have encouraged the use of face masks to minimize transmission within the community. To assess mask wear during a COVID-19 surge and guide public health response efforts, including public messaging on mask recommendations, we compared observed mask use in the largest city in each of Idaho's 2 most populous counties, both without a current mask mandate. We recorded mask usage by every third person exiting stores of 5 retail chains in Boise and Nampa during November 8-December 5, 2021. Observations were conducted during three time periods (morning, afternoon, and evening) on weekday and weekend days. A multivariable model with city, retail chain, and city-chain interaction was used to assess mask wear differences by city for each chain. Of 3021 observed persons, 22.0% wore masks. In Boise, 31.3% (430/1376) of observed persons wore masks; in Nampa, 14.3% (236/1645) wore masks. Among all persons wearing masks, > 94% wore masks correctly; cloth and surgical masks were most common. By retail chain, observed individuals at Boise locations were 2.3-5.7 times as likely to wear masks than persons at respective Nampa locations. This study provided a rapid, nonconfrontational assessment of public use of mitigation measures in 2 Idaho cities during a COVID-19 surge.

A Review of Radiation-Induced Vascular Injury and Clinical Impact.

ABSTRACT: The number of cancer survivors continues to increase because of advances in therapeutic modalities. Along with surgery and chemotherapy, radiotherapy is a commonly used treatment modality in roughly half of all cancer patients. It is particularly helpful in the oncologic treatment of patients with breast, head and neck, and prostate malignancies. Unfortunately, among patients receiving radiation therapy, long-term sequalae are often unavoidable, and there is accumulating clinical evidence suggesting significant radiation-related damage to the vascular endothelium. Ionizing radiation has been known to cause obliterative fibrosis and increased wall thickness in irradiated blood vessels. Clinically, these vascular changes induced by ionizing radiation can pose unique surgical challenges when operating in radiated fields. Here, we review the relevant literature on radiation-induced vascular damage focusing on mechanisms and signaling pathways involved and highlight microsurgical anastomotic outcomes after radiotherapy. In addition, we briefly comment on potential therapeutic strategies, which may have the ability to mitigate radiation injury to the vascular endothelium.

Natural Compounds and Biomimetic Engineering to Influence Fibroblast Behavior in Wound Healing.

Throughout history, natural products have played a significant role in wound healing. Fibroblasts, acting as primary cellular mediators in skin wound healing, exhibit behavioral responses to natural compounds that can enhance the wound healing process. Identifying bioactive natural compounds and understanding their impact on fibroblast behavior offers crucial translational opportunities in the realm of wound healing. Modern scientific techniques have enabled a detailed understanding of how naturally derived compounds modulate wound healing by influencing fibroblast behavior. Specific compounds known for their wound healing properties have been identified. Engineered biomimetic compounds replicating the natural wound microenvironment are designed to facilitate normal healing. Advanced delivery methods operating at micro- and nano-scales have been developed to effectively deliver these novel compounds through the stratum corneum. This review provides a comprehensive summary of the efficacy of natural compounds in influencing fibroblast behavior for promoting wound regeneration and repair. Additionally, it explores biomimetic engineering, where researchers draw inspiration from nature to create materials and devices mimicking physiological cues crucial for effective wound healing. The review concludes by describing novel delivery mechanisms aimed at enhancing the bioavailability of natural compounds. Innovative future strategies involve exploring fibroblast-influencing pathways, responsive biomaterials, smart dressings with real-time monitoring, and applications of stem cells. However, translating these findings to clinical settings faces challenges such as the limited validation of biomaterials in large animal models and logistical obstacles in industrial production. The integration of ancient remedies with modern approaches holds promise for achieving effective and scar-free wound healing.

Topical vanadate improves tensile strength and alters collagen organisation of excisional wounds in a mouse model.

Wound dehiscence, oftentimes a result of the poor tensile strength of early healing wounds, is a significant threat to the post-operative patient, potentially causing life-threatening complications. Vanadate, a protein tyrosine phosphatase inhibitor, has been shown to alter the organisation of deposited collagen in healing wounds and significantly improve the tensile strength of incisional wounds in rats. In this study, we sought to explore the effects of locally administered vanadate on tensile strength and collagen organisation in both the early and remodelling phases of excisional wound healing in a murine model. Wild-type mice underwent stented excisional wounding on their dorsal skin and were divided equally into three treatment conditions: vanadate injection, saline injection control and an untreated control. Tensile strength testing, in vivo suction Cutometer analysis, gross wound measurements and histologic analysis were performed during healing, immediately upon wound closure, and after 4 weeks of remodelling. We found that vanadate treatment significantly increased the tensile strength of wounds and their stiffness relative to control wounds, both immediately upon healing and into the remodelling phase. Histologic analysis revealed that these biomechanical changes were likely the result of increased collagen deposition and an altered collagen organisation composed of thicker and distinctly organised collagen bundles. Given the risk that dehiscence poses to all operative patients, vanadate presents an interesting therapeutic avenue to improve the strength of post-operative wounds and unstable chronic wounds to reduce the risk of dehiscence.

Understanding the Role of Adipocytes and Fibroblasts in Cancer.

ABSTRACT: Cancer is currently the second leading cause of death in the United States. There is increasing evidence that the tumor microenvironment (TME) is pivotal for tumorigenesis and metastasis. Recently, adipocytes and cancer-associated fibroblasts (CAFs) in the TME have been shown to play a major role in tumorigenesis of different cancers, specifically melanoma. Animal studies have shown that CAFs and adipocytes within the TME help tumors evade the immune system, for example, by releasing chemokines to blunt the effectiveness of the host defense. Although studies have identified that adipocytes and CAFs play a role in tumorigenesis, adipocyte transition to fibroblast within the TME is fairly unknown. This review intends to elucidate the potential that adipocytes may have to transition to fibroblasts and, as part of the TME, a critical role that CAFs may play in affecting the growth and invasion of tumor cells. Future studies that illuminate the function of adipocytes and CAFs in the TME may pave way for new antitumor therapies.

Technical Tips to Reduce Implant Rippling in Staged Pre-pectoral Breast Reconstruction.

INTRODUCTION: Pre-pectoral implant-based breast reconstruction (IBR) is becoming increasingly popular, permitting optimal implant positioning on the chest wall, prevention of animation deformity, and reduced patient discomfort. There are, however, concerns related to increased rates of breast implant rippling in pre-pectoral (versus submuscular) IBR, which can prompt a patient to seek revisionary surgery. The aim of this study is to identify factors that can be implemented to reduce implant rippling in the setting of pre-pectoral IBR. METHODS: A literature review was conducted using the PubMed database to determine the rate of rippling in pre-pectoral IBR. Clinical studies in English were included. Further review was then performed to explore technical strategies associated with reduced rates of rippling in pre-pectoral two-stage breast reconstruction. RESULTS: Implant rippling has been reported with a rate varying from 0 to 53.8% in 25 studies of pre-pectoral IBR (including both direct-to-implant and two-stage IBR). The majority of studies reviewed did not demonstrate a significant association between BMI and rippling, suggesting that other factors, likely technical and device-related, contribute to the manifestation of implant rippling. Hence, we explored whether specific technical modifications could be implemented that would reduce the risk of rippling in patients undergoing pre-pectoral IBR. Specifically, we highlight the need for close attention to expansion protocol and pocket dimension, expander fill medium and implant characteristics, and the rationale behind adjunctive procedures to reduce implant rippling. CONCLUSION: Surgical modifications may reduce the incidence of rippling in pre-pectoral breast reconstruction. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The role of Wnt signaling in skin fibrosis.

Skin fibrosis is the excessive deposition of extracellular matrix in the dermis. Cutaneous fibrosis can occur following tissue injury, including burns, trauma, and surgery, resulting in scars that are disfiguring, limit movement and cause significant psychological distress for patients. Many molecular pathways have been implicated in the development of skin fibrosis, yet effective treatments to prevent or reverse scarring are unknown. The Wnt signaling pathways are known to play an important role in skin homeostasis, skin injury, and in the development of fibrotic skin diseases. This review provides a detailed overview of the role of the canonical Wnt signaling pathways in regulating skin scarring. We also discuss how Wnt signaling interacts with other known fibrotic molecular pathways to cause skin fibrosis. We further provide a summary of the different Wnt inhibitor types available for treating skin scarring. Understanding the role of the Wnt pathway in cutaneous fibrosis will accelerate the development of effective Wnt modulators for the treatment of skin fibrosis.

Transdermal deferoxamine administration improves excisional wound healing in chronically irradiated murine skin.

BACKGROUND: Radiation-induced skin injury is a well-known risk factor for impaired wound healing. Over time, the deleterious effects of radiation on skin produce a fibrotic, hypovascular dermis poorly suited to wound healing. Despite increasing understanding of the underlying pathophysiology, therapeutic options remain elusive. Deferoxamine (DFO), an iron-chelating drug, has been shown in prior murine studies to ameliorate radiation-induced skin injury as well as improve wound healing outcomes in various pathologic conditions when administered transdermally. In this preclinical study, we evaluated the effects of deferoxamine on wound healing outcomes in chronically irradiated murine skin. METHODS: Wild-type mice received 30 Gy of irradiation to their dorsal skin and were left to develop chronic fibrosis. Stented excisional wounds were created on their dorsal skin. Wound healing outcomes were compared across 4 experimental conditions: DFO patch treatment, vehicle-only patch treatment, untreated irradiated wound, and untreated nonirradiated wounds. Gross closure rate, wound perfusion, scar elasticity, histology, and nitric oxide assays were compared across the conditions. RESULTS: Relative to vehicle and untreated irradiated wounds, DFO accelerated wound closure and reduced the frequency of healing failure in irradiated wounds. DFO augmented wound perfusion throughout healing and upregulated angiogenesis to levels observed in nonirradiated wounds. Histology revealed DFO increased wound thickness, collagen density, and improved collagen fiber organization to more closely resemble nonirradiated wounds, likely contributing to the observed improved scar elasticity. Lastly, DFO upregulated inducible nitric oxide synthase and increased nitric oxide production in early healing wounds. CONCLUSION: Deferoxamine treatment presents a potential therapeutic avenue through which to target impaired wound healing in patients following radiotherapy.

Multistate outbreak of Salmonella Mbandaka infections linked to sweetened puffed wheat cereal - United States, 2018.

In May of 2018, PulseNet, the national molecular subtyping network for enteric pathogens, detected a multistate cluster of illnesses caused by an uncommon molecular subtype of Salmonella serovar Mbandaka. A case was defined as an illness in a person infected with the outbreak strain of Salmonella Mbandaka with illness onset on or after 3 March 2018 and before 1 September 2018. One-hundred thirty-six cases from 36 states were identified; 35 hospitalisations and no deaths were reported. Ill people ranged in age from <1 year to 95 years (median: 57 years). When standardised questionnaires did not generate a strong hypothesis, opened-ended interviews were performed. Sixty-three of 84 (75%) ultimately reported consuming or possibly consuming a specific sweetened puffed wheat cereal in the week before illness onset. Environmental sampling performed at the cereal manufacturing facility yielded the outbreak strain. The outbreak strain was also isolated from open cereal samples from ill people's homes and from a sealed retail sample. Due to these findings, the brand owner of the product issued a voluntary recall of the cereal on 14 June 2018. Additional investigation of the manufacturing facility identified persistent environmental contamination with Salmonella Mbandaka that was closely genetically related to other isolates in the outbreak. This investigation highlights the ability of Salmonella to survive in low-moisture environments, and the potential for prolonged outbreaks linked to products with long shelf lives and large distribution areas.

Readability of Online Patient Information Relating to Cleft Palate Surgery.

OBJECTIVE: It is important for health care education materials to be easily understood by caretakers of children requiring craniofacial surgery. This study aimed to analyze the readability of Google search results as they pertain to "Cleft Palate Surgery" and "Palatoplasty." Additionally, the study included a search from several locations globally to identify possible geographic differences. DESIGN: Google searches of the terms "Cleft Palate Surgery" and "Palatoplasty" were performed. Additionally, searches of only "Cleft Palate Surgery" were run from several internet protocol addresses globally. MAIN OUTCOME MEASURES: Flesch-Kincaid Grade Level and Readability Ease, Gunning Fog Index, Simple Measure of Gobbledygook (SMOG) index, and Coleman-Liau Index. RESULTS: Search results for "Cleft Palate Surgery" were easier to read and comprehend compared to search results for "Palatoplasty." Mean Flesch-Kincaid Grade Level scores were 7.0 and 10.11, respectively (P = .0018). Mean Flesch-Kincaid Reading Ease scores were 61.29 and 40.71, respectively (P = .0003). Mean Gunning Fog Index scores were 8.370 and 10.34, respectively (P = .0458). Mean SMOG Index scores were 6.84 and 8.47, respectively (P = .0260). Mean Coleman-Liau Index scores were 12.95 and 15.33, respectively (P = .0281). No significant differences were found in any of the readability measures based on global location. CONCLUSIONS: Although some improvement can be made, craniofacial surgeons can be confident in the online information pertaining to cleft palate repair, regardless of where the search is performed from. The average readability of the top search results for "Cleft Palate Surgery" is around the seventh-grade reading level (US educational system) and compares favorably to other health care readability analyses.

Fat Grafts Augmented With Vitamin E Improve Volume Retention and Radiation-Induced Fibrosis.

BACKGROUND: Treatments for radiation-induced fibrosis range from vitamin E (VE) and pentoxifylline (PTX) systemically to deferoxamine and fat grafting locally. Regarding fat grafting, volume retention hinders its long-term functionality and is affected by 2 factors: inflammation and necrosis secondary to hypovascularity. OBJECTIVE: The authors aimed to simultaneously improve fat graft retention and radiation-induced fibrosis by integrating VE and PTX into fat grafts locally. METHODS: Forty adult CD-1 nude male mice, 6 weeks old, underwent scalp irradiation and recovered for 4 weeks to allow for development of fibrosis. Mice received 200 µL of donor human fat graft to the scalp. Mice were separated into 4 conditions: no grafting, fat graft without treatment, graft treated with PTX, and graft treated with VE. Fat graft volume retention was monitored in vivo with micro-computed tomography scans at weeks 0, 1, 2, 4, 6, and 8 after grafting. Histological and cytokine analysis of the scalp skin and fat grafts were performed. RESULTS: VE-treated grafts had significant improvement in dermal thickness and collagen density of overlying skin compared with all other groups. VE decreased 8-isoprostane and increased CD31+ staining compared with the other grafted groups. Cytokine analysis revealed decreased inflammatory and increased angiogenic markers in both the fat graft and overlying skin of the VE group. Fat graft volume retention was significantly improved in the VE group starting at 1 week post grafting. CONCLUSIONS: Radiation-induced fibrosis and fat graft volume retention are both simultaneously improved with local administration of VE.

A comparative analysis of deferoxamine treatment modalities for dermal radiation-induced fibrosis.

The iron chelator, deferoxamine (DFO), has been shown to potentially improve dermal radiation-induced fibrosis (RIF) in mice through increased angiogenesis and reduced oxidative damage. This preclinical study evaluated the efficacy of two DFO administration modalities, transdermal delivery and direct injection, as well as temporal treatment strategies in relation to radiation therapy to address collateral soft tissue fibrosis. The dorsum of CD-1 nude mice received 30 Gy radiation, and DFO (3 mg) was administered daily via patch or injection. Treatment regimens were prophylactic, during acute recovery, post-recovery, or continuously throughout the experiment (n = 5 per condition). Measures included ROS-detection, histology, biomechanics and vascularity changes. Compared with irradiated control skin, DFO treatment decreased oxidative damage, dermal thickness and collagen content, and increased skin elasticity and vascularity. Metrics of improvement in irradiated skin were most pronounced with continuous transdermal delivery of DFO. In summary, DFO administration reduces dermal fibrosis induced by radiation. Although both treatment modalities were efficacious, the transdermal delivery showed greater effect than injection for each temporal treatment strategy. Interestingly, the continuous patch group was more similar to normal skin than to irradiated control skin by most measures, highlighting a promising approach to address detrimental collateral soft tissue injury following radiation therapy.

Regenerative medicine for skeletal muscle loss: a review of current tissue engineering approaches.

Skeletal muscle is capable of regeneration following minor damage, more significant volumetric muscle loss (VML) however results in permanent functional impairment. Current multimodal treatment methodologies yield variable functional recovery, with reconstructive surgical approaches restricted by limited donor tissue and significant donor morbidity. Tissue-engineered skeletal muscle constructs promise the potential to revolutionise the treatment of VML through the regeneration of functional skeletal muscle. Herein, we review the current status of tissue engineering approaches to VML; firstly the design of biocompatible tissue scaffolds, including recent developments with electroconductive materials. Secondly, we review the progenitor cell populations used to seed scaffolds and their relative merits. Thirdly we review in vitro methods of scaffold functional maturation including the use of three-dimensional bioprinting and bioreactors. Finally, we discuss the technical, regulatory and ethical barriers to clinical translation of this technology. Despite significant advances in areas, such as electroactive scaffolds and three-dimensional bioprinting, along with several promising in vivo studies, there remain multiple technical hurdles before translation into clinically impactful therapies can be achieved. Novel strategies for graft vascularisation, and in vitro functional maturation will be of particular importance in order to develop tissue-engineered constructs capable of significant clinical impact.

The Adrenergic System in Plastic and Reconstructive Surgery: Physiology and Clinical Considerations.

ABSTRACT: The primary organ systems and tissues concerning plastic and reconstructive surgery include the integument, vasculature, subcutis, and peripheral nerves, because these may individually or collectively be injured requiring reconstruction, or indeed be used in reconstruction themselves through grafts, flaps, or anastomoses. Adrenergic receptors are present throughout these anatomic components on the vasculature, adipose, platelets, immune cells, keratinocytes, melanocytes, fibroblasts, peripheral nerves, and tendons. Herein, the influence of adrenergic signaling on the physiology of anatomic components related to plastic surgery is discussed, along with clinical considerations of this systems involvement in procedures, such as free flap reconstruction, skin grafting, fat grafting, and other areas relevant to plastic and reconstructive surgery. Current evidence as well as potential for further investigation is discussed.

Optimizing the decellularization process of an upper limb skeletal muscle; implications for muscle tissue engineering.

Upper limb muscle reconstruction is required following cancer resection, trauma, and congenital deformities. Current surgical reconstruction of the muscle involves local, regional and free flaps. However, muscle reconstruction is not always possible due to the size of the defect and functional donor site morbidity. These challenges could be addressed with the production of scaffolds composed of an extracellular matrix (ECM) derived from decellularized human skeletal muscle. This study aimed to find an optimal technique to decellularize a flexor digitorum superficialis muscle. The first two protocols were based on a detergent only (DOT) and a detergent-enzymatic protocol (DET). The third protocol avoided the use of detergents and proteolytic enzymes (NDNET). The decellularized scaffolds were characterized using qualitative techniques including histological and immunofluorescent staining and quantitative techniques assessing deoxyribonucleic acid (DNA), glycosaminoglycan (GAG), and collagen content. The DOT protocol consisting of 2% SDS for 4 hours was successful at decellularizing human FDS, as shown by DNA content assay and nuclei immunofluorescence staining. The DOT protocol maintained the microstructure of the scaffolds as shown by Masson's trichrome staining and collagen and GAG content. DET and NDNET protocols maintained the ECM, but were unsuccessful in removing all DNA content after two cycles of decellularization. Decellularization of skeletal muscle is a viable option for muscle reconstruction using a detergent only technique for upper limb defects. Further testing in vivo will assess the effectiveness of decellularized scaffolds for upper limb muscle skeletal tissue engineering.

Measuring Differential Volume Using the Subtraction Tool for Three-Dimensional Breast Volumetry: A Proof of Concept Study.

Background. Three-dimensional (3D) photography provides a promising means of breast volumetry. Sources of error using a single-captured surface to calculate breast volume include inaccurate designation of breast boundaries and prediction of the invisible chest wall generated by computer software. An alternative approach is to measure differential volume using subtraction of 2 captured surfaces. Objectives. To explore 3D breast volumetry using the subtraction of superimposed images to calculate differential volume. To assess optimal patient positioning for accurate volumetric assessment. Methods. Known volumes of breast enhancers simulated volumetric changes to the breast (n = 12). 3D photographs were taken (3dMDtorso) with the subject positioned upright at 90° and posteriorly inclined at 30°. Patient position, breathing, distance and camera calibration were standardised. Volumetric analysis was performed using 3dMDvultus software. Results. A statistically significant difference was found between actual volume and measured volumes with subjects positioned at 90° (P < .05). No statistical difference was found at 30° (P = .078), but subsequent Bland-Altman analysis showed evidence of proportional bias (P < .05). There was good correlation between measured and actual volumes in both positions (r = .77 and r = .85, respectively). Univariate analyses showed breast enhancer volumes of 195 mL and 295 mL to incur bias. The coefficient of variation was 5.76% for single observer analysis. Conclusion. Positioning the subject at a 30° posterior incline provides more accurate results from better exposure of the inferior breast. The subtraction tool is a novel method of measuring differential volume. Future studies should explore methodology for application into the clinical setting.

Fat Hypertrophy as a Complication of Fat Transfer for Hemifacial Atrophy.

Fat hypertrophy is a less commonly known complication of autologous fat transfer. We present a 32-year-old female with left hemifacial atrophy associated with systemic sclerosis, who was treated with 7 fat transfer procedures to correct the facial asymmetry. A total of 236.5 mL of fat was injected to the hemiface over a 4-year period to achieve good symmetry. A progressively enlarging, painless, soft mass over the left parotid region was noted at 3 months after the final fat transfer procedure. Magnetic resonance imaging showed a markedly enlarged bulk of subcutaneous fat over the left cheek with no evidence of necrosis, edema, or pathologic enhancement. Concurrent weight gain was noted secondary to additional nutritional input. The patient's aesthetic, symptomatic, and functional concerns led to the subsequent removal of 115 mL fat by liposuction.

Argon plasma modified nanocomposite polyurethane scaffolds provide an alternative strategy for cartilage tissue engineering.

BACKGROUND: Children born with a small or absent ear undergo surgical reconstruction to create a suitable replacement using rib cartilage. To overcome the donor site morbidity and long-term pain of harvesting rib cartilage, synthetic materials can be a useful alternative. Medpor, is the currently used synthetic polyethylene material to replace missing facial cartilage but unfortunately it has high levels of surgical complications including infection and extrusion, making it an unsuitable replacement. New materials for facial cartilage reconstruction are required to improve the outcomes of surgical reconstruction. This study has developed a new nanomaterial with argon surface modification for auricular cartilage replacement to overcome the complications with Medpor. RESULTS: Polyurethanes nanocomposites scaffolds (PU) were modified with argon plasma surface modification (Ar) and compared to Medpor in vitro and in vivo. Ar scaffolds allowed for greater protein adsorption than Medpor and PU after 48 h (p < 0.05). Cell viability and DNA assays demonstrated over 14-days greater human dermal fibroblast adhesion and cell growth on Ar than PU and Medpor nanocomposites scaffolds (p < 0.05). Gene expression using RT-qPCR of collagen-I, fibronectin, elastin, and laminin was upregulated on Ar scaffolds compared to Medpor and PU after 14-days (p < 0.05). Medpor, unmodified polyurethane and plasma modified polyurethane scaffolds were subcutaneously implanted in the dorsum of mice for 12 weeks to assess tissue integration and angiogenesis. Subcutaneous implantation of Ar scaffolds in mice dorsum, demonstrated significantly greater tissue integration by H&E and Massons trichrome staining, as well as angiogenesis by CD31 vessel immunohistochemistry staining over 12-weeks (p < 0.05). CONCLUSIONS: Argon modified polyurethane nanocomposite scaffolds support cell attachment and growth, tissue integration and angiogenesis and are a promising alternative for facial cartilage replacement. This study demonstrates polyurethane nanocomposite scaffolds with argon surface modification are a promising biomaterial for cartilage tissue engineering applications.