The Arteriovenous Loop: Engineering of Axially Vascularized Tissue

Background: Most of the current treatment options for large-scale tissue defects represent a serious burden for the patients, are often not satisfying, and can be associated with significant side effects. Although major achievements have already been made in the field of tissue engineering, the clinical translation in case of extensive tissue defects is only in its early stages. The main challenge and reason for the failure of most tissue engineering approaches is the missing vascularization within large-scale transplants. Summary: The arteriovenous (AV) loop model is an in vivo tissue engineering strategy for generating axially vascularized tissues using the own body as a bioreactor. A superficial artery and vein are anastomosed to create an AV loop. This AV loop is placed into an implantation chamber for prevascularization of the chamber inside, e.g., a scaffold, cells, and growth factors. Subsequently, the generated tissue can be transplanted with its vascular axis into the defect site and anastomosed to the local vasculature. Since the blood supply of the growing tissue is based on the AV loop, it will be immediately perfused with blood in the recipient site leading to optimal healing conditions even in the case of poorly vascularized defects. Using this tissue engineering approach, a multitude of different axially vascularized tissues could be generated, such as bone, skeletal or heart muscle, or lymphatic tissues. Upscaling from the small animal AV loop model into a preclinical large animal model could pave the way for the first successful attempt in clinical application. Key Messages: The AV loop model is a powerful tool for the generation of different axially vascularized replacement tissues. Due to minimal donor site morbidity and the possibility to generate patient-specific tissues variable in type and size, this in vivo tissue engineering approach can be considered as a promising alternative therapy to current treatment options of large-scale defects

Unusual explosive growth of a squamous cell carcinoma of the scalp after electrical burn injury and subsequent coverage by sequential free flap vascular connection – a case report

BACKGROUND: Squamous cell carcinomos may arise from chronic ulcerating wounds in scars, most commonly postburn scars. Tumour growth usually takes place over months to years. Localization on the scalp is a relatively rare condition. CASE PRESENTATION: This report presents the case of a 63-year-old man with chronic ulceration of a postburn scar of the scalp due to an electrical burn 58 years ago. Sudden tumour growth started within weeks and on presentation already had extended through the skull into frontal cortex. After radical tumour resection, defect was covered with a free radial forearm flap. Local recurrence occurred 6 weeks later. Subsequent wide excision including discard of the flap and preservation of the radial vessels was followed by transfer of a free latissimus dorsi muscle flap, using the radial vessels of the first flap as recipient vessels. The patient received radiotherapy post-operatively. There were no problems with flap survivals or wound healing. Due to rapidly growing recurrence the patient died 2 months later. CONCLUSION: Explosive SCC tumour growth might occur in post-burn scars after more than 50 years. As a treatment option the use of sequential free flap connections might serve in repeated extensive tumour resections, especially in the scalp region, where suitable donor vessels are often located in distance to the defect

The History of Carbon Monoxide Intoxication

Intoxication with carbon monoxide in organisms needing oxygen has probably existed on Earth as long as fire and its smoke. What was observed in antiquity and the Middle Ages, and usually ended fatally, was first successfully treated in the last century. Since then, diagnostics and treatments have undergone exciting developments, in particular specific treatments such as hyperbaric oxygen therapy. In this review, different historic aspects of the etiology, diagnosis and treatment of carbon monoxide intoxication are described and discussed

Cannabidiol restores differentiation capacity of LPS exposed adipose tissue mesenchymal stromal cells

Multipotent mesenchymal stromal cells (MSCs) support wound healing processes. These cells express toll-like receptors (TLRs). TLRs perform important key functions when the immune system is confronted with danger signals. TLR ligation by lipopolysaccharides (LPS) activates MSCs and induces intracellular signaling cascades, which affect their differentiation profile, increase the release of inflammatory cytokines and the production of reactive oxygen species. Continuing exposure to LPS triggers prolonged inflammatory reactions, which may lead to deleterious conditions, e.g. non-healing wounds. Cannabidiol (CBD) exerts anti-inflammatory processes through cannabinoid receptor dependent and independent mechanisms. In the present study, we examined whether CBD could influence the inflammatory MSC phenotype. Exposure to LPS increased the release of IL-6, as well as other soluble factors, and elevated levels of oxidized macromolecules found in cell homogenisates. While the amount of IL-6 was unaffected, co-treatment with CBD reduced the oxidative stress acting on the cells. LPS inhibited adipogenic as well as chondrogenic differentiation, which was attenuated by CBD treatment. In the case of adipogenesis, the disinhibitory effect probably depended on CBD interaction with the peroxisome proliferator-activated receptor-γ. CBD could exert mild immunosuppressive properties on MSCs, while it most effectively acted anti-oxidatively and by restoring the differentiation capacity upon LPS treatment

Adipose-derived stem cells in cutaneous wound repair

Growing interest in regenerative medicine and advances in adipose tissue research have led to the identification of mesenchymal stem cells in adipose tissue, so called adipose tissue-derived stem cells (ASCs). Due to the simple and safe harvest technique as well as high regenerative capacity, ASCs are regarded as a potential source for various indications including cutaneous wound repair. This review provides a short overview over mechanisms of ASC action in cutaneous wound repair and data regarding its clinical application. Mostly experimental data provide accruing evidence for the supportive effect of ASCs in cutaneous wound healing by secretion of soluble factors, differentiation into keratinocyte and fibroblasts, neovascularization and interaction with myofibroblasts. A number of in vivo experiments also support a positive effect of ASCs in different wound healing models. Furthermore, first clinical data evaluated the feasibility of ASCs in the treatment of different wound healing pathologies, e.g., chronic ulcers and burn wounds. Although the majority of currently available data indicate a beneficial role of ASCs in cutaneous wound repair, additional detailed experimental studies and larger, high-quality clinical trials are required to provide a reliable statement on the true value of ASCs in this context