Reconstruction of Soft-Tissue Defects at the Foot and Ankle after Oncological Resection

Introduction: Solid malignancies at the foot and ankle region are rare and include mainly soft tissue sarcomas, bone sarcomas and skin malignancies. Complete surgical resection with clear margins still remains the mainstay of therapy in these malignancies. However, attainment of negative surgical margins in patients with locally advanced tumors of the foot and ankle region may require extensive surgery and could result in loss of extremity function. In these circumstances, plastic surgical techniques can frequently reduce functional impairment and cover soft tissue defects, particularly in cases of large tumor size or localization adjacent to critical anatomic structures, thereby improving the quality of life for these patients. The aim of this article is to illustrate the various treatment options of plastic surgery in the multimodal therapy of patients with malignant tumors of the foot and ankle region.Material und methods: This article is based on the review of the current literature and the evaluation of the author’s own patient database.Results: The local treatment of malignant extremity tumors has undergone major changes over the last few decades. Primary amputations have been increasingly replaced by limb-sparing techniques, preserving extremity function as much as possible. Although defect coverage at the foot and ankle region is demanding due to complex anatomical features and functional requirements, several plastic surgical treatment options can be implemented in the curative treatment of patients with malignant solid tumors in this area. Soft tissue defects after tumor resection can be covered by a variety of local flaps. If local flaps are not applicable, free flap transfers, such as the anterolateral thigh (ALT) flap, parascapular flap or latissimus dorsi flap, can be utilized to cover nearly all kinds of defects in the foot and ankle region. Conclusion: Soft tissue reconstruction in the foot and ankle region is a vital component of limb-sparing surgery. It enables complete resection of locally advanced tumors and subsequent adjuvant radiotherapy. Modern plastic surgical techniques should, therefore, be integrated in the multimodal treatment concept of malignancies in the foot and ankle region

Angiogenesis in tissue engineering : Breathing life into constructed tissue substitutes

Long-term function of three-dimensional (3D) tissue constructs depends on adequate vascularization after implantation. Accordingly, research in tissue engineering has focused on the analysis of angiogenesis. For this purpose, 2 sophisticated in vivo models (the chorioallantoic membrane and the dorsal skinfold chamber) have recently been introduced in tissue engineering research, allowing a more detailed analysis of angiogenic dysfunction and engraftment failure. To achieve vascularization of tissue constructs, several approaches are currently under investigation. These include the modification of biomaterial properties of scaffolds and the stimulation of blood vessel development and maturation by different growth factors using slow-release devices through pre-encapsulated microspheres. Moreover, new microvascular networks in tissue substitutes can be engineered by using endothelial cells and stem cells or by creating arteriovenous shunt loops. Nonetheless, the currently used techniques are not sufficient to induce the rapid vascularization necessary for an adequate cellular oxygen supply. Thus, future directions of research should focus on the creation of microvascular networks within 3D tissue constructs in vitro before implantation or by co-stimulation of angiogenesis and parenchymal cell proliferation to engineer the vascularized tissue substitute in situ

Viral vector-mediated reprogramming of the fibroblastic tumor stroma sustains curative melanoma treatment.

The tumor microenvironment (TME) is a complex amalgam of tumor cells, immune cells, endothelial cells and fibroblastic stromal cells (FSC). Cancer-associated fibroblasts are generally seen as tumor-promoting entity. However, it is conceivable that particular FSC populations within the TME contribute to immune-mediated tumor control. Here, we show that intratumoral treatment of mice with a recombinant lymphocytic choriomeningitis virus-based vaccine vector expressing a melanocyte differentiation antigen resulted in T cell-dependent long-term control of melanomas. Using single-cell RNA-seq analysis, we demonstrate that viral vector-mediated transduction reprogrammed and activated a Cxcl13-expressing FSC subset that show a pronounced immunostimulatory signature and increased expression of the inflammatory cytokine IL-33. Ablation of Il33 gene expression in Cxcl13-Cre-positive FSCs reduces the functionality of intratumoral T cells and unleashes tumor growth. Thus, reprogramming of FSCs by a self-antigen-expressing viral vector in the TME is critical for curative melanoma treatment by locally sustaining the activity of tumor-specific T cells

The ParlaMint corpora of parliamentary proceedings

This paper presents the ParlaMint corpora containing transcriptions of the sessions of the 17 European national parliaments with half a billion words. The corpora are uniformly encoded, contain rich meta-data about 11 thousand speakers, and are linguistically annotated following the Universal Dependencies formalism and with named entities. Samples of the corpora and conversion scripts are available from the project’s GitHub repository, and the complete corpora are openly available via the CLARIN.SI repository for download, as well as through the NoSketch Engine and KonText concordancers and the Parlameter interface for on-line exploration and analysis

Untersuchungen zur Neovaskularisation und Degradation synthetischer PEGT/PBT-Block-Kopolymermatrizen nach Implantation in die transparente Rückenhautkammer von Balb/c-Mäusen

Problem: Die Funktion synthetischer Gewebeersatzmaterialien ist abhängig von der Vaskularisation. Methoden: PEGT/PBT-Block-Kopolymermatrizen (Scaffold-Implantat) mit 3 Porendiametern (1:<75$\mu$m, 2:75-212$\mu$m, 3:250-300$\mu$m) wurden in Rückenhautkammern von Balb/c-Mäusen (n=36) für 7, 14 u. 21 Tage implantiert. Nach histologischer Aufbereitung wurden apikale (AUF) und basale (BUF) Untersuchungsfelder (UF$\approx$0.047mm2, n=288) quantitativ lichtmikroskopisch analysiert. Digitale Bildanalyse der AUF und BUF zur Quantifizierung des Flächenverlustes wurde zusätzlich durchgeführt. Ergebnisse: 3 Wo nach Implantation wiesen Scaffold-Implantate der Porengrößen 75-212$\mu$m und 250-300$\mu$m eine profunde fibrovaskuläre Gewebsinfiltration auf. Kopolymermatrizen der Porengröße <75$\mu$m zeigten bildanalytisch einen progressiven Flächenverlust und exzessive Fragmnetierung der porösen Matrix. Diskussion: Die drei-dimensionale Struktur der porösen Scaffold-Implantate beeinflußt das Degradations- und Vaskularisationsverhalten

Improving Vascularization of Biomaterials for Skin and Bone Regeneration by Surface Modification: A Narrative Review on Experimental Research

Artificial tissue substitutes are of great interest for the reconstruction of destroyed and non-functional skin or bone tissue due to its scarcity. Biomaterials used as scaffolds for tissue regeneration are non-vascularized synthetic tissues and often based on polymers, which need ingrowth of new blood vessels to ensure nutrition and metabolism. This review summarizes previous approaches and highlights advances in vascularization strategies after implantation of surface-modified biomaterials for skin and bone tissue regeneration. The efficient integration of biomaterial, bioactive coating with endogenous degradable matrix proteins, physiochemical modifications, or surface geometry changes represents promising approaches. The results show that the induction of angiogenesis in the implant site as well as the vascularization of biomaterials can be influenced by specific surface modifications. The neovascularization of a biomaterial can be supported by the application of pro-angiogenic substances as well as by biomimetic surface coatings and physical or chemical surface activations. Furthermore, it was confirmed that the geometric properties of the three-dimensional biomaterial matrix play a central role, as they guide or even enable the ingrowth of blood vessels into a biomaterial