Anke Wixmerten

Universität Basel, Bâle, Basel-City, Switzerland

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Publications (4)46.9 Total impact

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    ABSTRACT: Autologous native cartilage from the nasal septum, ear, or rib is the standard material for surgical reconstruction of the nasal alar lobule after two-layer excision of non-melanoma skin cancer. We assessed whether engineered autologous cartilage grafts allow safe and functional alar lobule restoration. In a first-in-human trial, we recruited five patients at the University Hospital Basel (Basel, Switzerland). To be eligible, patients had to be aged at least 18 years and have a two-layer defect (≥50% size of alar subunit) after excision of non-melanoma skin cancer on the alar lobule. Chondrocytes (isolated from a 6 mm cartilage biopsy sample from the nasal septum harvested under local anaesthesia during collection of tumour biopsy sample) were expanded, seeded, and cultured with autologous serum onto collagen type I and type III membranes in the course of 4 weeks. The resulting engineered cartilage grafts (25 mm × 25 mm × 2 mm) were shaped intra-operatively and implanted after tumour excision under paramedian forehead or nasolabial flaps, as in standard reconstruction with native cartilage. During flap refinement after 6 months, we took biopsy samples of repair tissues and histologically analysed them. The primary outcomes were safety and feasibility of the procedure, assessed 12 months after reconstruction. At least 1 year after implantation, when reconstruction is typically stabilised, we assessed patient satisfaction and functional outcomes (alar cutaneous sensibility, structural stability, and respiratory flow rate). Between Dec 13, 2010, and Feb 6, 2012, we enrolled two women and three men aged 76-88 years. All engineered grafts contained a mixed hyaline and fibrous cartilage matrix. 6 months after implantation, reconstructed tissues displayed fibromuscular fatty structures typical of the alar lobule. After 1 year, all patients were satisfied with the aesthetic and functional outcomes and no adverse events had been recorded. Cutaneous sensibility and structural stability of the reconstructed area were clinically satisfactory, with adequate respiratory function. Autologous nasal cartilage tissues can be engineered and clinically used for functional restoration of alar lobules. Engineered cartilage should now be assessed for other challenging facial reconstructions. Foundation of the Department of Surgery, University Hospital Basel; and Krebsliga beider Basel.
    The Lancet 04/2014; · 39.21 Impact Factor
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    ABSTRACT: Since the late 1960s, surgeons and scientists envisioned use of tissue engineering to provide an alternative treatment for tissue and organ damage by combining biological and synthetic components in such a way that a long-lasting repair was established. In addition to the treatment, the patient would also benefit from reduced donor site morbidity and operation time as compared with the standard procedures. Tremendous efforts in basic research have been done since the late 1960s to better understand chondrocyte biology and cartilage maturation and to fulfill the growing need for tissue-engineered cartilage in reconstructive, trauma, and orthopedic surgery. Starting from the first successful generation of engineered cartilaginous tissue, scientists strived to improve the properties of the cartilaginous constructs by characterizing different cell sources, modifying the environmental factors influencing cell expansion and differentiation and applying physical stimuli to modulate the mechanical properties of the construct. All these efforts have finally led to a clinical phase I trial to show the safety and feasibility of using tissue-engineered cartilage in reconstructive facial surgery. However, to bring tissue engineering into routine clinical applications and commercialize tissue-engineered grafts, further research is necessary to achieve a cost-effective, standardized, safe, and regulatory compliant process.
    Facial Plastic Surgery 04/2013; 29(2):99-105. · 0.92 Impact Factor
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    ABSTRACT: This study was designed to determine if the maturation stage of engineered cartilage implanted in a goat model of cartilage injury influences the repair outcome. Goat engineered cartilage was generated from autologous chondrocytes cultured in hyaluronic acid scaffolds using 2 d, 2 weeks or 6 weeks of pre-culture and implanted above hydroxyapatite/hyaluronic acid sponges into osteochondral defects. Control defects were left untreated or treated with cell-free scaffolds. The quality of repair tissues was assessed 8 weeks or 8 months post implantation by histological staining, modified O'Driscoll scoring and biochemical analyses. Increasing pre-culture time resulted in progressive maturation of the grafts in vitro. After 8 weeks in vivo, the quality of the repair was not improved by any treatment. After 8 months, O'Driscoll histology scores indicated poor cartilage architecture for untreated (29.7 ± 1.6) and cell-free treated groups (24.3 ± 5.8). The histology score was improved when cellular grafts were implanted, with best scores observed for grafts pre-cultured for 2 weeks (16.3 ± 5.8). As compared to shorter pre-culture times, grafts cultured for 6 weeks (histology score: 22.3 ± 6.4) displayed highest type II/I collagen ratios but also inferior architecture of the surface and within the defect, as well as lower integration with native cartilage. Thus, pre-culture of engineered cartilage for 2 weeks achieved a suitable compromise between tissue maturity and structural/integrative properties of the repair tissue. The data demonstrate that the stage of development of engineered cartilage is an important parameter to be considered in designing cartilage repair strategies.
    European cells & materials 01/2012; 23:222-36. · 4.89 Impact Factor
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    Karoliina Pelttari, Anke Wixmerten, Ivan Martin
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    ABSTRACT: The in vitro engineering of functionally developed biological cartilage substitutes, based on cells and appropriate structural and soluble factors, is an attractive concept for the clinical treatment of cartilage injuries and degeneration. The field of cartilage tissue engineering has developed strongly in the last few years, bringing together the scientific, clinical and commercial interests of highly interdisciplinary communities. However, engineered grafts are still far from being the standard of care for cartilage repair. In this review we present some of the issues challenging the reproducible engineering of functional cartilage templates starting from human cells. We then discuss the need to identify the mode of action of cartilage tissue engineering approaches, which in turn is expected to define potency markers and quality controls for grafts capable of inducing durable cartilage regeneration. Finally, we propose the use of engineered cartilage tissues not only as implants to be implemented in the clinic, but also as models to understand mechanisms and processes related to cartilage development and repair. The knowledge generated using these models will be instrumental in moving to the next generation of cartilage repair approaches, namely those inducing regeneration in situ, based on the recruitment of resident cells.
    Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology 10/2009; 139(41-42):602-9. · 1.88 Impact Factor