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• W112584510 abstract "Introduction: For two decades, bioartificial human tissues are engineered for the reconstruction and replacement of damaged tissues and organs (Tissue Engineering). The generation of complex tissues suitable for reconstructive surgery, however, failed due to unavailable implant vascularization. In continuation of pre-clinical studies, we developed a bioartificial transplant for clinical applications that is endued with a private vascular system and can be connected to the recipient vascularization. Material and methods: In a patient with a large tracheo-esophageal fistula human fibroblasts and muscle cells were isolated form a muscle biopsy and cultured corresponding to GMP regulations for 6 weeks. Peripheral blood mononuclear cells (PBMC) were isolated from a blood sample (400 ml). For implant generation, a porcine jejunal segment including its afferent artery and efferent vein was explanted and decellularized. Human PBMC were seeded on the preserved basal membrane within the cell-free vascular system applying pulsatile media-flow. Endothelial differentiation was confirmed immunhistochemically by CD34, CD31 and VE cadherin, expression. Within 14 days, an autologous human vascular system formed. Thereupon, the implant was seeded with human fibroblasts and muscle cells. To verify vascular function and implant vitality, the bioartificial construct was implanted into the left upper arm of the patient and connected to the brachial vascular bundle. After one week, the bioartificial tissue was explanted on schedule to assess vascular permeability, tissue integrity and vitality. For reconstruction of the tracheo-esophageal defect an identical bioartificial implant was generated. Results: Implant generation lasted 5 weeks. The bioartificial implant was endued with a closed vascular circuit, which was connected to the patient’s vascular system using established surgical techniques. Aggressive clinical anticoagulation protocols applying heparin and aspirin were effectual to maintain implant patency. During surgical im- and explantation, a venous backflow was confirmed in the arterially connected implant. Histopathological work up supported implant vitality and a continuing functional and intact endothelial lining. There was no evidence of inflammation or tissue rejection at the implantation site. Conclusions: Pre-clinical Tissue Engineering techniques were successfully transferred into the clinical setting. The generated bioartificial tissue is viable following transplantation. It may represent a starting basis for the clinical application of numerous engineered repair tissues for reconstructive surgery in numerous paediatric and adult pathologies. In the long run, it may serve for the generation of highly sophisticated repair tissues such as endocrine pancreas." @default.
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• W112584510 date "2009-01-01" @default.
• W112584510 modified "2023-09-26" @default.
• W112584510 title "Bioartificial vascularized human tissues as implants for reconstructive surgery: Implant generation and first clinical results" @default.
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• W112584510 doi "https://doi.org/10.1007/978-3-642-00625-8_101" @default.
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