Challenges in developing a reseeded, tissue-engineered aortic valve prosthesis
| Autor: | Artur Lichtenberg, Alexander Hof, Laura Nehrenheim, Payam Akhyari, Silja Raschke, Heiko Meyer, Jessica I. Selig, Markus Schomaker, Karina Baier |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Scaffold Detergents 030204 cardiovascular system & hematology Extracellular matrix 03 medical and health sciences 0302 clinical medicine Bioreactors Tissue engineering Implants Experimental Cell Movement medicine.artery medicine Animals Trypsin Heart valve Cells Cultured Bioprosthesis Aorta Decellularization Sheep Tissue Engineering Tissue Scaffolds business.industry Lasers Models Cardiovascular Cell migration General Medicine Matrix Metalloproteinases Trypsinization Extracellular Matrix 030104 developmental biology medicine.anatomical_structure Aortic Valve Heart Valve Prosthesis Surgery Cardiology and Cardiovascular Medicine business |
| Zdroj: | European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 50(3) |
| ISSN: | 1873-734X |
| Popis: | Objectives Biological heart valve prostheses are characterized by a limited durability due to the degenerative processes after implantation. Tissue engineering may provide new approaches in the development of optimized valvular grafts. While re-endothelialization of decellularized heart valves has already been successfully implemented, interstitial repopulation still remains an unaccomplished objective although it is essential for valvular functionality and regeneration potential. The aim of this study was to compare different concepts for an improved in vitro interstitial repopulation of decellularized heart valves. A novel 3D heart valve model has been developed to investigate the cell behaviour of valvular interstitial cells (VIC) in their physiological environment and to evaluate the potential of in vitro repopulation of acellular heart valves. Methods Ovine aortic heart valves were decellularized by detergent solutions and additionally treated with trypsin or laser perforation. Subsequently, the decellularized extracellular matrices (dECM) were reseeded with ovine VIC using reseeding devices to provide a repopulation of the matrix on a defined area under controlled conditions. After an initial attachment of the VIC, reseeded dECM were transferred into a transwell system to improve the nutrient supply inside the valvular matrix. Cell migration and expression of cell markers were analysed histologically. The results were compared with VIC cultivation in a biological scaffold. Results VIC did not migrate into the matrix of untreated dECM and reseeding in laser perforated dECM showed inconsistent results. However, trypsinization increased the susceptibility of the valvular cusps to VIC penetration and repopulation of superficial areas. Additionally, the cultivation of reseeded dECM in a transwell system significantly increased the total number of cells repopulating the valvular matrix and their mean migration distance, representing the best repopulation results. Immunohistological analysis and in situ zymography revealed a low activation status of repopulating VIC after 7 days of culture. Conclusions A comparison of different techniques for increasing interstitial repopulation of detergent dECM revealed that an additional limited trypsin treatment was most effective. Nevertheless, a complete interstitial repopulation of decellularized heart valves remains a challenging endeavour. Additional experimental fine-tuning may improve the in vitro results of heart valve tissue engineering. |
| Databáze: | OpenAIRE |
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