Design and efficacy of a single-use bioreactor for heart valve tissue engineering

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• 作者：Gabriel L. Converse ; Eric E. Buse ; Kari R. Neill ; Christopher R. McFall ; Holley N. Lewis ; Mitchell C. VeDepo ; Rachael W. Quinn and Richard A. Hopkins
• 刊名：Journal of Biomedical Materials Research Part B: Applied Biomaterials
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：105
• 期：2
• 页码：249-259
• 全文大小：901K
• ISSN：1552-4981

文摘

Heart valve tissue engineering offers the promise of improved treatments for congenital heart disorders; however, widespread clinical availability of a tissue engineered heart valve (TEHV) has been hindered by scientific and regulatory concerns, including the lack of a disposable, bioreactor system for nondestructive valve seeding and mechanical conditioning. Here we report the design for manufacture and the production of full scale, functional prototypes of such a system. To evaluate the efficacy of this bioreactor as a tool for seeding, ovine aortic valves were decellularized and subjected to seeding with human mesenchymal stem cells (hMSC). The effects of pulsatile conditioning using cyclic waveforms tuned to various negative and positive chamber pressures were evaluated, with respect to the seeding of cells on the decellularized leaflet and the infiltration of seeded cells into the interstitium of the leaflet. Infiltration of hMSCs into the aortic valve leaflet was observed following 72 h of conditioning under negative chamber pressure. Additional conditioning under positive pressure improved cellular infiltration, while retaining gene expression within the MSC-valve interstitial cell phenotype lineage. This protocol resulted in a subsurface pilot population of cells, not full tissue recellularization.