Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Tissue Eng Part A. 2012 Feb;18(3-4):221-31. doi: 10.1089/ten.TEA.2010.0658. Epub 2011 Oct 11.
Cardiovascular tissue engineering has shown considerable progress, but in vitro tissue conditioning to stimulate the development of a functional extracellular matrix still needs improvement. We investigated the environmental factor oxygen concentration for its potential to increase the amount of collagen and collagen cross-links, and therefore improve tissue quality. Cardiovascular tissue engineered (TE) constructs, made of rapidly degrading PGA/P4HB scaffold seeded with human vascular-derived cells, were cultured at 7%, 4%, 2%, 0.5% O(2) for 4 weeks and compared to control cultures at 21% O(2). Tissue properties were evaluated by measuring the extracellular matrix production and mechanical behavior. The culture environment was monitored closely and the oxygen gradient throughout the constructs was simulated with a theoretical model. TE constructs cultured at 21%, 7% and 4% O(2) showed dense and homogeneous tissue formation with comparable strength, stiffness, collagen and collagen cross-link content. At 2% O(2), collagen content and stiffness decreased, whereas at 0.5% O(2), hardly any tissue was formed. Overall, tissue properties deteriorated at the lowest oxygen concentrations, opposing our hypothesis that was based on previous culture at low oxygen concentrations. Further research will focus on establishing the balance between applied oxygen conditions (concentration and exposure time) and optimal tissue outcome.
心血管组织工程已经取得了相当大的进展，但体外组织培养以刺激功能性细胞外基质的发育仍需要改进。我们研究了环境因素氧浓度，以增加胶原蛋白和胶原蛋白交联的数量，从而改善组织质量。用快速降解的 PGA/P4HB 支架培养的人血管源性细胞，在 7%、4%、2%、0.5%的 O(2)下培养 4 周，并与 21%的 O(2)下的对照培养物进行比较。通过测量细胞外基质的产生和力学行为来评估组织特性。密切监测培养环境，并通过理论模型模拟整个构建体中的氧梯度。在 21%、7%和 4%的 O(2)下培养的 TE 构建体具有致密且均匀的组织形成，具有可比的强度、刚度、胶原蛋白和胶原蛋白交联含量。在 2%的 O(2)下，胶原蛋白含量和刚度降低，而在 0.5%的 O(2)下，几乎没有形成组织。总的来说，在最低氧浓度下，组织特性恶化，与我们基于先前低氧浓度培养的假设相反。进一步的研究将集中在建立应用氧条件（浓度和暴露时间）和最佳组织结果之间的平衡。
