Oomen P J A, Loerakker S, van Geemen D, Neggers J, Goumans M-J T H, van den Bogaerdt A J, Bogers A J J C, Bouten C V C, Baaijens F P T
Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600MB Eindhoven, Netherlands; Department of Biomedical Engineering, Eindhoven University of Technology, 5600MB Eindhoven, Netherlands.
Department of Biomedical Engineering, Eindhoven University of Technology, 5600MB Eindhoven, Netherlands.
Acta Biomater. 2016 Jan;29:161-169. doi: 10.1016/j.actbio.2015.10.044. Epub 2015 Nov 6.
In order to create tissue-engineered heart valves with long-term functionality, it is essential to fully understand collagen remodeling during neo-tissue formation. Collagen remodeling is thought to maintain mechanical tissue homeostasis. Yet, the driving factor of collagen remodeling remains unidentified. In this study, we determined the collagen architecture and the geometric and mechanical properties of human native semilunar heart valves of fetal to adult age using confocal microscopy, micro-indentation and inverse finite element analysis. The outcomes were used to predict age-dependent changes in stress and stretch in the heart valves via finite element modeling. The results indicated that the circumferential stresses are different between the aortic and pulmonary valve, and, moreover, that the stress increases considerably over time in the aortic valve. Strikingly, relatively small differences were found in stretch with time and between the aortic and pulmonary valve, particularly in the circumferential direction, which is the main determinant of the collagen fiber stretch. Therefore, we suggest that collagen remodeling in the human heart valve maintains a stretch-driven homeostasis. Next to these novel insights, the unique human data set created in this study provides valuable input for the development of numerical models of collagen remodeling and optimization of tissue engineering.
Annually, over 280,000 heart valve replacements are performed worldwide. Tissue engineering has the potential to provide valvular disease patients with living valve substitutes that can last a lifetime. Valve functionality is mainly determined by the collagen architecture. Hence, understanding collagen remodeling is crucial for creating tissue-engineered valves with long-term functionality. In this study, we determined the structural and material properties of human native heart valves of fetal to adult age to gain insight into the mechanical stimuli responsible for collagen remodeling. The age-dependent evolutionary changes in mechanical state of the native valve suggest that collagen remodeling in heart valves is a stretch-driven process.
为了制造具有长期功能的组织工程心脏瓣膜，充分了解新组织形成过程中的胶原蛋白重塑至关重要。胶原蛋白重塑被认为可维持组织机械稳态。然而，胶原蛋白重塑的驱动因素仍未明确。在本研究中，我们使用共聚焦显微镜、微压痕和逆有限元分析确定了从胎儿到成人阶段的人类天然半月形心脏瓣膜的胶原蛋白结构以及几何和力学特性。通过有限元建模，利用这些结果预测心脏瓣膜中应力和拉伸随年龄的变化。结果表明，主动脉瓣和肺动脉瓣的周向应力不同，而且，主动脉瓣中的应力随时间显著增加。令人惊讶的是，在拉伸随时间的变化以及主动脉瓣和肺动脉瓣之间，尤其是在圆周方向（胶原蛋白纤维拉伸的主要决定因素）上发现相对较小的差异。因此，我们认为人类心脏瓣膜中的胶原蛋白重塑维持了拉伸驱动的稳态。除了这些新见解之外，本研究中创建的独特人类数据集为胶原蛋白重塑数值模型的开发和组织工程优化提供了有价值的输入。
全球每年进行超过28万例心脏瓣膜置换手术。组织工程有潜力为瓣膜疾病患者提供可终身使用的活体瓣膜替代品。瓣膜功能主要由胶原蛋白结构决定。因此，了解胶原蛋白重塑对于制造具有长期功能的组织工程瓣膜至关重要。在本研究中，我们确定了从胎儿到成人阶段的人类天然心脏瓣膜的结构和材料特性，以深入了解负责胶原蛋白重塑的机械刺激。天然瓣膜机械状态随年龄的进化变化表明，心脏瓣膜中的胶原蛋白重塑是一个拉伸驱动的过程。
