钙化性变性是最常见的心脏瓣膜衰竭类型,由于人口老龄化,发病率上升。迄今为止的黄金标准治疗是瓣膜置换。不幸的是,钙化经常发生在生物假体替代品中,对治理过程知之甚少。这里,我们提出了一个多尺度,在完整的组织解剖学背景下,失败的生物假体牛心包瓣膜外植体中胶原蛋白网络的干扰和广泛矿化的多模态分析。除了高度丰富的矿化胶原纤维和原纤维,先前在天然瓣膜中发现的钙化微米级颗粒也普遍存在于生物人工瓣膜的主动脉和心室表面。两种矿物类型(纤维和颗粒)即使在早期矿化中也可以检测到,在任何宏观钙化之前。基于多尺度多模态表征和高保真仿真,我们证明,矿物质的发生与暴露于高血液动力学和生物力学指标的区域一致。通过对失败的生物人工瓣膜进行多尺度分析获得的这些见解可能为基于证据的更持久替代品的开发奠定了基础。意义声明:生物瓣膜钙化是一种众所周知的临床重要现象,导致阀门失效。生物人工瓣膜的纳米分析表征提供了对高度丰富的见解,胶原蛋白网络的广泛钙化和解体,以及先前在天然心血管组织中报道的磷酸钙颗粒的存在。虽然胶原基质矿化主要归因于化学和机械改变的组合,钙化颗粒可能来自宿主细胞。这项工作提出了一个简单的路线,以高分辨率和灵敏度进行矿物识别和表征,在完整的组织解剖学背景下,因此提供了改进的生物人工瓣膜替代品的设计线索。
Calcific degeneration is the most frequent type of heart valve failure, with rising incidence due to the ageing population. The gold standard treatment to date is valve replacement. Unfortunately, calcification oftentimes re-occurs in bioprosthetic substitutes, with the governing processes remaining poorly understood. Here, we present a multiscale, multimodal analysis of disturbances and extensive mineralisation of the collagen network in failed bioprosthetic bovine pericardium valve explants with full histoanatomical context. In addition to highly abundant mineralized collagen fibres and fibrils, calcified micron-sized particles previously discovered in native valves were also prevalent on the aortic as well as the ventricular surface of bioprosthetic valves. The two mineral types (fibres and particles) were detectable even in early-stage mineralisation, prior to any macroscopic calcification. Based on multiscale multimodal characterisation and high-fidelity simulations, we demonstrate that mineral occurrence coincides with regions exposed to high haemodynamic and biomechanical indicators. These insights obtained by multiscale analysis of failed bioprosthetic valves serve as groundwork for the evidence-based development of more durable alternatives. STATEMENT OF SIGNIFICANCE: Bioprosthetic valve calcification is a well-known clinically significant phenomenon, leading to valve failure. The nanoanalytical characterisation of bioprosthetic valves gives insights into the highly abundant, extensive calcification and disorganization of the collagen network and the presence of calcium phosphate particles previously reported in native cardiovascular tissues. While the collagen matrix mineralisation can be primarily attributed to a combination of chemical and mechanical alterations, the calcified particles are likely of host cellular origin. This work presents a straightforward route to mineral identification and characterization at high resolution and sensitivity, and with full histoanatomical context and correlation to hemodynamic and biomechanical indicators, hence providing design cues for improved bioprosthetic valve alternatives.