School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USA.
Adv Exp Med Biol. 2023;1402:69-82. doi: 10.1007/978-3-031-25588-5_5.
Articular cartilage is a hydrated macromolecular composite mainly composed of type II collagen fibrils and the large proteoglycan, aggrecan. Aggrecan is a key determinant of the load bearing and energy dissipation functions of cartilage. Previously, studies of cartilage biomechanics have been primarily focusing on the macroscopic, tissue-level properties, which failed to elucidate the molecular-level activities that govern cartilage development, function, and disease. This chapter provides a brief summary of Dr. Alan J. Grodzinsky's seminal contribution to the understanding of aggrecan molecular mechanics at the nanoscopic level. By developing and applying a series of atomic force microscopy (AFM)-based nanomechanical tools, Grodzinsky and colleagues revealed the unique structural and mechanical characteristics of aggrecan at unprecedented resolutions. In this body of work, the "bottle-brush"-like ultrastructure of aggrecan was directly visualized for the first time. Meanwhile, molecular mechanics of aggrecan was studied using a physiological-like 2D biomimetic assembly of aggrecan on multiple fronts, including compression, dynamic loading, shear, and adhesion. These studies not only generated new insights into the development, aging, and disease of cartilage, but established a foundation for designing and evaluating novel cartilage regeneration strategies. For example, building on the scientific foundation and methodology infrastructure established by Dr. Grodzinsky, recent studies have elucidated the roles of other proteoglycans in mediating cartilage integrity, such as decorin and perlecan, and evaluated the therapeutic potential of biomimetic proteoglycans in improving cartilage regeneration.
关节软骨是一种富含水分的高分子复合材料，主要由 II 型胶原纤维和大型蛋白聚糖聚集蛋白聚糖组成。聚集蛋白聚糖是软骨承载和能量耗散功能的关键决定因素。先前，软骨生物力学的研究主要集中在宏观、组织层面的特性上，未能阐明控制软骨发育、功能和疾病的分子水平活动。本章简要总结了 Alan J. Grodzinsky 博士在纳米尺度上理解聚集蛋白聚糖分子力学方面的开创性贡献。通过开发和应用一系列原子力显微镜 (AFM) 纳米力学工具，Grodzinsky 及其同事以前所未有的分辨率揭示了聚集蛋白聚糖独特的结构和力学特性。在这项工作中，首次直接观察到了聚集蛋白聚糖的“瓶刷”状超微结构。同时，通过多方面的研究，包括压缩、动态加载、剪切和粘附，研究了聚集蛋白聚糖的分子力学。这些研究不仅为软骨的发育、衰老和疾病提供了新的见解，而且为设计和评估新型软骨再生策略奠定了基础。例如，在 Grodzinsky 博士建立的科学基础和方法学基础设施的基础上，最近的研究阐明了其他蛋白聚糖在介导软骨完整性方面的作用，如 decorin 和 perlecan，并评估了仿生蛋白聚糖在改善软骨再生方面的治疗潜力。
