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Rapid Specialization and Stiffening of the Primitive Matrix in Developing Articular Cartilage and Meniscus
Journal article   Open access   Peer reviewed

Rapid Specialization and Stiffening of the Primitive Matrix in Developing Articular Cartilage and Meniscus

Bryan Kwok, Prashant Chandrasekaran, Chao Wang, Lan He, Robert L. Mauck, Nathaniel A. Dyment, Eiki Koyama and Lin Han
Acta biomaterialia
04 Jul 2023
DOI: https://doi.org/10.1016/j.actbio.2023.06.047
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

articular cartilage embryonic development meniscus nanomechanics primitive matrix
Understanding early patterning events in extracellular matrix (ECM) formation can provide a blueprint for regenerative strategies to better recapitulate the function of native tissues. Currently, there is little knowledge on the initial, incipient ECM of articular cartilage and meniscus, two load-bearing counterparts of the knee joint. This study elucidated distinctive traits of their developing ECMs by studying the composition and biomechanics of these two tissues in mice from mid-gestation (embryonic day 15.5) to neo-natal (post-natal day 7) stages. We show that articular cartilage initiates with the formation of a pericellular matrix (PCM)-like primitive matrix, followed by the separation into distinct PCM and territorial/interterritorial (T/IT)-ECM domains, and then, further expansion of the T/IT-ECM through maturity. In this process, the primitive matrix undergoes a rapid, exponential stiffening, with a daily modulus increase rate of 35.7% [31.9.39.6]% (mean [95%.CI]). Meanwhile, the matrix becomes more heterogeneous in the spatial distribution of properties, with concurrent exponential increases in the standard deviation of micromodulus and the slope correlating local micromodulus with the distance from cell surface. In comparison to articular cartilage, the primitive matrix of meniscus also exhibits exponential stiffening and an increase in heterogeneity, albeit with a much slower daily stiffening rate of 19.8% [14.9.24.9]% and a delayed separation of PCM and T/IT-ECM. These contrasts underscore distinct development paths of hyaline versus fibrocartilage. Collectively, these findings provide new insights into how knee joint tissues form to better guide cell- and biomaterial-based repair of articular cartilage, meniscus and potentially other load-bearing cartilaginous tissues. Successful regeneration of articular cartilage and meniscus is challenged by incomplete knowledge of early events that drive the initial formation of the tissues’ extracellular matrix in vivo. This study shows that articular cartilage initiates with a pericellular matrix (PCM)-like primitive matrix during embryonic development. This primitive matrix then separates into distinct PCM and territorial/interterritorial domains, undergoes an exponential daily stiffening of ∼36% and an increase in micromechanical heterogeneity. At this early stage, the meniscus primitive matrix shows differential molecular traits and exhibits a slower daily stiffening of ∼20%, underscoring distinct matrix development between these two tissues. Our findings thus established a new blueprint to guide the design of regenerative strategies to recapitulate the key developmental steps in vivo. [Display omitted]

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8 citations in Web of Science
7 citations in Scopus

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Engineering, Biomedical
Materials Science, Biomaterials
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