Comparison of Chondrocytes in Knee Osteoarthritis and Regulation by Scaffold Pore Size and Stiffness

Abstract

In knee osteoarthritis (OA), there is more pronounced cartilage damage in the medial compartment (“lesion zone”) than the lateral compartment (“remote zone”). This study fills a gap in the literature by conducting a systematic comparison of cartilage and chondrocyte characteristics from these two zones. It also investigates whether chondrocytes from the different zones respond distinctly to changes in the physical and mechanical microenvironment using three-dimensional porous scaffolds by changing stiffness and pore size. Cartilage was harvested from patients with end-stage varus knee OA. Cartilage from the lesion and remote zones were compared through histological and biomechanical assessments, and through proteomic and gene transcription analyses of chondrocytes. Gelatin scaffolds with varied pore sizes and stiffness were used to investigate in vitro microenvironmental regulation of chondrocytes from the two zones. Cartilage from the lesion and remote zones differed significantly (p < 0.05) in histological and biomechanical characteristics, as well as phenotype, protein, and gene expression of chondrocytes. Chondrocytes from both zones were sensitive to changes in the structural and mechanical properties of gelatin scaffolds. Of interest, although all chondrocytes better retained chondrocyte phenotype in stiffer scaffolds, those from the lesion and remote zones, respectively, preferred scaffolds with larger and smaller pores. Distinct variations exist in cartilage and chondrocyte characteristics in the lesion and remote zones of knee OA. Cells in these two zones respond differently to variations in the physical and mechanical microenvironment. Understanding and manipulating these differences will facilitate the development of more efficient and precise diagnostic and therapeutic approaches for knee OA.

Impact statement

This study performs a novel systematic analysis of cartilage properties in the lesion (medial) and remote (lateral) zones of knee osteoarthritis (OA), from the tissue level right down to the cell and molecular levels. It also demonstrates for the first time the effects of manipulating the physical and mechanical microenvironment on the behavior of chondrocytes from the lesion and remote zones. This study improves our understanding of the properties and responses of tissues and cells in different zones of knee OA, providing novel insights into OA pathophysiology and also demonstrating a new application of biomaterial scaffolds in studying cell–matrix interactions.