Kartogenin Enhances Chondrogenic Differentiation of MSCs in 3D Tri-Copolymer Scaffolds and the Self-Designed Bioreactor System.

Ching-Yun Chen,Cherng-Jyh Ke,Chunching Li,Feng-Huei Lin,Jui-Sheng Sun

doi:10.3390/biom11010115

Abstract

Human cartilage has relatively slow metabolism compared to other normal tissues. Cartilage damage is of great clinical consequence since cartilage has limited intrinsic healing potential. Cartilage tissue engineering is a rapidly emerging field that holds great promise for tissue function repair and artificial/engineered tissue substitutes. However, current clinical therapies for cartilage repair are less than satisfactory and rarely recover full function or return the diseased tissue to its native healthy state. Kartogenin (KGN), a small molecule, can promote chondrocyte differentiation both in vitro and in vivo. The purpose of this research is to optimize the chondrogenic process in mesenchymal stem cell (MSC)-based chondrogenic constructs with KGN for potential use in cartilage tissue engineering. In this study, we demonstrate that KGN treatment can promote MSC condensation and cell cluster formation within a tri-copolymer scaffold. Expression of Acan, Sox9, and Col2a1 was significantly up-regulated in three-dimensional (3D) culture conditions. The lacuna-like structure showed active deposition of type II collagen and aggrecan deposition. We expect these results will open new avenues for the use of small molecules in chondrogenic differentiation protocols in combination with scaffolds, which may yield better strategies for cartilage tissue engineering.

Highlights

Tri-copolymer scaffold was imaged by Scanning electron microscopy (SEM) after cross-linking and lyophilization
We studied the differentiation of rat mesenchymal stem cells (rMSCs) under different conditions
21-days cultivation; (A3) and the content of glycosaminoglycans (GAGs) secreted into the cultured medium within the cell cluster was clearly demonstrated after 21-days cultivation; (A3) and the content of was measured by dimethylmethylene blue (DMMB) assay, we found that the GAGs contents were signifiglycosaminoglycans secreted into the cultured medium was measured by dimethylmethylene cantly increased with the longer culture period.(GAGs)

Summary

Introduction

Avascular, alymphatic, and hypocellular tissue, articular (hyaline) cartilage has been the primary focus of most clinicians. The dry weight of articular cartilage is mainly composed of type II collagen and proteoglycans, which provide load-bearing function [1]. Chondrogenic tissues in normal conditions have a relatively slow potential of healing; damage to cartilage is of great clinical concern since the cartilage tissue has limited intrinsic healing potential. Cartilage lesions arising due to aging, joint laxity, excessive stress imposed upon normal tissue, diet, hormones, crystal deposition, bone microfractures, and immunologic factors have been implicated in the etiopathogenesis of osteoarthritis [2]. Osteoarthritis (OA) is not the result of diminished metabolic activity; on the contrary, it is a Biomolecules 2021, 11, 115.

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