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

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.

A Dual-Factor Releasing Hydrogel for Rotator Cuff Injury Repair

“…Accelerating the regeneration of fibrocartilage is important to promote rotator cuff healing (Zhu et al, 2021). As a synthetic compound, KGN has been shown to promote cartilage tissue regeneration in vitro and in vivo (Hong et al, 2020;Chen et al, 2021;Hou et al, 2021;Zhu et al, 2021). Johnson et al used KGN to repair articular cartilage defects in mice and found that KGN could induce cartilage formation through the CBFβ-RUNX1 pathway (Johnson et al, 2012).…”

“…It can also bind to the core binding factor subunit β (CBF-β), promote the entry of CBF-β into the nucleus, and combine with the DNA transcription factor RUNX1 to form a dimer, thus activating some genes that promote the chondrogenesis of stem cells (Jing et al, 2019). In vitro and in vivo studies have proved that KGN can effectively promote the differentiation of MSCs from various sources into chondrocytes, thus promoting the regeneration of cartilage at the tendon-bone interface (Wang et al, 2018;Chen et al, 2021;Shao et al, 2021;Zhu et al, 2021). Fibroblast growth factor (FGF) is a family of 23 structure-related peptides that play an important role in angiogenesis and mesenchymal cell mitosis.…”

3D Bioprinting of Hydrogels for Cartilage Tissue Engineering

“…New growth factors have been discovered in recent years, such as platelet concentrates [ 33 ] and small molecules, such as kartogenin (KGN) [ 34 , 35 ] and dexamethasone, that can regulate biological processes, promote the survival and proliferation of cells, and maintain the differentiated phenotype.…”

Targeted treatment for osteoarthritis: drugs and delivery system

“…The KGN-loaded NPPs improved chondrohistology and osteophyte size in vivo test. In the past two years, tri-copolymer scaffolds structured by gelatin-chondroitin-hyaluronan and engineered exosomes were used to deliver KGN to chondrocytes and showed potential application future (Chen et al., 2021 ; Xu et al., 2021 ).…”