Cartilage Extracellular Matrix Scaffold With Kartogenin-Encapsulated PLGA Microspheres for Cartilage Regeneration.

Yanhong Zhao,Min Wang,Ying Huang,Xintong Zhong,Yunjie Li,Yanmei Zhao,Xige Zhao,Yang Zhang,Minhui Shan,Yi Xing,Rui Zhang

doi:10.3389/fbioe.2020.600103

Abstract

Repair of articular cartilage defects is a challenging aspect of clinical treatment. Kartogenin (KGN), a small molecular compound, can induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. Here, we constructed a scaffold based on chondrocyte extracellular matrix (CECM) and poly(lactic-co-glycolic acid) (PLGA) microspheres (MP), which can slowly release KGN, thus enhancing its efficiency. Cell adhesion, live/dead staining, and CCK-8 results indicated that the PLGA(KGN)/CECM scaffold exhibited good biocompatibility. Histological staining and quantitative analysis demonstrated the ability of the PLGA(KGN)/CECM composite scaffold to promote the differentiation of BMSCs. Macroscopic observations, histological tests, and specific marker analysis showed that the regenerated tissues possessed characteristics similar to those of normal hyaline cartilage in a rabbit model. Use of the PLGA(KGN)/CECM scaffold may mimic the regenerative microenvironment, thereby promoting chondrogenic differentiation of BMSCs in vitro and in vivo. Therefore, this innovative composite scaffold may represent a promising approach for acellular cartilage tissue engineering.

Highlights

Because of its avascular, alymphatic, and aneural properties, articular cartilage has poor spontaneous repair and regeneration capabilities (Malfait, 2016)
KGN has been investigated as a cartilage-promoting molecule, two common models of KGN application remain problematic: (1) direct injection into the joint cavity, (Xu et al, 2015; Kwon et al, 2018) which is ineffective because most KGN is absorbed by the circulatory system and repeated injections increase both pain and risk of infection; (2) combination of KGN with drug delivery system: such as hydrogel (Wang S.J. et al, 2019), platelet-rich plasma (PRP)(Liu et al, 2019), nanoparticles, or microspheres (Kang et al, 2014)
Quantitative analysis revealed that the mean pore diameter was 140 μm (Figure 2A), which met the requirements for use in cartilage tissue engineering

Summary

Introduction

Alymphatic, and aneural properties, articular cartilage has poor spontaneous repair and regeneration capabilities (Malfait, 2016). Previous studies have focused on cartilage stimulation methods that support the capacity for self-repair. Signaling molecules, such as transforming growth factor beta-3 (TGF-β3), have been widely used as chondrogenic modulators (Mi et al, 2003; van der Kraan and van den Berg, 2007; Cals et al, 2012; Almeida et al, 2014). During mesenchymal stem cell (MSC) differentiation, KGN frees CBFβ, which binds to the transcription factor RUNX1. Several drug delivery systems have been used to achieve sustained release of KGN, the potential application of KGN in cartilage tissue engineering is seldom investigated, and additional mesenchymal stem cells implantation are needed (Li et al, 2016; Wang J. et al, 2019). The amino groups of PLGA can bind covalently to the carboxyl groups of KGN, enhancing the permeability and retention of KGN and promoting its therapeutic effects (Kang et al, 2014; Fan et al, 2018; Chen et al, 2020)

Methods

Results

Conclusion