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

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.

3D Printed Poly(ε-Caprolactone)/Meniscus Extracellular Matrix Composite Scaffold Functionalized With Kartogenin-Releasing PLGA Microspheres for Meniscus Tissue Engineering

“…KGN has raised much attention in cartilaginous tissue engineering due to its favorable stability, cartilage protective effects, and strong chondrogenic ability (Johnson et al, 2012). However, to avoid the side effects and unwanted circulatory clearance, an ideal delivery platform that fully utilized the KGN to provide sustained chondrogenic induction is required (Zhao et al, 2020). PLGA µS were good drug carriers and capable of sustaining and localizing delivery of bioactive drugs to dictate surrounding cell behaviors (Asgari et al, 2020;Zhao et al, 2020).…”

“…However, to avoid the side effects and unwanted circulatory clearance, an ideal delivery platform that fully utilized the KGN to provide sustained chondrogenic induction is required (Zhao et al, 2020). PLGA µS were good drug carriers and capable of sustaining and localizing delivery of bioactive drugs to dictate surrounding cell behaviors (Asgari et al, 2020;Zhao et al, 2020). In the present study, the release profile of KGN-incorporated PCL/MECM hybrid scaffold exhibited an initial burst release in the early phase, followed by a slow constant release for over 28 days, which suggested that this drug delivery scaffold system can provide sustained chondrogenic environment for meniscus tissue regeneration (Figure 3I).…”

Implantation of Various Cell-Free Matrixes Does Not Contribute to the Restoration of Hyaline Cartilage within Full-Thickness Focal Defects

“…At the same time, the presence of invaded cells gives hope that a scaffold with growth factors being chondrogenic for these cells may work well. Along these lines, Y. Zhao [ 27 ] and Z. Jia [ 28 ] have recently shown that the combination of a scaffold consisting of cartilage extracellular matrix and microspheres of polylactide-glycolic acid with TGF-ß3 (transforming growth factor-beta 3) stimulated the new cartilage tissue formation in the almost entire injury site. The newly formed tissue contained round chondrocytes and showed higher levels of collagen type 2 and aggrecans [ 27 , 28 ].…”

“…Along these lines, Y. Zhao [ 27 ] and Z. Jia [ 28 ] have recently shown that the combination of a scaffold consisting of cartilage extracellular matrix and microspheres of polylactide-glycolic acid with TGF-ß3 (transforming growth factor-beta 3) stimulated the new cartilage tissue formation in the almost entire injury site. The newly formed tissue contained round chondrocytes and showed higher levels of collagen type 2 and aggrecans [ 27 , 28 ]. Thus, cell-free scaffolds optimization by adding cytokines and/or growth factors is a promising strategy for the future.…”

3D Printing for Bone-Cartilage Interface Regeneration

“…Moreover, Zhao et al (2020) prepared KGN-encapsulating PLGA microspheres using a solid-oil-water double solvent evaporation technique, complexed with CECM scaffolds containing TGF-β3, and demonstrated that the scaffold prolonged the activity of KGN and supported the adhesion, proliferation, and chondrogenic differentiation of BMSCs in vitro . Moreover, Zhao et al (2020) reported the successful integration of new cartilage at the defect site with surrounding tissues in a rabbit femoral condylar cartilage defect model. This study provided novel insights regarding the generation of scaffolds with kartogenin, however, no positive synergy was observed between kartogenin and TGF-β3 ( Zhao et al, 2020 ).…”