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

Abstract

Meniscus tissue engineering (MTE) aims to fabricate ideal scaffolds to stimulate the microenvironment for recreating the damaged meniscal tissue. Indeed, favorable mechanical properties, suitable biocompatibility, and inherent chondrogenic capability are crucial in MTE. In this study, we present a composite scaffold by 3D printing a poly(ε-caprolactone) (PCL) scaffold as backbone, followed by injection with the meniscus extracellular matrix (MECM), and modification with kartogenin (KGN)-loaded poly(lactic-co-glycolic) acid (PLGA) microsphere (μS), which serves as a drug delivery system. Therefore, we propose a plan to improve meniscus regeneration via KGN released from the 3D porous PCL/MECM scaffold. The final results showed that the hydrophilicity and bioactivity of the resulting PCL/MECM scaffold were remarkably enhanced. In vitro synovium-derived mesenchymal stem cells (SMSCs) experiments suggested that introducing MECM components helped cell adhesion and proliferation and maintained promising ability to induce cell migration. Moreover, KGN-incorporating PLGA microspheres, which were loaded on scaffolds, showed a prolonged release profile and improved the chondrogenic differentiation of SMSCs during the 14-day culture. Particularly, the PCL/MECM-KGN μS seeded by SMSCs showed the highest secretion of total collagen and aggrecan. More importantly, the synergistic effect of the MECM and sustained release of KGN can endow the PCL/MECM-KGN μS scaffolds with not only excellent cell affinity and cell vitality preservation but also chondrogenic activity. Thus, the PCL/MECM-KGN μS scaffolds are expected to have good application prospects in the field of MTE.

Tetrahedral framework nucleic acids promote the biological functions and related mechanism of synovium-derived mesenchymal stem cells and show improved articular cartilage regeneration activity in situ

“…The study was approved by the Ethical Committee of PLA. Isolation and culture of SMSCs were performed according to a previous method [ 33 , 34 ]. In general, articular synovial tissue was obtained from the knee joints of male New Zealand rabbits (1 month old, 500–800 g) on a sterile bench.…”

Mesenchymal Stem Cells From Different Sources in Meniscus Repair and Regeneration

“…A study by Tarafder et al (2018) reported that the controlled applications of CTGF and TGF-β3 can induce seamless healing of avascular meniscus tears by inducing the recruitment and step-wise differentiation of SMSCs. Additionally, chemical and physical conditions have also been further investigated, with promising results in PCL electrospinning technology, magnesium ions, 3D printing-based biomimetic, and composite tissue-engineered meniscus scaffold ( Shimomura et al, 2019 ; Zhang et al, 2019 ; Li et al, 2020 ; Li et al, 2021 ). To ensure clinical efficacy, the proper transport of SMSCs from the processing facility to the clinic is important.…”

Meniscus repair: up-to-date advances in stem cell-based therapy

“…In another study, Li et al . [ 109 ] fabricated an ingenious scaffold as a drug and stem cell delivery system, which composed of 3D-printed PCL, meniscus extracellular matrix (MECM), and KGN-loaded poly(lactic-co-glycolic) acid (PLGA) microsphere (Fig. 4 ).…”