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

Hao Li; Zhiyao Liao; Zhen Yang; Cangjian Gao; Liwei Fu; Pinxue Li; Tianyuan Zhao; Fuyang Cao; Wei Chen; Zhiguo Yuan; Xiang Sui; Shuyun Liu; Quanyi Guo

doi:10.3389/fbioe.2021.662381

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

Front Bioeng Biotechnol. 2021 Apr 30:9:662381. doi: 10.3389/fbioe.2021.662381. eCollection 2021.

Authors

Hao Li^{1

2}, Zhiyao Liao^{1

2}, Zhen Yang^{1

2}, Cangjian Gao^{1

2}, Liwei Fu^{1

2}, Pinxue Li^{1

2}, Tianyuan Zhao^{1

2}, Fuyang Cao^{1

3}, Wei Chen^{1

2}, Zhiguo Yuan⁴, Xiang Sui¹, Shuyun Liu¹, Quanyi Guo^{1

2}

Affiliations

¹ Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, Beijing, China.
² School of Medicine, Nankai University, Tianjin, China.
³ Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁴ Department of Bone and Joint Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

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.

Keywords: 3D printing; PCL; kartogenin; meniscus extracellular matrix; meniscus tissue engineering.