Intra-articular delivery of synovium-resident mesenchymal stem cells via BMP-7-loaded fibrous PLGA scaffolds for cartilage repair

Hee Jung Kim, Min Ah Han, Ji Young Shin, Jeong Hwa Jeon, Seung Jin Lee, Mi Yun Yoon, Han Jun Kim, Eun Ji Choi, Sun Hee Do, Victor C. Yang, Huining He, Young Il Yang

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Delivery of synovium-resident mesenchymal stem cells (synMSCs) to cartilage defect site might provide a novel therapeutic modality for treatment of articular cartilage diseases. However, low isolation efficiency of synMSCs limits their therapeutic application. Niche-preserving non-enzymatic isolation of synMSCs was firstly attempted by employing micro-organ culture system based on recapitulating tissue-specific homeostasis ex vivo. The isolated synMSCs retained superior long-term growth competency, proliferation and chondrogenic potential to bone marrow-derived MSCs (BMSCs). It was noted that synMSCs demonstrated 9-fold increase in cartilaginous micro-tissue formation and 13-fold increase in sulfated proteoglycans deposition compared to BMSCs. For delivery of synMSCs, fibrous PLGA scaffolds were specifically designed for full-thickness osteochondral defects in rabbits. The scaffolds provided effective micro-environment for growth and host-integration of synMSCs. Combined delivery of synMSCs with bone morphogenetic proteins-7 (BMP-7) was designed to achieve synergistic therapeutic efficacy. BMP-7-loaded PLGA nanoparticles electrosprayed onto the scaffolds released BMP-7 over 2 weeks to conform with its aimed role in stimulating early stage endochondral ossification. Scaffold-supported combined administration of synMSCs with BMP-7 resulted in high proteoglycan and collagen type II induction and thick hyaline cartilage formation. Intra-articular co-delivery of synMSCs with BMP-7 via fibrous PLGA scaffolds may be a promising therapeutic modality for articular cartilage repair.

Original languageEnglish
Pages (from-to)169-180
Number of pages12
JournalJournal of Controlled Release
Volume302
DOIs
StatePublished - 28 May 2019

Keywords

  • Articular cartilage repair
  • Bone morphogenetic protein-7
  • Combined delivery
  • PLGA fibrous scaffold
  • Synovium-resident mesenchymal stem cells

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