Repair of osteochondral defects with in vitro engineered cartilage based on autologous bone marrow stromal cells in a swine model

Aijuan He,Yilin Cao,Wei Liu,Yu Liu,Yi Liu,Zhiyong Zhang,Xusong Luo,Xiaoyun Wang,Wenjie Zhang,Lina Liu,Guangdong Zhou,Fangjun Liu

doi:10.1038/srep40489

Aijuan He, Yilin Cao + Show 10 more

Open Access

https://doi.org/10.1038/srep40489

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Abstract

Functional reconstruction of large osteochondral defects is always a major challenge in articular surgery. Some studies have reported the feasibility of repairing articular osteochondral defects using bone marrow stromal cells (BMSCs) and biodegradable scaffolds. However, no significant breakthroughs have been achieved in clinical translation due to the instability of in vivo cartilage regeneration based on direct cell-scaffold construct implantation. To overcome the disadvantages of direct cell-scaffold construct implantation, the current study proposed an in vitro cartilage regeneration strategy, providing relatively mature cartilage-like tissue with superior mechanical properties. Our strategy involved in vitro cartilage engineering, repair of osteochondral defects, and evaluation of in vivo repair efficacy. The results demonstrated that BMSC engineered cartilage in vitro (BEC-vitro) presented a time-depended maturation process. The implantation of BEC-vitro alone could successfully realize tissue-specific repair of osteochondral defects with both cartilage and subchondral bone. Furthermore, the maturity level of BEC-vitro had significant influence on the repaired results. These results indicated that in vitro cartilage regeneration using BMSCs is a promising strategy for functional reconstruction of osteochondral defect, thus promoting the clinical translation of cartilage regeneration techniques incorporating BMSCs.

Highlights

Success rate of osteochondral defect repair is not satisfactory[20], which obviously limits further clinical translation of cell-scaffold constructs
What is the cartilage formation process for BMSC in vitro engineered cartilage (BEC-vitro)? Second, can implantation of BEC-vitro alone realize tissue-specific repair of articular osteochondral defects with both cartilage and subchondral bone in a large animal model? Third, does the maturity level of BEC-vitro affect the efficacy of repair? And whether prolonged in vitro pre-culture has influence on in situ integration of the implant? All these issues directly restrict the clinical translation of BEC-vitro and, require thorough investigation
BMSCs on polyglycolic acid/polylactic acid (PGA/PLA) scaffold was first evaluated by scanning electron microscopy (SEM) during the early stage of in vitro culture

Summary

Introduction

Success rate of osteochondral defect repair is not satisfactory[20], which obviously limits further clinical translation of cell-scaffold constructs. Primary advantages include convenient handling for surgeons (similar to autologous cartilage transplantation), reduced cell leakage[15], mild inflammatory reaction because of minimal or no remnant scaffold[16,17], convenient quality control before implantation, superior mechanical properties, and more reliable cartilage regeneration after implantation (cartilage had formed before implantation and, was less influenced by the traumatic environment)[18,19]. Despite these advantages, some important issues are still unknown.

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