The Application And Studies Of Tissue Engineered Cartilage Based On In Vitro Construction

Functional repair of large size cartilage defects remains a great challenge in clinical treatment due to limited regenerative ability of cartilage tissue.Tissue engineering technology has been proposed as a promising cartilage regeneration strategy,but some important issues are always obstacles to clinical translation of this strategy.such as the limited cells source,the unstable in vitro cartilage regeneration approach,the in vivo immunological rejection of the biological materials,and the unknown biologic behaviors of engineered cartilage derived chondrocytes.Cell source is an important obstacle for clinical translation of engineered cartilage.Therefore,to investigate a suitable cell source for clinical application is the key to solve this problem.The current study was to explore the biologic behaviors of different chondrocytes,and the results confirmed that: auricular and nasoseptal cartilage could obtain more chondrocytes compared with costal cartilage based on the same weight of samples;no significant differences were observed in cartilage regeneration ability among auricular,nasoseptal,and costal chondrocytes;cartilage type analysis revealed that the regenerated cartilage tended to retain their original cartilage types and structures after in vivo implantation.Besides,we also confirmed that microtia chondrocytes could provide a chondrogenic niche and promote BMSCs transform into chondrocyte-like cell,and a human-ear-shaped cartilage was finally constructed with co-transplantation of microtia chondrocytes and BMSCs in a nude mouse.These results provided a reasonable guide for the selection of seeding cells in clinical application.The in vivo immunological rejection of the polymer scaffold is another important obstacle for clinical translation of engineered cartilage.A stable in vitro cartilage regeneration approach is the key to solve this problem.Although we have established the in vitro cartilage construction approach based on animal cells,up to now,engineering large size cartilage with special shape based on human cells have not achieved significant breakthrough.To address this issue,the current study was to explore the feasibility of biomechanical stimulus for improving the mechanical property of engineered cartilage,the feasibility of introduction 3D printing technique for engineering special shape cartilage,and the cell biologic behavior of chondrocyte derived from engineered cartilage.We found that early stage of in vitro biomechanical stimulus was benefit for improving the mechanical property of engineered cartilage;it was possible to engineering special shape cartilage with the assistance of 3D printing technique based on human cells;chondrocytes derived from engineered cartilage remained high proliferation rate and robust cartilage regeneration potential after long time in vitro culture.These results established the foundation for the clinical application of engineered cartilage.Clinical translation of tissue engineered cartilage was the final goal of these researches.Based on the above investigated results,we have started a series of clinical trials,such as human auricular chondrocytes engineered cartilage in vitro for nasal reconstruction and meibomian reconstruction,and BMSCs engineered cartilage or subchondral bone for articular defect or osteochondral defect repair.From these clinical trials,we have preliminarily confirmed that these in vitro engineered cartilages could regenerate mature cartilage tissue after implanted into human subcutaneous;those engineered nasal-shape cartilage could repair nasal cartilage defect and maintain the natural nose shape;the meibomian-shape cartilage could repair the meibomian and reconstruction a natural meibomian after the excision of eyelid divided nevus;and BMSCs engineered cartilage or subchondral bone in vitro could repair articular osteochondral defect,reconstruct the joint function,and greatly release the articular symptoms.All these works provide powerful evidence for clinical translation of in vitro engineered human cartilage.