Functional tissue-engineered microtissue derived from cartilage extracellular matrix for articular cartilage regeneration. (1st September 2018)

• Record Type: Journal Article
• Authors: Yin, Heyong; Wang, Yu; Sun, Xun; Cui, Ganghua; Sun, Zhen; Chen, Peng; Xu, Yichi; Yuan, Xueling; Meng, Haoye; Xu, Wenjing; Wang, Aiyuan; Guo, Quanyi; Lu, Shibi; Peng, Jiang
• Is Part Of: Acta biomaterialia. Volume 77(2018)
• Page Start: 127
• Page End: 141
• Publication Date: 2018-09-01
• Subjects: ACAN aggrecan -- ACs articular chondrocytes -- ASCs adipose-derived stem cells -- bFGF basic fibroblast growth factor -- BMP-6 bone morphogenetic protein 6 -- BMSCs bone marrow-derived mesenchymal stem cells -- BV/TV the ratio of bone volume to tissue volume -- CEDPs cartilage extracellular matrix-derived particles -- COL1A1 collagen, type I, alpha 1 -- COL2A1 collagen, type II, alpha 1 -- COL10A1 collagen, type X, alpha 1 -- ECM extracellular matrix -- FBS fetal bovine serum -- sGAG sulfated glycosaminoglycans -- GAPDH glyceraldehyde 3-phosphate dehydrogenase -- H&E hematoxylin and eosin -- IGF-1 insulin-like growth factor -- MG microgravity -- Micro-CT microcomputed tomography -- MRI magnetic resonance imaging -- MSCs mesenchymal stem cells -- PBS phosphate-buffered saline -- RCCS rotary cell culture system -- SDS sodium dodecyl sulfate -- SEM scanning electron microscopy -- SOX9 transcription factor SOX9 -- ST static -- Tb.Th trabecular bone thickness -- TGF transforming growth factor; Cartilage -- Regeneration -- Chondrocyte -- Stem cell -- Tissue engineering; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2018.07.031
• Languages: English
• ISSNs: 1742-7061

Abstract

Graphical abstract: Abstract: We developed a promising cell carrier prepared from articular cartilage slices, designated cartilage extracellular matrix (ECM)-derived particles (CEDPs), through processes involving physical pulverization, size screening, and chemical decellularization. Rabbit articular chondrocytes (ACs) or adipose-derived stem cells (ASCs) rapidly attached to the surface of the CEDPs and proliferated with high cell viability under microgravity (MG) condition in a rotary cell culture system (RCCS) or static condition. Gene profiling results demonstrated that ACs expanded on CEDPs exhibited significantly enhanced chondrogenic phenotypes compared with monolayer culture, and that ASCs differentiated into a chondrogenic phenotype without the use of exogenous growth factors. Moreover, MG culture conditions in a RCCS bioreactor were superior to static culture conditions in terms of maintaining the chondrogenic phenotype of ACs and inducing ACS chondrogenesis. With prolonged expansion, functional microtissue aggregates of AC- or ASC-laden CEDPs were formed. Further, AC- or ASC-based microtissues were directly implanted in vivo to repair articular osteochondral defects in a rabbit model. Histological results, biomechanical evaluations, and radiographic assessments indicated that AC- and ASC-based microtissues displayed equal levels of superior hyaline cartilage repair, whereas the other two treatment groups, in which osteochondral defects were treated with CEDPs alone or fibrin glue, exhibited primarily fibrous tissue repair. These findings provide an alternative method for cell culture and stem cell differentiation and a promising strategy for constructing tissue-engineered cartilage microtissues for cartilage regeneration. Statement of Significance: Despite the remarkable progress in cartilage tissue engineering, cartilage repair still remains elusive. In the present study, we developed a cell carrier, namely cartilage extracellular matrix-derived particles (CEDPs), for cell proliferation of articular chondrocytes (ACs) and adipose-derived stem cells (ASCs), which improved the maintenance of chondrogenic phenotype of ACs, and induced chondrogenesis of ASCs. Moreover, the functional microtissue aggregates of AC- or ASC-laden CEDPs induced equal levels of superior hyaline cartilage repair in a rabbit model. Therefore, our study demonstrated an alternative method for chondrocyte culture and stem cell differentiation, and a promising strategy for constructing tissue-engineered cartilage microtissues for in vivo articular cartilage repair and regeneration.