Annulus fibrosus (AF) injuries lead to substantial intervertebral disc deterioration which characterizes degenerative disc diseases. Repair of AF, however, remains challenging due to the tremendous heterogeneity of Annulus fibrosus tissue. Since the differentiation of stem cells significantly relies on the elasticity of substrate, a series of biodegradable poly(ether carbonate urethane)urea (PECUU) materials whose elasticity resembled that of native Annulus fibrosus tissue were synthesized in this study. When Annulus fibrosus-derived stem cells (AFSCs) were cultured on electrospun PECUU fibrous scaffolds, the gene expression and protein production of major matrix components, including collagen-I, collagen-II and aggrecan, and cell traction forces gradually changed with the elasticity of PECUU. Such substrate elasticity-dependent modulation of Annulus fibrosus-derived stem cells was similar to the gradual transition in the genetic, biochemical, and biomechanical characteristics of cells from inner to outer regions of native Annulus fibrosus tissue. This work has, for the first time, revealed that Annulus fibrosus-derived stem cells are able to present different gene expression patterns simply as a result of the elasticity of scaffold material. Findings from this study will help develop adequate materials for Annulus fibrosus regeneration.
Caihong Zhu, Jun Li, Chen Liu, Pinghui Zhou, Huilin Yang, Bin Li.
Department of Orthopaedics, The First Affiliated Hospital, Orthopaedic Institute, Soochow University, 188 Shizi St, Suzhou, Jiangsu 215006, China.
These authors contributed equally to this study. Email: [email protected]
Annulus fibrosus (AF) injuries commonly lead to substantial deterioration of the intervertebral disc (IVD). While tissue engineering has recently evolved into a promising approach for AF regeneration, it remains challenging due to the cellular, biochemical, and mechanical heterogeneity of AF tissue. In this study, we explored the use of AF-derived stem cells (AFSCs) to achieve diversified differentiation of cells for AF tissue engineering. Since the differentiation of stem cells relies significantly on the elasticity of the substrate, we synthesized a series of biodegradable poly(ether carbonate urethane)urea (PECUU) materials whose elasticity approximated that of native AF tissue. When AFSCs were cultured on electrospun PECUU fibrous scaffolds, the gene expression of collagen-I in the cells increased with the elasticity of scaffold material, whereas the expression of collagen-II and aggrecan genes showed an opposite trend. At the protein level, the content of collagen-I gradually increased with substrate elasticity, while collagen-II and GAG contents decreased. In addition, the cell traction forces (CTFs) of AFSCs gradually decreased with scaffold elasticity. Such substrate elasticity-dependent changes of AFSCs were similar to the gradual transition in the genetic, biochemical, and biomechanical characteristics of cells from inner to outer regions of native AF tissue. Together, findings from this study indicate that AFSCs, depending on the substrate elasticity, have strong tendencies to differentiate into various types of AF-like cells, thereby providing a solid foundation for the tissue engineering applications of AFSCs.
Copyright © 2016. Published by Elsevier B.V.Go To Acta Biomater