Development of three-dimensional articular cartilage construct using silica nano-patterned substrate

Abstract

Current strategies for cartilage cell therapy are mostly based on the use of autologous chondrocytes. However, these cells have limitations of a small number of cells available and of low chondrogenic ability, respectively. Many studies now suggest that fetal stem cells are more plastic than adult stem cells and can therefore more efficiently differentiate into target tissues. This study introduces, efficiency chondrogenic differentiation of fetal cartilage-derived progenitor cells (FCPCs) to adult cells can be achieved using a three-dimensional (3D) spheroid culture method based on silica nanopatterning techniques. In evaluating the issue of silica nano-particle size (Diameter of 300, 750, 1200 nm), each particle size was coated into the well of a 6-well tissue culture plate. FCPCs (2 x 10 5 cells/well in 6-well plate) were seeded in each well with chondrogenic medium. In this study, the 300 nm substrate that formed multi-spheroids and the 1200 nm substrate that showed spreading were due to the cell-cell adhesion force(via N-cadherin) and cell-substrate(via Integrin) force, the 750 nm substrate that formed the mass-aggregation can be interpreted as the result of cell monolayer formation through cell-substrate force followed by cell-cell contact force contraction. We conclude that our 3D spheroid culture system contributes to an optimization for efficient differentiation of FCPC, offers insight into the mechanism of efficient differentiation of engineered 3D culture system, and has promise for wide applications in regeneration medicine and drug discovery fields.

3D Spheroid Cultures of Stem Cells and Exosome Applications for Cartilage Repair

“…Despite the fact that controlling cell shape and positioning is a promising approach for cartilage repair, functional cell types and biomaterials are lacking [ 39 ]. Several studies to date have demonstrated that stem cells or progenitor cells derived from human fetal tissue are a promising cell source for cell therapy and tissue engineering [ 40 ]. Because of its high potential for biocompatibility compared to single cells, 3D culture technology has been steadily researched since the 1990s and has recently evolved into 3D spheroids.…”

3D-Cultured Adipose-Derived Stem Cell Spheres Using Calcium-Alginate Scaffolds for Osteoarthritis Treatment in a Mono-Iodoacetate-Induced Rat Model

“…ADSC spheroids have been suggested to improve cell biological properties, including increasing cell viability and proliferative capacity, stabilizing morphology, and improving metabolic functions, compared to 2D cultures [ 40 ]. In addition, it has been reported that 3D cultures can enhance differentiation markers and anti-inflammatory cytokine gene expression and stimulate ECM secretion [ 14 ]. In this study, the walking performance of 3D hADSC-treated MIA-induced OA rats were significantly improved compared to that of rats administered 2D-cultured hADSCs ( Figure 4 ).…”

“…Nevertheless, self-repair of articular cartilage (AC) is difficult because of its low regenerative capacity caused by the lack of blood supply, low cellularity, and a limited number of progenitor cells. Moreover, autograft cartilage cells also have limitations, such as the small number of cells available and low chondrogenic ability [ 14 ]. Stem cell treatment is another approach for the treatment of knee OA.…”

Autonomous spheroid formation by culture plate compartmentation

“…Alteration of adhesion molecule expression levels or switching to different types was shown during phases of development (e.g. NCAM) [36] and during differentiation in monolayer/3D culture [37,38]. Furthermore, the importance of cellular adhesion molecules, for interaction with substrate/extracellular matrix (ECM) and force distribution, has been presented (e.g.…”