Layered Double Hydroxide and Polypeptide Thermogel Nanocomposite System for Chondrogenic Differentiation of Stem Cells

Abstract

Stem cell therapy for damaged cartilage suffers from low rates of retention, survival, and differentiation into chondrocytes at the target site. To solve these problems, here we propose a two-dimensional/three-dimensional (2D/3D) nanocomposite system. As a new two-dimensional (2D) material, hexagonal layered double hydroxides (LDHs) with a uniform lateral length of 2-3 μm were prepared by a hydrothermal process. Then, tonsil-derived mesenchymal stem cells (TMSCs), arginylglycylaspartic acid-coated LDHs, and kartogenin (KGN) were incorporated into the gel through the thermal-energy-driven gelation of the system. The cells exhibited a tendency to aggregate in the nanocomposite system. In particular, chondrogenic biomarkers of type II collagen and transcription factor SOX 9 significantly increased at both the mRNA and protein levels in the nanocomposite system, compared to the pure thermogel systems. The inorganic 2D materials increased the rigidity of the matrix, slowed down the release of a soluble factor (KGN), and improved cell-material interactions in the gel. The current 2D/3D nanocomposite system of bioactive LDH/thermogel can be a new platform material overcoming drawbacks of hydrogel-based 3D cell culture systems and is eventually expected to be applied as an injectable stem cell therapy.

Layered Double Hydroxides Are Promising Nanomaterials for Tissue Bioengineering Application

“…Although the interaction of cells with biomaterials is a crucial step to the success of bioengineering protocol, little advance was made reporting the molecular panorama supporting cell adaptation to biomaterials. On this sense, Lee et al have elegantly proposed an LDH‐based nanocomposite as a new platform material carrying and delivering injectable stem cell in therapy, mainly because these cells exhibit a tendency to adhere onto the nanocomposite and further triggering chondrogenic signaling …”

Layered Double Hydroxides: A Toolbox for Chemistry and Biology

“…In their experiments, they prepared Poly(3-Hydroxybutyric acid)-Poly (N-vinylpyrrolidone) fibers loaded with MgAl LDHs and coated over the hydroxyapatite pellets for the realization of bone grafts; the resulting systems showed good compatibility towards MG63 human osteosarcoma 3AB-OS cancer stem cell lines. LDH nanocomposites with arginylglycylaspartic acid and kartogenin were incorporated into a gel together with tonsil-derived mesenchymal stem cells [214]. Interestingly, the cells were observed to aggregate in the nanocomposite system.…”

Application of Tonsil-Derived Mesenchymal Stem Cells in Tissue Regeneration: Concise Review

“…Upon culturing TMSCs in chondrogenic media, the expression of the chondrogenic markers aggrecan (AGN) and collagen type II (COL2) as well as the accumulation of sulfated glycosaminoglycan‐rich matrix visualized by Alcian blue staining increased, yet COL2 expression was lower in the chondrogenically differentiated TMSCs compared with those of chondrogenically differentiated BM‐MSCs. Later, other groups tested 2‐dimensional (2D)/3D hybrid systems to enhance the chondrogenic differentiation efficiency of TMSCs . These studies revealed significant increases in the chondrogenic markers COL2 and SOX9, demonstrating the improved biofunctionality of chondrogenically differentiated TMSCs by the 2D/3D hybrid cell culture system.…”