Hydrophilic polyurethanes as synthetic matrix to induce chondrogenic fate of stem cells.

摘要

Control of stem cell fate in tissue engineering application is important for effective and functional tissue regeneration. Extracellular matrix provides appropriate cues at nano-scale dimension to guide the cell fate. Polyurethanes (PUs) are segmental polymers with nanostructured phase morphology which can mimic the nano-scale characteristic features of native extracellular matrix. Thus, biodegradable polyurethanes can act as synthetic matrix to provide instructive signals to cells by inducing appropriate cell-matrix interactions. Recent studies have shown that segmental-polycaprolactone (PCL) based biphasic polyurethane matrices provides appropriate nano-cues to control the mesenchymal stem cells (MSCs) fate. These PCL based polyurethane matrices are hydrophobic in nature and, therefore are not suitable for regeneration of naturally hydrated tissues such as cartilage. Hydrophilic, polyethylene glycol (PEG) based polyurethane matrixes were fabricated with defined structure and composition to provide nano-cues with an emphasis to guide the MSCs into chondrogenic fate to regenerate cartilage. Effect of these matrices on MSC behavior and function was examined on two dimensional (2D) matrix and three dimensional (3D) systems and results show that human MSCs can sense the matrix signals which are derived from the nanostructured phases of polyurethanes. On 2D matrices, phase characteristics of hydrophilic polyurethanes modulated adhesion, proliferation, actin filament formation, focal adhesion points, circularity index (C.I.), and surface area (S.A) of stem cells. Based on the interactions of MSCs with 2D matrices, chondrogenic differentiation of MSCs into cartilage-like tissue was induced by polyurethane matrixes in 3D microenvironment. Also, MSCs grown in 3D system formed cartilage-like tissue without the need of chondrogenic medium. In conclusion, nano-cues provided by PEG based polyurethane matrices are sensed by the cell to guide their fate to form cartilage-like tissue regeneration.