The Interplay Between Cell Adhesion Cues and Curvature of Cell Adherent Alginate Microgels in Multipotent Stem Cell Culture

Abstract

Cell-adherent microcarriers are increasingly used to expand multipotent stem cells on a large scale for therapeutic applications. However, the role of the microcarrier properties and geometry on the phenotypic activities of multipotent cells has not been well studied. This study presents a significant interplay of the number of cell adhesion sites and the curvature of the microcarrier in regulating cell growth and differentiation by culturing mesenchymal stem cells on alginate microgels chemically linked with oligopeptides containing the Arg-Gly-Asp (RGD) sequence. Interestingly, the cell growth rate and osteogenic differentiation level were increased with the RGD peptide density. At a given RGD peptide density, the cell growth rate was inversely related to the microgel diameter, whereas the osteogenic differentiation level was minimally influenced. The dependency of the cell growth rate on the microgel diameter was related to changes in shear stresses acting on cells according to simulation. Overall, this study identifies material variables key to regulating cellular activities on microcarriers, and these findings will be useful to designing a broad array of bioactive microcarriers.

RGD‐peptide modified alginate by a chemoenzymatic strategy for tissue engineering applications

“…Other modifications of the encapsulation system, not investigated in the current study, may influence both cell viability and function. Such modifications may include further modulating the mechanics and/or molecular composition of the alginate microbeads, combining RGD peptide with other functional peptides, as well as testing other concentrations of both encapsulated OECs and alginates. Furthermore, strategies for inducing covalent crosslinks by peptides in the gel network allowing for the encapsulated cells to modify their microenvironment are shown to be of importance for the morphology and differentiation of mesenchymal stem cells .…”

Self‐Assembling Peptides as Cell‐Interactive Scaffolds

“…[53] Microcarriers such as microgels to culture adherent cells in suspension using a bioreactor offer a better alternative for scale-up. [54] In addition, microgels that are able to encapsulate cells offer added advantages such as the ability to engineer tissues with multiple chemical environments. [55] Microgels fabricated from self-assembling peptides have been constructed using various methods, including microfluidics, [55,56] microemulsion, [57] and electrospray.…”

Engineered protein coatings to improve the osseointegration of dental and orthopaedic implants

“…The RGD ligand is well known to promote proliferation of MSCs; thus, this enhancement in DNA is thought to reflect a faster rate of proliferation. [107, 108] The higher DNA content on scrambled ELP-coated titanium relative to uncoated titanium at time points between 10 and 28 days is presumably due to the nonspecific adsorption of serum proteins. These data are consistent with previous reports that the number of hMSCs on ELP coated-titanium between days 7 and 22 were statistically similar on coatings with and without the RGD ligand.…”