Photofunctionalization of Alginate Hydrogels to Promote Adhesion and Proliferation of Human Mesenchymal Stem Cells

Abstract

Photocrosslinkable biomaterials are promising for biomedical applications, as they can be injected in a minimally invasive manner, crosslinked in situ to form hydrogels with cells and/or bioactive factors, and engineered to provide instructive signals to transplanted and host cells. Our group has previously reported on biodegradable, photocrosslinkable alginate (ALG) hydrogels with controlled cell adhesivity for tissue engineering. The polymer backbone of this methacrylated ALG was covalently modified with cell adhesion ligands containing the RGD sequence to enhance the proliferation and differentiation response of encapsulated cells. However, this approach permits limited control over the spatial presentation of these ligands within the three-dimensional hydrogel structure. Here we present a system that easily allows for spatial control of cell adhesion ligands within photocrosslinked ALG hydrogels. A cell adhesive peptide composed of the specific amino acid sequence Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) was covalently modified with acrylate moieties. The acrylated peptide was then covalently incorporated into bulk hydrogels by adding it to methacrylated ALG solutions with a photoinitiator, and then photocrosslinking under long-wave ultraviolet light. The hydrogels were characterized with respect to their swelling and degradation profiles, and the effects of the acrylated peptide on human mesenchymal stem cell (hMSC) viability, adhesion, spreading, and proliferation were examined in vitro. hMSC adhesion and spreading on and proliferation in this biomaterial system could be regulated by varying the concentration of cell adhesion ligand. This new biomaterial system may be a useful platform for tissue engineering, drug delivery, and stem cell transplantation with spatial control of cell adhesivity.