Integrin specificity as a novel strategy for enhancing transplanted stem cell survival and tissue repair in vivo

Hydrogels are an attractive class of materials for cell encapsulation due to properties that mimic the extracellular matrix such as high water content and simple diffusion of waste and nutrients, minimal adverse host reactions, relatively mild reaction conditions, and opportunity for minimally invasive delivery as injectable carriers. Due to their defined chemical compositions, synthetic polymers can be prepared in reproducible and predictable fashions and can be modified to tune material properties such as degradation rate, mechanical properties, and shape/configuration large advantages over natural polymers that display heterogeneity and structural complexity that renders modifications difficult. The lack of cell adhesion sites on most synthetic polymers yields the opportunity for engineering specificity into the material by incorporating cell adhesive sites or growth factors, independently of substrate mechanical properties. In this aim, we have engineered an integrin-specific stem cell microenvironment using biomimetic adhesive ligands using a novel hydrogel chemistry without the use of cytotoxic photoinitiators and UV light. We have shown that we can control material properties of the matrix independently of ligand peptide and tune material properties such as storage modulus by varying hydrogel parameters. Ligand-functionalized hydrogels exhibited binding specificity to target integrins, and we observed differences in cell morphology in 3-D due to ligand activity while maintaining high cell viability. In addition, integrinspecific hydrogels supported for FAK activation and upregulated osteoblastic