Design of a Peptide-Based Electronegative Hydrogel for the Direct Encapsulation, 3D Culturing, in Vivo Syringe-Based Delivery, and Long-Term Tissue Engraftment of Cells

Abstract

Soft materials that facilitate the three-dimensional (3D) encapsulation, proliferation, and facile local delivery of cells to targeted tissues will aid cell-based therapies, especially those that depend on the local engraftment of implanted cells. Herein, we develop a negatively charged fibrillar hydrogel based on the de novo-designed self-assembling peptide AcVES3-RGDV. Cells are easily encapsulated during the triggered self-assembly of the peptide leading to gel formation. Self-assembly is induced by adjusting the ionic strength and/or temperature of the solution, while avoiding large changes in pH. The AcVES3-RGDV gel allows cell-material attachment enabling both two-dimensional and 3D cell culture of adherent cells. Gel-cell constructs display shear-thin/recovery rheological properties enabling their syringe-based delivery. In vivo cellular fluorescence as well as tissue resection experiments show that the gel supports the long-term engraftment of cells delivered subcutaneously into mice.