In vivo assessment of grafted cortical neural progenitor cells and host response to functionalized self-assembling peptide hydrogels and the implications for tissue repair

Abstract

Tissue specific scaffolds formed from minimalist N-fluorenylmethyloxycarbonyl self-assembling peptides (Fmoc-SAPs) have emerged as promising biomaterials due to their ease of synthesis and capacity to self-assemble via simple, non-covalent interactions into complex nanofibrous hydrogels. However, concerns remain over their biocompatibility and cytotoxicity for in vivo applications. Here, we demonstrate that these Fmoc-SAPs are biocompatible in vivo and well suited as a delivery vehicle for cell transplantation. In order to determine the effect of tissue specific parameters, we designed three Fmoc-SAPs containing varying bioactive peptide sequences derived from extracellular matrix proteins, laminin and fibronectin. Fmoc-SAPs delivering cortical neural progenitor cells into the mouse brain display a limited foreign body response, effective functionalization and low cytotoxicity for at least 28 days. These results highlight the suitability of Fmoc-SAPs for improved neural tissue repair through the support of grafted cells and adjacent host parenchyma. Overall, we illustrate that Fmoc-SAPs are easily engineered materials for use as a tool in cell transplantation, where biocompatibility is key to promoting cell survival, enhancing the graft-host interface and attenuation of the inflammatory response for improved tissue repair outcomes.