Peptide Programmed Hydrogels as Safe Sanctuary Microenvironments for Cell Transplantation

Abstract

Cell transplantation is one of the most promising strategies for the minimally invasive treatment of a raft of injuries and diseases. However, a standing challenge to its efficacy is poor cell survival due to a lack of mechanical protection during administration and an unsupportive milieu thereafter. In response, a shear-injectable nanoscaffold vector is engineered considering the three equal requirements of protection, support, and survival. Here, the programmed peptide assembly of tissue-specific epitopes presents a safe sanctuary microenvironment for the transplantation of cells. For the first time, a mechanistic understanding of the multifactorial role of the nanoscaffold in promoting cell survival is presented, where initial cell survival is dependent on the fluid mechanic process of droplet formation rather than on shear rate. However, provided is the first report of the most critical component of a transplantation vector, distinguishing feigned biological support from mechanical properties from true ongoing biological support post transplantation. This is achieved via the presentation of amino acid constituents that significantly improve the efficacy of the vector compared to a biocompatible, yet inert analogue. Together, the peptide-programmed hydrogels enable fundamental rules for the engineering of advanced treatment strategies with wide reaching implications for tissue repair and biofabrication.