Exploiting the supramolecular self-assembly of β-sheet forming peptides to design tailored 3D cell niches

摘要

Introduction: In the last two decades, significant efforts have been made to develop soft materials exploiting the self-assembly of short peptides for biomedical applications. β-sheet forming peptides have been shown to allow the design of highly stable hydrogels with potential application is a range of fields. In particular, they offer a flexible platform for the design of 3D cell niches. Figure 1: Schematic representation of the self-assembly process of β-sheet forming peptides Materials and Methods: We have developed a platform for the design of hydrogels with tailored properties and functionalities exploiting the self-assembly of short (4-10 amino acids) β-sheet forming peptides. The design of these peptides is based on the alternation of hydrophilic and hydrophobic residues. These novel materials have been characterized using a variety of techniques including small angle scattering and rheology. Results & Discussion: The self-assembly process of these peptides was investigated and is schematically described in Figure 1. By altering the peptide primary structure, the formulation and the processing conditions the properties of these scaffolds (e.g.: modulus and functionality) can be easily controlled. We were able to design injectable, as well as sprayable, hydrogels that can be used for 3D cell culture as well as in-vivo cell delivery. Figure 2: G' vs time showing the shear thinning properties of the hydrogels and therefore their injectbility. We have used these novel materials for the culture of a variety of cells including chondrocytes, osteoblasts, fibroblasts, embryonic as well as mesemchyme stem cells. One highly attractive feature is the ease of functionalisation of these materials which makes them an ideal platform for the design of 3D cell niches. In addition these materials are biodegradable and show low immugeniciry allowing their use in-vivo. Figure 3: Effect of RGD fuctionalisation on the adehsion of mouse friboblast showing that hydrogel can be easily functionalised to suit cell needs. Conclusions: We have developed a platform for the design of 3D scaffolds whose properties can be tailored to accommodate different cells' needs. Our results dearly demonstrate that our peptides offer great promise for the design of specific cell niches due to their low immunogenicity and the ability we have to control and tailor their properties.