Injectable Hydrogels Prepared Using Novel Synthetic Short Peptides with Defined Structure and Gelatin as Scaffolds to Support Cell and Tissue Growth

Animal-derived basement-membrane matrices such as Geltrex are used to grow cells and tissues. Particularly, they are commonly applied to support tumor growth in animals for cancer research. However, a material derived from an animal source has an undefined composition, and may thus have unavoidable batch-to-batch variation in properties. To overcome these issues, we designed a series of synthetic short peptides to form hydrogels in combination with gelatin to promote cell adhesion and growth. The peptides have sequences of (X1Y1×2Y2)2, where X1 and X2 are hydrophobic residues, while YI and Y2 are hydrophilic residues. The peptides spontaneously folded and self-assembled into a β-sheet secondary structure upon contact with salts, and then aggregated to form hydrophilic networks of hydrogels. Hybrid hydrogels formed by mixing the peptide IEVEIRVK (IVK8) with gelatin are injectable and enzymatically degradable. The hybrid hydrogels at optimal compositions supported SW480 and HepG2 tumor spheroid growth in vitro as effectively as Geltrex. More importantly, the peptide/gelatin hydrogels supported tumor growth in a SW480 human colorectal adenocarcinoma xenograft mouse model. Altogether, our results illustrated that the synthetic peptide/gelatin hybrid hydrogel is a promising scaffold that can be used to support cell and tissue growth both in vitro and in vivo.