Designing a Bioactive Scaffold from Coassembled Collagen-laminin Short Peptide Hydrogels for Controlling Cell Behaviour

Synthetic bioactive hydrogels have been widely recognized as key elements of emerging strategies for tissue engineering. The complex hierarchical structure and chemical composition of the natural ECM inspires us to design multi-component ECM mimics that have potential applications in biomedicine. Taking inspiration from natural proteins, we hypothesized that designing a multi-component synthetic matrix based on short ECM derived peptides will be highly beneficial for providing a functional scaffold, which still remains a challenge in the field of biomaterials. For the proof of concept, we designed a composite hydrogel scaffold inspired by the two essential components of native ECM, collagen and laminin, which play diverse roles in supporting cell growth. To the best of our knowledge, we have designed the shortest collagen inspired peptide sequence Nap-FFGSO, which has propensity to self-assemble in the presence of short laminin mimetic peptides. Interestingly, only 10% w/w of laminin peptides was sufficient to provide nucleation and growth of the nanostructures in the collagen inspired peptide and induces further self-assembly to create higher order structures. Such a nucleation and growth mechanism can trigger gelation in the collagen inspired peptides, which otherwise failed to form a gel under physiological conditions. We could achieve similar complexity in the designed matrix through utilization of simple non-covalent interactions, rather than covalent synthetic methodologies to create a dual functional matrix from the non-gelator collagen inspired peptide. The nanofibrous morphology generated through co-assembly can essentially mimic the structure and function of natural ECM, which enables the scaffold to communicate with cells through biochemical signals and promote cell growth, adhesion, proliferation and migration. We envisage that this structural mimicry of a native collagen fibrillar network using such a short peptide sequence can lead to new opportunities for developing next generation functional materials. The strategy of supramolecular assembly using multiple components could develop a plethora of viable biomaterials under physiological conditions.