Bioactive porous peg-peptide composite hydrogels with tunable mechanical properties

Abstract

Mimicking the instructive cues of native extracellular matrix (ECM) is fundamental to understand and control the processes regulating cell function and cell fate. Extensive research on the structure and biological complexity of ECM has shown that three types of critical information from the ECM have influence on cellular behaviour: (1) biophysical properties (elasticity, stiffness), (2) biochemical properties (bioactive peptide epitopes of ECM molecules), and (3) nanoarchitecture (nanofibrillar structure, porosity) of ECM. Recent efforts have therefore focused on the construction of ECM mimetic materials to modulate tissue specific cell functions. Advances in biomaterial platforms include artificial ECM mimics of peptide conjugated synthetic polymer hydrogels presenting bioactive ligands produced with covalent chemistry. These materials have already found application in tissue engineering, however, these biomaterial platforms represent oversimplified mimics of cellular microenvironment and lack the complexity and multifunctional aspects of native ECM. In this work, we developed a novel polyethylene glycol (PEG)-peptide nanofiber composite hydrogel system with independently tunable biochemical, mechanical and physical cues that does not require any chemical modification of polymer backbone to create synthetic ECM analogues. This approach allows noninteracting modification of multifactorial niche properties (i.e. bioactive ligands, stiffness, porosity), since no covalent conjugation method was used to modify PEG monomers for the incorporation of bioactivity and porosity. Combining the self-assembled peptide nanofibers with crosslinked polymer network simply by facile mixing followed by photo-polymerization resulted in the formation of porous hydrogel systems. Resulting porous network can be functionalized with desired bioactive signalling epitopes by simply altering the amino acid sequence of peptide amphiphile molecules. In addition, the mechanical properties of the composite system can be precisely controlled by changing the PEG concentration. Ultimately, multifunctional PEG-peptide composite scaffolds reported in this work, can fill a critical gap in the available biomaterials as versatile synthetic mimics of ECM with independently tunable properties. Such a system could provide a useful tool allowing the investigation of how complex niche cues interplay to influence cellular behaviour and tissue formation both in 2D and 3D platforms.