From the hard ‘knock’ of bone to the soft ‘plop’ of gray matter, tissues cover an enormous spectrum of hardnesses – and they would be well to do so, for the stresses they must answer to are similarly diverse. Even stem cells are savvy enough to change their own hardness to match their peers, probing the environment to decide on their course of differentiation – and this property is well-known and well-abused in regenerative medicine, as any method that allows directed differentiation is coveted by biologists. Bioengineering methods based on mechanical induction, however, do have a catch: While stiffness-tunable polymers can readily assume whatever surface hardness is required of them, they do not display the all-too-vital bioactive signals that call out for cells to adhere on them, and some, such as PEG, may in fact actively repel biological matter like a no-stick pan. But recent research by laboratories of Professors Mustafa Özgür Güler and Ayşe Begüm Tekinay suggests that a generous helping of self-assembling peptide amphiphiles provides a solution for this particular problem.
The diversity and ease of synthesis associated with peptide amphiphile molecules have made them ubiquitous in biology. Their popularity is further helped by the fact that these molecules assemble into well-organized structures – and the team’s work now demonstrates that the same property also allows the peptide networks to integrate into a polymer matrix. The initial concentration of the polymer component, poly(ethylene) glycol (PEG), is a key element for modulating the stiffness of the whole assembly: A concentration of 4% results in a soft gel with a stiffness comparable to brain tissue, while 8% PEG creates the formation of an intermediate matrix mechanically similar to internal organs such as the kidney or the live, and a concentration of 12% results in the formation of a still harder material. And while PEG handles the mechanical properties, the peptide sequence provides the biological information necessary to recruit cells: the authors show that peptide amphiphile molecules bearing the integrin recognition sequences RGD and DGEA enhance the spreading areas and trigger the osteogenic activity of Saos-2 cells.
Although prior reports have incorporated similar designs, the PEG/PA material is advantageous in that it requires no direct modification of the polymer, as the self-assembled PA networks non-covalently assemble onto the structure following the crosslinking of the PEG matrix. The authors hope that further modification of their composite polymer/PA nanofiber hydrogels may allow development of artificial structures closely resembling the native extracellular matrix in both mechanical and biological aspects, noting that such materials would ‘fill a critical gap in the available biomaterials as versatile synthetic mimics of ECM with independently tunable properties’.
Their work has been published in the journal Biomacromolecules and can be accessed at the following address: