Hydrogels are common biomaterials that find their application in tissue engineering, and can be used for tissue regeneration. The introduction of a biomaterial into the tissue causes specific cellular outcomes as the cells can not only sense the presence of bioactive ligands but also the stiffness and mechanical properties of the material. The mechanotransduction-based pathways influence the adhesion, migration and differentiation of cells Therefore, one of the benefits of using hydrogel-based scaffolds is that their biomechanical and biochemical properties are highly tunable and can be optimized to mimic a tissue. This means that those hydrogel-based scaffolds have to mimic the extracellular environment, or extracellular matrix (ECM) of the tissues that the cells are normally embedded in. In today’s blog post I will try to present an interesting polymer composite made out of Poly(ethylene glycol) (PEG), and self-assembled peptide amphiphile (PA).
In this design, PEG provides for the mechanical base of the scaffold. The benefits of using this hydrogel are that it is water-soluble, highly biocompatible, and nonimmunogenic. However, its downside is that PEG as such does not allow for cell adhesion and therefore must be functionalized with ECM-derived bioactive proteins. The approach allows for including peptides without affecting the crosslinking of PEG through photoactivation.
PA on the other hand can self-assemble into cylindrical, fibrous networks under physiological pH an temperature. Upon incorporation of bioactive proteins, PA hydrogels become a highly biocompatible, fibrous materials which allow for cell adhesion.
The hydrogel composite presented in the paper I reviewed, consisted of PA with incorporated bioactive peptides, namely RGD, DGEA (from collagen I), and PEG-dimethacrylate (PEGDMA) in different volumetric ratios. That is, the final concentrations of PEGDMA were in the range 4-15% (w/v) and 0.1% (w/v) of the photoinitiator, which allowed for obtaining gels of different Young’s modulus (0.1-8 kPa). The self-assembling PA proteins included a hydrophobic fatty acid and hydrophilic peptide parts which allowed for the self-assembly of PA within the composite, and were further conjugated to the bioactive peptides. The final concentration of PA in the composite was 1.5%, and was enough to allow for cell adhesion, spreading and proliferation. Overall, the design is such that PA-peptide and PEG are mixed under physiological conditions to allow for formation of nanofibers within the solution first, and only then it is subjected to photoactivation and the methacrylate groups of PEGDMA form a polymeric network. As a result, the composite is lamellar, mesoporous (pores in the nanometer range) and resembles the ECM structure. The gels also show isotropic behavior due to the equal dispersion of PA in PEGDMA. The bioactive peptides on PA are available for cells and do not alter the PEG crosslinking. Additionally, this means that the same structure should be obtained regardless of the peptide incorporated into PA, and the structural properties should not be altered.
Why am I trying to draw your attention to ECM-mimetic composites? Throughout this semester I have been trying to find biomaterial-based approaches for the treatment of fibrosis in different tissues and organs, however I have found that the field still offers many opportunities for new advancements. This ECM biomimetic allows for both altering the biochemical composition as well as biomechanical properties of the gels. Both 3D and 2D gels can be constructed with use of this design. This and similar designs could be used in research, which would allow for better understanding of fibrotic diseases and ultimately designing new, hopefully successful treatments.
References:
Goktas, M., Cinar, G., Orujalipoor, I., Ide, S., Tekinay, A. B., & Guler, M. O. (2015). Self-assembled peptide amphiphile nanofibers and PEG composite hydrogels as tunable ECM mimetic microenvironment. Biomacromolecules, 16(4), 1247-1258.