Biological buffer-mediated self-assembly of modular nucleo-peptide hydrogels for tissue engineering applications

Hydrogel scaffolds are at the forefront of tissue engineering research due to several distinct characteristics, namely highly hydrated, diffusive environments and physical and structural characteristics that mimic the extracellular matrix. These supports are derived from a variety of base materials, including a range of synthetic polymers and biologically derived mimics. Self-assembling peptides have recently emerged as promising hydrogel-forming species offering advantages across that spectrum, such as inherent biocompatibility and highly tunable and functional characteristics—both due to the nature and characteristics of amino acids. Research has so far been limited by certain factors, however; in particular, requisite hydrophobic protecting groups which encourage noncovalent interactions yet demonstrate cytotoxic effects, unpredictable self-assembly after modifications to the native chain, and harsh environmental self-assembly triggers and conditions. We have developed a gelation methodology that combines sodium salts of nucleobases and peptides into one hydrogel-forming species that associates in solutions of biological buffers and dissolved ions. Further, mechanical properties are tunable post-gelation through added divalent cations that lead to order of magnitude increases in elastic character, thereby making robust, consistently reproducible constructs and improving workability in the laboratory. These factors combined also create a physiological environment conducive to tissue-engineering applications. Further, we have incorporated functionality into our constructs by taking advantage of the nature of self-assembly: the nucleo-peptide foundation aggregates and interacts noncovalently with functional peptides and bioactive molecules, integrating them into the hydrogel nanostructure. We utilize this quality to improve biostability of the scaffold and encourage cell attachment and long-term viability, along with making progress towards influencing growth, proliferation, and genetic expression. Our modular scaffolds are therefore highly tunable and influence cell behavior directly and purposefully in situ. This novel approach of adopting a biological focus first furthers the potential of short peptides and their derivatives in regenerative medicine.Biomedical Engineerin