Peptide- and protein-mediated assembly of heparinized hydrogels

Abstract

Polymeric hydrogels have demonstrated significant promise in biomedical applications such as drug delivery and tissue engineering. A continued direction in hydrogel development includes the engineering of the biological responsiveness of these materials, via the inclusion of cell-binding domains and enzyme-sensitive domains. Ligand-receptor interactions offer additional opportunities in the design of responsive hydrogels, and strategies employing protein-polysaccharide interactions as a target may have unique relevance to materials intended to mimic the extracellular matrix (ECM). Accordingly, we have developed approaches for producing hydrogels via noncovalent interactions between heparin and heparin-binding peptides/proteins, and have demonstrated that such matrices are capable of both passive and receptor-mediated growth factor delivery. Further modification of these materials via the integration of these noncovalent strategies with chemical crosslinking methods will expand the range of their potential use and is under exploration. The combination of these approaches offers broad opportunities for the production of responsive matrices for biomedical applications.

Designing hydrogels for controlled drug delivery

“…As an example of a system exploiting charge interactions, elastin-like polypeptides have been cross-linked via electrostatic interactions between their cationic lysine residues and anionic organophosphorus cross-linkers 34 . Non-covalent interactions between heparin and heparin-binding peptides and proteins can be used to form hydrogels for growth factor delivery 35,36 . Another in situ -gelling hydrogel was formed with a polyelectrolyte complex, which showed a sustained release of proteins (for example, insulin and Avidin) over two weeks 37 .…”

Injectable polymeric hydrogels for the delivery of therapeutic agents: A review

“…Using a rather similar scheme, self-assembled DNA hydrogels were prepared via the base-pairing interaction of complementary DNA strands [138][139][140]. In other promising approaches, biomolecules-responsive bioconjugated hydrogels were obtained through ligandreceptor interaction between heparin and growth factors [141], glucose and concanavalin A [142], or antigenantibody binding between rabbit IgG and goat anti-rabbit IgG [143,144]. Lastly, metal-ligand coordination between iron(II) and bipyridine [145,146], nickel(II) and terpyridine [147], or iron(III) and catechol [148] were exploited to produce metallo-hydrogels.…”

Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration

“…Polymer-based materials have been widely employed for various biomedical applications including vocal fold tissue engineering due to their flexibility in tuning materials properties such as porosity, crosslinking chemistry and density, microstructures and mechanical strength, as well as coupling multiple biological moieties to the scaffolds. [56,63,128–130]…”

“…[166,178–182] In the initial attempts to engineer such hydrogels, the Kiick laboratories have adopted 12 repeats of a 15-amino-acid repetitive sequence with the putative motif GGRPSDSYGAPGGGN as a structural domain to impart mechanical properties, with additional incorporation of the cell-binding ligand RGDSPG,[183] the matrix metalloproteinase (MMP)-sensitive sequence GPQGIWGQ [184,185] and the heparin-binding domain KAAKRPKAAKDKQTK to induce matrix-cell interaction. [63,186,187] The resilin-like polypeptides (RLPs) are easily crosslinked to yield tunable elastic shear and Young’s moduli of values comparable to those measured for vocal fold tissues (500–5000Pa at low frequency (1–10Hz), 200–2000 at higher frequency (30–150Hz) and 10–50kPa at low strain (<15%), respectively). [18,188–190] Hydrated, crosslinked films of RLPs also show excellent extensibility (up to 300%), efficient recovery, negligible stress relaxation and hysteresis, as well as high resilience (97%) characterized via standard stress-strain cyclic tensile testing, suggesting their flexibility and utility to efficiently transmit mechanical forces.…”