Hydrogel biomaterials: a smart future?

Abstract

Hydrogels were the first biomaterials developed for human use. The state-of-the-art and potential for the future are discussed. Recently, new designs have produced mechanically strong synthetic hydrogels. Protein-based hydrogels and hybrid hydrogels containing protein domains present a novel advance; such biomaterials may self-assemble from block or graft copolymers containing biorecognition domains. One of the domains, the coiled coil, ubiquitously found in nature, has been used as an example to demonstrate the developments in the design of smart hydrogels. The application potential of synthetic, protein based, DNA based, and hybrid hydrogels bodes well for the future of this class of biomaterials.

Figure 1

Synthetic hydrogels with excellent mechanical properties. (A) Topological sliding hydrogel. α-Cyclodextrin moieties threaded on PEG chains, end-capped with a bulky group, are crosslinked by trichlorotriazine producing double ring crosslinks freely movable along the PRG chains (adapted from ref. [3]); (B) Double network hydrogels composed from two hydrophilic networks, one highly crosslinked, the other loosely crosslinked [4]; and (C) Nanocomposite (clay filled) hydrogels synthesized by radical polymerization of N-isopropylacrylamide in the presence of uniformly dispersed clay sheets (adapted from ref. [5]).

Figure 2

Coiled-coil protein domains. (A) Cartoon depicting the interaction of two heptads. The hydrophobic core is formed by the interactions of amino acid residues in positions a and d. (B) Helical wheel representation of two-stranded, antiparallel α-helical coiled-coils formed by the dimerization of CCE and CCK. The view is shown looking down the superhelical axis from the N-terminus of CCE and from the C-terminus of the CCK. CC denotes the coiled-coil peptides. E and K denote peptides in which most of the e and g positions are occupied by either glutamic acid or lysine, respectively. (C) Schematic illustration of the parallel or antiparallel orientation of two coiled-coil strands. (D) Primary structure of CCE and CCK. The sequences are written in the one-letter amino acid code. Positions a and d of the heptad repeats are underlined and form the hydrophobic core of the coiled-coil. N and C denote the amino and carboxy ends of the α-helix, respectively. Cartoons are from ocw.mit.edu/NR/rdonlyres/Biology.

Figure 3

Temperature dependence of the secondary structures of the protein polymers. CD signal (ellipticity) at 222 nm as a function of temperature (modified from ref. [12]). In A₂, K replaced V in the a position of the 4^th heptad, and three additional K residues replaced S in the c positions of the 3^rd, 4^th, and 5^th heptads (indicated by bold italics).

Figure 4

(A) Self-assembly of HPMA graft copolymers, CCK-P and CCE-P, containing oppositely charged peptide grafts (P is the HPMA copolymer backbone; see Figure 2 for structure of CCE and CCK). Aqueous solutions of CCE-P or CCK-P did not form gels. In contrast, gel-like materials were formed from equimolar mixtures of CCE-P/CCK-P at low concentrations. (B) pH dependence of the secondary structure of CCE, CCK, and equimolar mixture CCE/CCK expressed as the content of α-helix. (C) Microrgeology of 1% w/v solutions of CCE-P, CCK-P, and equimolar mixture of CCE-P/CCK-P. Mean square displacement of tracking particles as a function of time. (D) CD spectra of the equimolar mixture CCK-P/CCE-P before (full tilted squares) and after (empty triangles) denaturation by guanidine hydrochloride at 25 °C at a 20 µM peptide concentration and after removal of guanidine hydrochloride by dialysis (empty squares). Adapted from [10].