HYDROGELS FROM SOFT CONTACT LENSES AND IMPLANTS TO SELF-ASSEMBLED NANOMATERIALS

Abstract

Hydrogels were the first biomaterials designed for clinical use. Their discovery and applications as soft contact lenses and implants are presented. This early hydrogel research served as a foundation for the expansion of biomedical polymers research into new directions: design of stimuli sensitive hydrogels that abruptly change their properties upon application of an external stimulus (pH, temperature, solvent, electrical field, biorecognition) and hydrogels as carriers for the delivery of drugs, peptides, and proteins. Finally, pathways to self-assembly of block and graft copolymers into hydrogels of precise 3D structures are introduced.

Figure 1

A) First polymerization apparatus for spin casting of soft contact lenses built from a construction set of O. Wichterle’s grandson (www.21stoleti.cz/view.php?cisloclanku=2005021823); B) contact lens (www.soft-contacts.biz); C) Structure of hydrogels used in early soft contact lenses – copolymer of HEMA with EDMA.

Figure 2

Hydrogel implants. Clinical use of hydrogels (copolymers of HEMA with EDMA) in rhinoplasty. (a) patient before surgery; (b) patient after surgery.

Figure 3

Structures of early hydrogels.

Figure 4

Stimuli sensitive hydrogels. First detailed study of the relationship between the structure of hydrogels and their pH-dependent properties. pH sensitivity of 2-hydroxyethyl methacrylate copolymer-based hydrogels was achieved by introducing ionogenic groups into the hydrogel structure. The permeability of NaCl through a hydrogel membrane containing basic units of N,N-dimethylaminoethylmethacrylate (1) increased in the acidic region, whereas the permeability of membranes containing methacrylic acid units (2) increased in the alkaline region. Permeability through an ampholytic membrane (3), containing approximately the same quantities of methacrylic acid and N,N-dimethylaminoethylmethacrylate, passed through a minimum in the isoelectric point and increased as the pH diverged from the isoelectric point in either direction. Adapted from reference .

Figure 5

Mechanically improved hydrogels. Schematic structure of a topological sliding hydrogel. α-Cyclodextrin moieties threaded on PEG chains (end-capped with a bulky group) were crosslinked by trichlorotriazine producing double (and probably triple) ring crosslinks freely movable along the PEG chains. The sliding of crosslinks results in a decrease of inhomogeneities of the network and in regulation of the tension with concomitant enhancement of mechanical properties. Adapted from references –.

Figure 6

Traditional hydrogel synthesis. A) Crosslinking copolymerization; B) Crosslinking of polymer precursors with a low-molecular-weight crosslinking agent; C) Polymer-polymer reaction of two polymer precursors.

Figure 7

The impact of the distance between the vinyl groups of a crosslinking agent on the crosslinking efficacy is related to the probability of ring formation by alternating intermolecular-intramolecular chain propagation.

Figure 8

Hydrogel synthesis based on click chemistry and PEG-based building blocks.

Figure 9

Peptide motifs used in the design of hybrid hydrogels: Left panel: Coiled-coils; Right panel:β-sheets.

Figure 10

Self-assembly of genetically engineered ABA and CBC triblock copolymers into hybrid hydrogels. Minor manipulation of the primary structure of coiled-coil forming blocks provides a tool to modify temperature responsiveness of the 3D construct. Four amino acid residues of block A were replaced with lysine to produce block C.

Figure 11

Self-assembly of graft copolymers into hybrid hydrogels mediated by antiparallel heterodimer coiled-coil formation. Two distinct pentaheptad peptides (CCE and CCK) were designed to create a dimerization motif and serve as physical crosslinkers. Equimolar mixtures of the graft copolymers, CCE-P/CCK-P (P is the HPMA copolymer backbone), self-assemble into hydrogels in PBS (phosphate buffer) solution at neutral pH at low concentrations. A) Structure of copolymers and schematic of hydrogel formation through antiparallel heterodimeric coiled-coil association; B) CD spectra (in PBS; 100 μM of peptide) of CCE-P, CCK-P, and their equimolar mixture CCE-P/CCK-P; C) Comparison of gelation behavior among individual HPMA copolymer conjugates, CCE-P and CCK-P, and their equimolar mixture by microrheology; D) Normalized intensity autocorrelation functions for solutions of equimolar mixture of CCE-P and CCK-P (10 mg/mL) at time intervals indicated.

Figure 12

Hydrogels containing a triple mutant of adenylate kinase, AKtm (C77S, A55C, V169C), as a crosslinker are able to translate the enzyme conformation change upon binding a substrate into mechanical motion. A) Ribbon diagram of the structure of adenylate kinase (AKe) in two conformational states: open state (a); and closed state (b). B) HPMA-based hydrogels crosslinked with AKtm and dithiothreitol (DTT) and the macroscopic motion of hydrogels triggered by substrate recognition. The deswelling ratios of gel containing variable amounts of AKtm as crosslinker (0–100%). C) Three cycles of deswelling of hydrogel crosslinked with 100% of AKtm. Adapted from reference .