A water-borne adhesive modeled after the sandcastle glue of P. californica

Abstract

Polyacrylate glue protein analogs of the glue secreted by Phragmatopoma californica, a marine polycheate, were synthesized with phosphate, primary amine, and catechol sidechains with molar ratios similar to the natural glue proteins. Aqueous mixtures of the mimetic polyelectrolytes condensed into liquid complex coacervates around neutral pH. Wet cortical bone specimens bonded with the coacervates, oxidatively crosslinked through catechol sidechains, had bond strengths nearly 40% of the strength of a commercial cyanoacrylate. The unique material properties of complex coacervates may be ideal for development of clinically useful adhesives and other biomaterials.

Figure 1

Structure and UV-vis characterization of mimetic copolymers: a) The Pc3 analog, 1, contained 88.4 mol-% phosphate, 9.7 mol-% dopamide, and 0.1 mol-% FITC sidechains. The Pc1 analog, 2, contained 8.1 mol-% amine sidechains. The balance was acrylamide subunits in both cases. b) A single peak at 280 nm characteristic of the catechol form of 3,4-dihydroxyphenol was present in the spectrum of 1. Following oxidation with NaIO₄ a peak at 395 nm corresponding to the quinone form appeared confirming the expected redox behavior of the 3,4-dihydroxyphenol-containing polymer.

Figure 2

pH-dependent complex coacervation of mixed polyelectrolytes. a) At low pH, a 50 mg · mL⁻¹ mixture of 1 and 2 having equal quantities of amine and phosphate sidechains formed stable colloidal PECs. As the pH increased the polymers condensed into a dense liquid complex coacervate phase. At pH = 10 the copolymers went into solution and oxidatively crosslinked into a clear hydrogel. b) The net charge of the copolymer sidechains as a function of pH calculated from the copolymer sidechain densities. c) The diameter of the PECs (circles) increased nearly three-fold over the pH range 2–4. Above pH = 4 the complexes flocculate and their size could not be measured. The zeta potential (squares) was zero near pH = 3.6 in agreement with the calculated net charge.

Figure 3

Liquid character of complex coacervate. The solution of 1 and 2 contained equal quantities of amine and phosphate sidechains, pH = 7.4.

Figure 4

Phase diagram of polyelectrolytes and divalent cations. The amine to phosphate sidechain and phosphate sidechain to divalent cation ratios were varied at a fixed pH = 8.2. The state of the solutions represented in a gray scale. The mass (mg) of the coacervate phase is indicated in the dark grey squares. The compositions indicated with an asterisk were used to test bond strength.

Figure 5

Bond strength, shear modulus, and dimensional stability of coacervate bonded bones. a) Bond strength at failure increased ≈50% and the stiffness doubled as the divalent cation ratio went from 0 to 0.4 relative to phosphate sidechains. Specimens wet bonded with a commercial cyanoacrylate adhesive were used as a reference (n = 6 for all conditions). b) Bonds of adhered bone specimens fully submerged in PBS for four months (pH = 7.2) did not swell appreciably.

Figure 6

Model of pH dependent coacervate structure and adhesive mechanisms. a) The polyphosphate (black) with low charge density paired with the polyamine (dark grey) form nm-scale complexes. The complexes have a net positive charge. b) Extended high charge density polyphosphates form a network connected by more compact lower charge density polyamines and when present divalent cations (light grey symbols). The net charge on the copolymers is negative. c) Oxidation of 3,4-dihydroxyphenol (D) by O₂ or an added oxidant initiates crosslinking between the quinone (Q) and primary amine sidechains. The coacervate can adhere to the hydroxyapatite surface through electrostatic interactions, 3,4-dihydroxyphenol sidechains, and quinone-mediated covalent coupling to matrix proteins.