Jonathan J. Wilker

A review on tough and sticky hydrogels

In this review, we survey recent literature (2009–2013) on hydrogels that are mechanically tough and adhesive. The impact of published work and trends in the field are examined. We focus on design concepts, new materials, structures related to mechanical performance and adhesion properties. Besides hydrogels made of individual polymers, concepts developed to toughen hydrogels include interpenetrating and double networks, slide ring polymer gels, topological hydrogels, ionically cross-linked copolymer gels, nanocomposite polymer hydrogels, self-assembled microcomposite hydrogels, and combinations thereof. Hydrogels that are adhesive in addition to tough are also discussed. Adhesive properties, especially wet adhesion of hydrogels, are rare but needed for a variety of general technologies. Some of the most promising industrial applications are found in the areas of sensor and actuator technology, microfluidics, drug delivery and biomedical devices. The most recent accomplishments and creative approaches to making tough and sticky hydrogels are highlighted. This review concludes with perspectives for future directions, challenges and opportunities in a continuously changing world.

Visible absorption spectra of metal–catecholate and metal–tironate complexes

Interactions between metals and catechol (1,2-dihydroxybenzene) or other ortho-dihydroxy moieties are being found in an increasing number of biological systems with functions ranging from metal ion internalization to biomaterial synthesis. Although metal-catecholate interactions have been studied in the past, we present the first systematic study of an array of these compounds, all prepared under identical conditions. We report the ultraviolet-visible absorption (UV-vis) spectra for catecholate and tironate complexes of the first row transition elements. Generation and identification of these species were accomplished by preparing aqueous solutions with varied ligand:metal ratios and subsequently titrating with base (NaOH). Controlled ligand deprotonation and metal binding resulted in sequential formation of complexes with one, two, and sometimes three catecholate or tironate ligands bound to a metal ion. We prepared the mono-, bis- and tris-catecholates and -tironates of Fe(3+), V(3+), V(4+)and Mn(3+), the mono- and bis-catecholates and -tironates of Cu(2+), Co(2+), Ni(2+), Zn(2+), Cr(2+) and Mn(2+), and several Ti(4+) and Cr(3+) species. The UV-vis spectra of each complex are described, some of which have not been reported previously. These data can now be applied to characterization of biological metal-catecholate systems.

Marine bioinorganic materials: mussels pumping iron.

The oceans are filled with an amazing variety of biological materials including the glues and cements of mussels, barnacles, tube worms, algae, and starfish. Recent studies on mussel adhesive are providing increasing evidence for a unique mechanism of material generation involving iron-induced protein oxidation and cross-linking chemistry. Insights are also being gathered on many of the other marine creatures producing adhesives. Beyond understanding biology, this growing knowledge is inspiring application development. New classes of biomimetic polymers are poised to provide the next generation of surgical adhesives and orthopedic cements.

The Iron-Fortified Adhesive System of Marine Mussels

Look to the seas and you will find a variety of fascinating materials residing within, from shells to reefs to adhesives. Barnacles, giant clams, limpets, tube worms, star fish, sea cucumbers, and kelp are examples of the many organisms that produce adhesives and cements to aid survival. These species can affix themselves to rocks and thereby build communities that deter predators, aid reproduction, and decrease buffeting of the turbulent intertidal zone. The adhesive system used by blue mussels has become the focus of much attention for ongoing biomaterials characterization (Figure 1). This attachment system is called a “byssus” or “beard”, owing to the threads fanning out from between shells (Figure 1). Adhesive plaques terminate each thread and make contact with the surface. Both the threads and the plaques are predominantly protein, with high levels of the unusual 3,4-dihydroxyphenylalanine (DOPA) residue present (Figure 1). An amazing story is now emerging in which iron has been found to bind these DOPA proteins for two separate, but related, purposes: to improve the mechanical performance of the threads and to bring about formation of the adhesive plaques. Mussel threads are an extensible and hard material comprised of two distinct regions: an inner core and a thin outer coating. Similarities to human hair are both visual and biochemical. Crystalline protein domains of collagen make up the thread core, and elastin and fibroin domains are also present. DOPA proteins form the thin (2–5 mm) outer cuticle and make this coating approximately 5–10 times harder and stiffer than the core. The first indication that metals may be influencing materials properties of the threads was the observation that treatment with chelators (e.g., ethylenediaminetetraacetic acid) resulted in softening and changes to the stress–strain behavior. Native threads are able to recover from stress. Upon chelation treatment, this “self-healing” property was lost, but it was recovered when metal ions were returned, which showed that any relevant metal–protein interactions are reversible. Examination of the cuticle

Biomaterials: Redox and adhesion on the rocks

Man-made adhesives cannot match the ability of a marine mussel to affix itself to a wet rock. New insights help to describe the protein-surface bonding central to this feat of biological materials engineering.

Bulk adhesive strength of recombinant hybrid mussel adhesive protein

Mussel adhesive proteins (MAPs) have received increased attention as potential biomedical and environmental friendly adhesives. However, practical application of MAPs has been severely limited by uneconomical extraction and unsuccessful genetic production. Developing new adhesives requires access to large quantities of material and demonstrations of bulk mechanical properties. Previously, the authors designed fp-151, a fusion protein comprised of six MAP type 1 (fp-1) decapeptide repeats at each MAP type 5 (fp-5) terminus and successfully expressed it in Escherichia coli. This recombinant hybrid protein exhibited high-level expression, a simple purification and high biocompatibility as well as strong adhesive ability on a micro-scale. In the present work, investigations on the bulk adhesive properties of semi-purified (∼90% purity) fusion fp-151 were performed in air. The unmodified recombinant fp-151, as expressed, contains tyrosine residues and showed significant shear-adhesive forces (∼0.33 MPa). Adhesion strength increased (∼0.45 MPa) after enzymatic oxidation of tyrosine residues to l-3,4-dihydroxyphenylalanine (DOPA) groups. Addition of cross-linkers such as iron(III), manganese(III) and periodate (IO4 −) generally enhanced adhesion, although too much addition decreased adhesion. Among the three cross-linking reagents examined, the non-metallic oxidant periodate showed the highest shear-adhesive forces (∼0.86 MPa). In addition, it was found that adhesive strengths could be increased by adding weights to the samples. The highest adhesion strength found was that of DOPA-containing fp-151 cross-linked with periodate and having weights applied to the samples (∼1.06 MPa). Taken together, the first bulk-scale adhesive force measurements are presented for an expressed recombinant hybrid mussel adhesive protein.

Synthesis of peptides containing DOPA (3,4-dihydroxyphenylalanine)

Abstract Proteins from coral reefs structures, eggshells, and marine mollusk adhesives all contain the amino acid 3,4-dihydroxyphenylalanine (DOPA). The insoluble nature of these materials has hampered characterization and turned our efforts toward work with small peptide mimics. In this paper, we present the syntheses of various DOPA derivatives: Boc-DOPA, Fmoc-DOPA, DOPA(TBDMS)2, DOPA(TBDPS)2, Boc-DOPA(TBDPS)2, Fmoc-DOPA(TBDMS)2, and Fmoc-DOPA(TBDPS)2 (where Boc=tert-butyloxycarbonyl, Fmoc=9-fluorenylmethyloxycarbonyl, TBDMS=tert-butyldimethylsilyl, and TBDPS=tert-butyldiphenylsilyl). These DOPA compounds were used to prepare peptides of various sequences. The synthetic procedure described provides an efficient route to DOPA-containing peptides in which sidechain deprotection and cleavage from resin can be accomplished in one step.

Molecular weight effects upon the adhesive bonding of a mussel mimetic polymer.

Characterization of marine biological adhesives are teaching us how nature makes materials and providing new ideas for synthetic systems. One of the most widely studied adhering animals is the marine mussel. This mollusk bonds to wet rocks by producing an adhesive from cross-linked proteins. Several laboratories are now making synthetic mimics of mussel adhesive proteins, with 3,4-dihydroxyphenylalanine (DOPA) or similar molecules pendant from polymer chains. In select cases, appreciable bulk bonding results, with strengths as high as commercial glues. Polymer molecular weight is amongst several parameters that need to be examined in order to both understand biomimetic adhesion as well as to maximize performance. Experiments presented here explore how the bulk adhesion of a mussel mimetic polymer varies as a function of molecular weight. Systematic structure-function studies were carried out both with and without the presence of an oxidative cross-linker. Without cross-linking, higher molecular weights generally afforded higher adhesion. When a [N(C4H9)4](IO4) cross-linker was added, adhesion peaked at molecular weights of ~50,000-65,000 g/mol. These data help to illustrate how changes to the balance of cohesion versus adhesion influence bulk bonding. Mussel adhesive plaques achieve this balance by incorporating several proteins with molecular weights ranging from 6000 to 110,000 g/mol. To mimic these varied proteins we made a blend of polymers containing a range of molecular weights. Interestingly, this blend adhered more strongly than any of the individual polymers when cross-linked with [N(C4H9)4](IO4). These results are helping us to both understand the origins of biological materials as well as design high performance polymers.

Absorption spectroscopy and binding constants for first-row transition metal complexes of a DOPA-containing peptide.

A diverse array of biological systems incorporate 3,4-dihydroxyphenlyalanine (DOPA) into proteins and small molecules for cross-linking and material generation. Marine worm eggshells, sea squirt wound plugs, and marine mussel adhesives may all be formed by combining DOPA-containing molecules with high levels of metals. In order to provide model systems for characterizing these biomaterials, we carried out a study on metal binding to a DOPA-containing peptide. Ultraviolet-visible absorption spectra are presented for the AdopaTP peptide binding to Fe3+, V3+, VO2+, Mn3+, Ti4+, Cu2+, Co2+, and Ni2+ in mono, bis, and where applicable, tris coordination modes. Association constants were determined for selected metal ions binding to the peptide. In general, the spectroscopic and binding properties of this DOPA-containing peptide were found to be similar to those of catechol.

A Method for Measuring the Adhesion Strength of Marine Mussels

Marine mussels produce a byssal adhesive assembly for attachment to surfaces in the marine environment. The byssus is characterized by an array of adhesive plaques, each attached to threads that are anchored inside the animal. Here we describe a rapid method for determining detachment force, area, and overall adhesion of mussel plaques. Adhesion forces for mussels attached to glass, aluminum, acrylic, polyvinyl chloride (PVC), and Silastic® T2 are reported. This method may aid in the development of new adhesive materials and antifouling surfaces.