Temperature responsive polyelectrolyte complexes: Bio-inspired wet-adhesives

Ilse Adriënne van Hees

Research output: Thesisinternal PhD, WU


For wound closure, adhesives provide many advantages over the use of sutures. However, adhesives are not yet common practice in internal medicine, due to limited adhesive properties in wet conditions, Chapter 1. In this thesis, we developed bio-inspired temperature responsive polyelectrolytes that can be applied as underwater adhesive, and may serve as biomedical adhesive as well.

A thorough understanding of natural underwater adhesives is needed for bio-mimicry and, therefore, we reviewed the adhesion mechanisms by sandcastle worms and mussels, Chapter 2. Sandcastle worms are marine organisms that build protective shells from minerals found in their surroundings, which are stuck together by adhesive proteins. Before secretion, these proteins are stored in granules in which anionic and cationic macromolecules are combined. Upon combining oppositely charged macromolecules, complex coacervation occurs, which explains the fluidic, yet concentrated, character of the packaged proteins. Mussels adhere through byssal threads and the two proteins closest to the surface are rich in the amino acid L-3,4-dihydroxyphenylalanine (DOPA). Therefore, DOPA is believed to be an adhesion promotor through a versatility of chemical interactions. Moreover, oxidation of DOPA can lead to covalent bonding, which can be used to solidify adhesives. Accordingly, DOPA is often used in the development of underwater adhesives.

In literature, several examples can be found of adhesives based on electrostatic interactions, which are composed of either recombinant proteins or synthetic polymers. From those articles, we extracted common features important for optimizing adhesive properties, Chapter 2. First, complexation between oppositely charged molecules improves adhesion, because significantly weaker adhesion is obtained when only one of the charged molecules is used. Moreover, multiple charged groups per molecule seem to result in materials with more powerful adhesive properties, than molecules that carry just one unit of charge. Furthermore, the adhesive strength of charged materials is improved upon the addition of catechol groups, such as DOPA, and even further enhanced by oxidation of DOPA after application to the surface. Finally, the inclusion of metal ions for metal coordination, or a second covalent network were also shown to increase the adhesive strength of complex coacervate based materials.

The adhesive proteins of sandcastle worms contain large amounts of oppositely charged and hydrophobic amino acids, and only limited amounts of DOPA. Therefore, we investigated adhesives based on electrostatic and hydrophobic interactions. The electrostatic interactions originate from oppositely charged polyelectrolytes (polyions) that form fluidic complex coacervates which enable easy application and a large adhesive interface. Solidification of the adhesive is achieved by introducing a thermo-responsive polymer with a lower critical solution temperature (LCST). In aqueous solution, this polymer is soluble at low temperatures, but becomes insoluble upon exceeding the LCST, because hydrophobic interactions become more dominant. As a result, temperature responsive polyelectrolyte complexes gel upon temperature increase.

The temperature responsive polyelectrolytes were prepared by reversible addition fragmentation chain-transfer (RAFT) polymerization, Chapter 3. Poly(N-isopropylacrylamide)-b-poly(acrylic acid)-b-poly(N-isopropylacrylamide) (PNIPAM-b-PAA-b-PNIPAM) was prepared by deprotection of PNIPAM-b-poly(tert-butyl acrylate)-b-PNIPAM, through a novel deprotection method to obtain complete removal of the tert-butyl groups, yielding anionic AA only. Two polymers with either 20 or 80 mole% NIPAM and a Mw/Mn of ~1.6 were prepared successfully. Moreover, we investigated the synthesis of the cationic PNIPAM-b-poly(dimethylaminoethyl methacrylate)- b-PNIPAM (PNIPAM-b-PDMAEMA-b-PNIPAM). The chain transfer agent and cationic PDMAEMA precursor were successfully synthesized and purified. However, it remained unclear whether extension with temperature responsive NIPAM succeeded. As a result, further investigations are required and we proceeded with commercially available polyactions.

Micelles are formed by mixing PNIPAM-b-PAA-b-PNIPAM and PNIPAM-b-PDMAEMA, with low PNIPAM contents, in aqueous solutions with various NaCl concentrations, Chapter 4. At low salt, the anionic PAA and cationic PDMAEMA form a complex and become insoluble, while PNIPAM has a temperature dependent solubility. Consequently, complex coacervate core micelles (C3M) with a PNIPAM corona were formed at low temperatures, while the polymers aggregate above the LCST. At high NaCl concentrations, however, the polyelectrolytes are soluble at room temperature because complexation is prevented by salt. Moreover, PNIPAM is salted out and therefore insoluble at any investigated temperature. Accordingly, a PNIPAM core micelle with a polyelectrolyte corona is formed at low temperatures. Upon heating, complex coacervation reoccurs and the polymers aggregate.

Temperature responsive polyelectrolyte complexes (TERPOC) are prepared in Chapter 5, by mixing PNIPAM-b-PAA-b-PNIPAM and PDMAEMA at various polymer and NaCl concentrations. At low temperatures, concentrated solutions with C3Ms were obtained, whereas heating caused gelation. The resulting TERPOCs are strong, turbid, but somewhat brittle gels because of the high PNIPAM content. Upon gelation, the sample volume is preserved, which is likely caused by the polyelectrolytes, e.g. by forming water pockets. Moreover, charge neutralization by PDMAEMA is required to retrieve strong gels. Furthermore, the strength of the TERPOC and the gelation temperature, Tgel, can be adjusted by altering the salt or polymer concentration. Consequently, the toughest TERPOC was obtained at high salt and polymer concentrations. However, a maximum work of adhesion, Wadh, was achieved for a submerged TERPOC with a lower salt concentration because of a higher Tgel. The Wadh was comparable to many other underwater adhesives, and therefore TERPOCs are a promising element for underwater adhesives.

It is expected that guanidinium thiocyanate, GndSCN, improves the polymer solubility compared to NaCl, as GndSCN is more weakly hydrated. Therefore, we compared TERPOCs with GndSCN and NaCl, in Chapter 6. Indeed, a higher Tgel and lower cs,cr were observed for GndSCN containing samples which resulted in clear ordered phase symmetries. The TERPOCs adapted a lamellar morphology below cs,cr, while cylinders seemed present above cs,cr. Moreover, considerably lower moduli and peak strains were found, which may be caused by the weaker electrostatic and hydrophobic interactions. Accordingly, varying the salt type is an easy tool to adjust the properties of TERPOCs which is important for adhesive development.

It was shown that materials with solely electrostatic and hydrophobic interactions can be used as underwater adhesive. To further improve the adhesive properties, it is important to lower the water content, while maintaining the deformability upon application, Chapter 7. This can be achieved by extrusion, by introducing more hydrophobic electrolytes, or by adding hydrophobic moieties into the polymer. Moreover, it can be interesting to introduce more molecular interactions, such as π- π, cation-π, or metal coordination, which can be realized by incorporating aromatic or catechol groups, such as DOPA. In addition, solidification by lowering the salt concentration after application can be explored. Over all, we believe that TERPOCs are a good candidate for the development of underwater adhesives.

Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
  • van der Gucht, Jasper, Promotor
  • Kamperman, M., Promotor
Award date15 Nov 2019
Place of PublicationWageningen
Print ISBNs9789463950633
Publication statusPublished - 2019

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