Bioadhesives

Bioadhesives are natural polymeric materials that act as adhesives. The term is sometimes used more loosely to describe a glue formed synthetically from biological monomers such as sugars, or to mean a synthetic material designed to adhere to biological tissue.

Bioadhesives may consist of a variety of substances, but proteins and carbohydrates feature prominently. Proteins such as gelatin and carbohydrates such as starch have been used as general-purpose glues by man for many years, but typically their performance shortcomings have seen them superseded by synthetic alternatives. Highly effective adhesives found in the natural world are currently under investigation but not yet in widespread commercial use. For example, bioadhesives secreted by microbes and by marine molluscs and crustaceans are being researched with a view to biomimicry. [Smith, A.M. & Callow, J.A., eds. (2006) "Biological Adhesives." Springer, Berlin. ISBN 978-3-540-31048-8]

Bioadhesives are of commercial interest because they tend to be biocompatible, i.e. useful for biomedical applications involving skin or other body tissue. Some work in wet environments and under water, while others can stick to low surface energy/ non-polar surfaces like plastics. In recent years, the synthetic adhesives industry has been impacted by environmental concerns and health/safety issues relating to hazardous ingredients, volatile organic compound emissions, and difficuties in recycling or remediating adhesives derived from petrochemical feedstocks. Rising oil prices may also stimulate commercial interest in biological alternatives to synthetic adhesives.

Examples of bioadhesives in nature

Organisms may secrete bioadhesives for use in attachment, construction and obstruction, as well as in predation and defense. Examples [Graham, L.D. (2008) Biological adhesives from nature. In: "Encyclopedia of Biomaterials and Biomedical Engineering", 2nd ed., Eds. Wnek, G. & Bowlin, G., Informa Healthcare, New York & London, vol. 1, p.236-253. [http://www.informaworld.com/smpp/432725899-68817976/content~content=a738105315~db=all~order=title Online abstract] ] include their use for
* colonization of surfaces (e.g. bacteria, algae, fungi, mussels, barnacles)
* tube building by polychaete worms, which live in underwater mounds
* insect egg, larval or pupal attachment [Li, D., Huson, M.G. & Graham, L.D. (2008) Proteinaceous adhesive secretions from insects, and in particular the egg attachment glue of "Opodiphthera" sp. moths. "Arch. Insect Biochem. Physiol." 69, 85-105. DOI: 10.1002/arch.20267] to surfaces (vegetation, rocks), and insect mating plugs
* host attachment by blood-feeding ticks
* nest-building by some insects, and also by some fish (e.g. the three-spined stickleback)
* defense by "Notaden" frogs and by sea cucumbers
* prey capture in spider webs and by velvet worms

Some bioadhesives are very strong. For example, adult barnacles achieve pull-off forces as high as 2 MPa (2 N/mm²).
Silk dope can also be used as a glue by arachnids and insects.

Temporary Adhesion

Organisms such as limpets and sea stars use suction and mucus-like slimes to create Stefan Adhesion, which makes pull-off much harder than lateral drag; this allows both attachment and mobility. Spores, embryos and juvenile forms may use temporary adhesives (often glycoproteins) to secure their initial attachment to surfaces favorable for colonization. Tacky and elastic secretions that act as pressure sensitive adhesives, forming immediate attachments on contact, are preferable in the context of self-defense and predation. Molecular mechanisms include non-covalent interactions and polymer chain entanglement. Many biopolymers - proteins, carbohydrates, glycoproteins, and mucopolysaccharides - may be used to form hydrogels that contribute to temporary adhesion.

Permanent Adhesion

Many permanent bioadhesives (e.g., the oothecal foam of the mantis) are generated by a "mix to activate" process that involves hardening via covalent cross-linking. On non-polar surfaces the adhesive mechanisms may include van der Waals forces, whereas on polar surfaces mechanisms such as hydrogen bonding and binding to (or forming bridges via) metal cations may allow higher sticking forces to be achieved.
* Microorganisms use acidic polysaccharides (molecular mass around 100 000 Da)Fact|date=January 2008
* Marine bacteria use carbohydrate exopolymers to achieve bond strengths to glass of up to 500 000 N/m²Fact|date=January 2008
* Marine inverterbrates commonly employ protein-based glues for irreversible attachment. Some mussels achieve 800 000 N/m² on polar surfaces and 30 000 N/m² on non-polar surfacesFact|date=January 2008
* Some algae and marine invertebrates use polyphenolic proteins containing L-DOPA
* Proteins in the oothecal foam of the mantis are cross-linked covalently by small molecules related to L-DOPA via a tanning reaction that is catalysed by catechol oxidase or polyphenol oxidase enzymes.

L-DOPA is a tyrosine residue that bears an additional hydroxyl group. The twin hydroxyl groups in each side-chain compete well with water for binding to surfaces, form polar attachments via hydrogen bonds, and chelate the metals in mineral surfaces. The Fe(L-DOPA₃) complex can itself account for much cross-linking and cohesion in mussel plaque, [Sever M.J.; Weisser, J.T.; Monahan, J.; Srinivasan, S.; Wilker, J.J. (2004) Metal-mediated cross-linking in the generation of a marine-mussel adhesive. "Angew. Chem. Int. Ed." 43 (4), 448-450] but in addition the iron catalyses oxidation of the L-DOPA [Monahan, J.; Wilker, J.J. (2004) Cross-linking the protein precursor of marine mussel adhesives: bulk measurements and reagents for curing. "Langmuir" 20 (9), 3724-3729] to reactive quinone free radicals, which go on to form covalent bonds. [Deming, T.J. (1999) Mussel byssus and biomolecular materials. "Curr. Opin. Chem. Biol." 3 (1), 100-105]

Commercial Applications

Shellac is an early example of a bioadhesive put to practical use. Additional examples now exist, with others in development:
* Commodity wood adhesive based on a bacterial exopolysaccharide [Combie, J., Steel, A. and Sweitzer, R. (2004) Adhesive designed by nature (and tested at Redstone Arsenal). "Clean Technologies and Environmental Policy" 5 (4), 258-262. [http://www.springerlink.com/content/82n99965k3l9er7u/ Abstract] ]
* USB PRF/Soy 2000, a commodity wood adhesive that is 50% soy hydrolysate and excels at finger-jointing green lumber [ [http://www.unitedsoybean.org/UploadedFiles/Library/pdf_25241T%20Scheids%20PRF.pdf USB flyer] ]
* Mussel adhesive proteins can assist in attaching cells to plastic surfaces in laboratory cell and tissue culture experiments (see External Links)
* The "Notaden" frog glue is under development for biomedical uses, e.g. as a surgical glue for orthopedic applications or as a hemostat [Graham, L.D.; Glattauer, V.; Huson, M.G.; Maxwell, J.M.; Knott, R.B.; White, J.W.; Vaughan, P.R.; Peng, Y.; Tyler, M.J.; Werkmeister, J.A.; Ramshaw, J.A. (2005) Characterization of a protein-based adhesive elastomer secreted by the Australian frog "Notaden bennetti". "Biomacromolecules" 6, 3300-12. [http://pubs.acs.org/cgi-bin/abstract.cgi/bomaf6/2005/6/i06/abs/bm050335e.html Abstract] ]
* Mucosal drug delivery applications. For example, films of mussel adhesive protein give comparable mucoadhesion to polycarbophil, [Schnurrer, J.; Lehr, C.M. (1996) Mucoadhesive properties of the mussel adhesive protein. "Int. J. Pharmaceutics" 141 (1-2), 251-256] a synthetic hydrogel used to achieve effective drug delivery at low drug doses.

Several commercial methods of production are being researched:
* direct chemical synthesis, e.g. incorporation of L-DOPA groups in synthetic polymers [Huang, K.; Lee, B.P.; Ingram, D.R.; Messersmith, P.B. (2002) Synthesis and characterization of self-assembling block copolymers containing bioadhesive end groups. "Biomacromolecules" 3 (2), 397-406]
* fermentation of transgenic bacteria or yeasts that express bioadhesive protein genes
* farming of natural organisms (small and large) that secrete bioadhesive materials

References

External links

* [http://www.bdbiosciences.com/discovery_labware/products/display_product.php?keyID=227 Cell-Tak] , a mussel adhesive protein preparation sold for use in cell and tissue culture.
* "Mussels inspire new surgical glue possibilities". [http://www.sciencedaily.com/releases/2007/12/071206230814.htm ScienceDaily] article, Dec 2007.
* [http://www.abc.net.au/catalyst/stories/s1705318.htm Frog glue] story on ABC TV science program "Catalyst".
* "Marine algae hold key to better biomedical adhesives", [ftp://ftp.cordis.europa.eu/pub/nmp/docs/biomaterials_web.pdf "Biomaterials for healthcare: a decade of EU-funded research"] , p.23
* [http://lepton.marz.com/ncga/comm_dev_center/product_supplier.asp?ProdSup=ECOSYNTHETIX+Adhesives%2C+Inc. New adhesives] including ones from cornstarch and a sugar-based pressure-sensitive adhesive.
* [http://www.informaworld.com/smpp/432725899-68817976/content~content=a738105315~db=all~order=title Review] of bioadhesives from 2005.