Editors' ChoiceBioengineering

Bioinspired Glue for Healing Atherosclerotic Plaques

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Science Translational Medicine  02 Jan 2013:
Vol. 5, Issue 166, pp. 166ec3
DOI: 10.1126/scitranslmed.3005531

It's always a surprise when a twig sprouts legs and walks away—as a praying mantis. Being able to mimic surroundings is a powerful tool in nature that scientists have recently been exploring in medicine. "Bioinspired" by underwater life, Kastrup and colleagues biochemically mimicked the underwater adhesives of marine mussels to develop a protective strategy for atherosclerosis.

Mussels rely on the adhesive properties of proteins that they secrete to bond to underwater surfaces. Responsible for the adhesion process is catechol, which the authors used to develop their synthetic equivalent along with polysaccharide and alginate. Covalent bonds allow the gel to adhere to cellular surfaces while simultaneously resisting shear stresses, as the authors found when the gel was administered to endothelial cells within microfluidic channels and to bovine carotid arteries lacking their endothelial lining. Kastrup et al. then applied the adhesive gel locally to the healthy carotid artery of mice. Intravital fluorescence microscopy confirmed that the gel layer remained stable and adhered for up to 4 months after treatment, without occluding the artery. The gel also stimulated the growth of endothelial and vascular smooth muscle cells, suggesting a natural healing role in blood vessels. The accompanying acute but minor inflammatory response was similar to that for biological implants. In a mouse model of atherosclerosis, atherosclerotic plaques were coated via catheter by the adhesive gel loaded with the anti-inflammatory molecule dexamethasone. The resultant cellular remodeling promoted increased stability of the fibrous cap. Panels of inflammatory markers suggested a reduction in the inflammatory response in gel-treated as compared with saline-treated mice.

Kastrup and colleagues believe that the adhesive gel technology leads to a remodeling and shielding of the inner vascular surface, which would be useful for treating atherosclerotic disease, but further mechanistic experiments will be needed to confirm this. Nevertheless, this is an important first step in mimicking the functional chemistry of marine mussels for biomedical applications. As the authors note, assessing long-term safety and efficacy in larger animals will be crucial for translation.

C. J. Kastrup et al., Painting blood vessels and atherosclerotic plaques with an adhesive drug depot. Proc. Natl. Acad. Sci. U.S.A., published online 11 December 2012 (10.1073/pnas.1217972110). [Abstract]

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