Shaping up nicely

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Science Translational Medicine  15 Apr 2015:
Vol. 7, Issue 283, pp. 283ec63
DOI: 10.1126/scitranslmed.aab2765

Ischemic and damaged tissues both require new blood vessels for repair. In the field of regenerative medicine, one strategy is to implant biodegradable materials that slowly release angiogenic factors. This process is controlled by a diverse array of biomaterial properties, including chemical characteristics and degradation profile. Berdichevski et al. reasoned that a simple yet largely unexplored implant property also would affect this process: its shape.

Current techniques to assess biomaterial breakdown and release of vessel-promoting factors in vivo require postmortem analysis, obscuring dynamic information about these processes. To overcome this limitation, the team combined two noninvasive imaging modalities to continuously monitor implant shape and volume while simultaneously measuring the release of degradation byproducts. Contrast agents for magnetic resonance imaging (MRI) and fluorescent dyes were linked to the chemical precursor components of gels. The gels were formulated into three distinct shapes, each with the same chemical properties and volume: a cylindrical plug, a dispersion of microbeads, and a precursor solution that gelled in situ as an amorphous shape. All gels were placed in the subcutaneous space of rats. MRI showed that the gel polymerized in situ disappeared the quickest, followed by microbeads, whereas cylindrical plugs remained for the longest period of time. Whole-animal fluorescence imaging tracked the release of hydrogel constituents and the proangiogenic factor vascular endothelial growth factor (VEGF). Interestingly, despite similar chemical properties and release kinetics, microbeads supported the infiltration of 16-fold more blood vessels compared with cylindrical plugs.

The biomaterials in this study were evaluated under the skin of healthy animals, and different results would be expected in other areas of the body or when disease is present. Nevertheless, these results suggest that implant geometry affects the host angiogenic response, paving the way for strategies to control blood vessel growth through implant design.

A. Berdichevski et al., Using bimodal MRI/fluorescence imaging to identify host angiogenic responses to implants. Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1502232112 (2015). [Abstract]

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