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Design principles for therapeutic angiogenic materials

Abstract

Despite extensive research, pro-angiogenic drugs have failed to translate clinically, and therapeutic angiogenesis, which has potential in the treatment of various cardiovascular diseases, remains a major challenge. Physiologically, angiogenesis — the process of blood-vessel growth from existing vasculature — is regulated by a complex interplay of biophysical and biochemical cues from the extracellular matrix (ECM), angiogenic factors and multiple cell types. The ECM can be regarded as the natural 3D material that regulates angiogenesis. Here, we leverage knowledge of ECM properties to derive design rules for engineering pro-angiogenic materials. We propose that pro-angiogenic materials should be biomimetic, incorporate angiogenic factors and mimic cooperative interactions between growth factors and the ECM. We highlight examples of material designs that demonstrate these principles and considerations for designing better angiogenic materials.

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Figure 1: Clinical overview of cardiovascular diseases and pro-angiogenic factor-based therapies.
Figure 2: Multiscale microenvironmental regulation of angiogenesis.
Figure 3: Molecular changes directly regulate spatial cues within tissues.
Figure 4: Perturbation of extracellular matrix-mediated regulation of angiogenesis in disease.
Figure 5: Design rules for the development of pro-angiogenic materials.
Figure 6: Delivery systems for angiogenic factors.

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Acknowledgements

This work was supported by a US Department of Defense (DoD) National Defense Science & Engineering Graduate (NDSEG) Fellowship to L.E.C., by NIH R01HL101200, NIH R00HL093219, and a Sloan Research Fellowship to F.M.G., and by the grant Cytrix from the European Research Council to J.A.H.

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Briquez, P., Clegg, L., Martino, M. et al. Design principles for therapeutic angiogenic materials. Nat Rev Mater 1, 15006 (2016). https://doi.org/10.1038/natrevmats.2015.6

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