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Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering

Abstract

New generations of synthetic biomaterials are being developed at a rapid pace for use as three-dimensional extracellular microenvironments to mimic the regulatory characteristics of natural extracellular matrices (ECMs) and ECM-bound growth factors, both for therapeutic applications and basic biological studies. Recent advances include nanofibrillar networks formed by self-assembly of small building blocks, artificial ECM networks from protein polymers or peptide-conjugated synthetic polymers that present bioactive ligands and respond to cell-secreted signals to enable proteolytic remodeling. These materials have already found application in differentiating stem cells into neurons, repairing bone and inducing angiogenesis. Although modern synthetic biomaterials represent oversimplified mimics of natural ECMs lacking the essential natural temporal and spatial complexity, a growing symbiosis of materials engineering and cell biology may ultimately result in synthetic materials that contain the necessary signals to recapitulate developmental processes in tissue- and organ-specific differentiation and morphogenesis.

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Acknowledgements

We are grateful to our collaborators in angiogenesis, including V. Djornov, M. Ehrbar, H. Hall and A. Zisch, in bone regeneration, including J. Schense, H. Schmökel, F. Weber, and cell-matrix biomechanics, including G. Raeber. We thank P. Raeber for excellent work on illustrations. We apologize to all the scientists whose work we could not cite due to space restrictions.

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Competing interests

Some of the materials referenced in this work are the subject of patents and patent applications by the authors. J.A.H. holds equity in the company that has licensed these applications.

Correspondence to M P Lutolf or J A Hubbell.

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Figure 1: The behavior of individual cells and the dynamic state of multicellular tissues is regulated by intricate reciprocal molecular interactions between cells and their surroundings.
Figure 2: Design strategies for the creation of synthetic biomolecular materials that mimic the complexity of natural ECMs.
Figure 3: Examples of complex synthetic ECM mimetics proposed in Figure 2.
Figure 4: Morphogenetic steps and underlying regulatory molecules involved in endothelial cell assembly into capillary tube structures, and subsequent stabilization of tubes into mature blood vessels.