Multiple facets for extracellular matrix mimicking in regenerative medicine

In this piece, featured in the Special Focus Issue on ‘Engineering the nanoenvironment for regenerative medicine,’ Yu Shrike Zhang and Younan Xia introduce our current understanding of the potential for biomimicry of the extracellular matrix in regenerative medicine. This article highlights the critical importance that nanotechnologies will play in basic cell science and in the future design of biomaterial systems.

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Apr 01, 2015
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The extracellular matrix (ECM) refers to a complex, dynamic collection of physiologically active molecules secreted and organized by cells in a tissue [1]. In addition to its essential role in providing a structural support for the cells, the ECM also controls their division, growth and development, ultimately determining how a tissue looks and functions. It is well known that the molecular compositions of ECM vary across different tissues. While the ECMs of most tissues are built on organic compounds (mainly collagens, together with elastin, laminin, proteoglycans and many other biomolecules), those in bones contain significant amounts (>70% in dry weight) of inorganic substances derived from calcium phosphate (e.g., bioapatite), which account for the high mechanical strength of bones [2]. Besides the vast diversity in composition, the spatial arrangement of ECM molecules can be either haphazard or highly ordered depending on the type of tissue. For example, the collagen fibrils in normal skins do not show any structural order [3] while those in tendons are crimped and further organized into highly ordered structures through parallel binding via small leucine-rich proteoglycans such as decorin, lumican and fibromodulin [2,4]. Rather than being an inert filler material between cells, the ECM undergoes constant remodeling over the entire course of tissue development, especially when a tissue seeks to repair or regenerate itself after disease or injury [5].

Certain tissues such as epidermis and liver are well known for their capabilities to regenerate, whereas most others in the human body are rather limited in terms of self-regeneration power. At the intersection of biomedical engineering, life sciences, medicine and materials science, tissue regeneration has emerged as one of the most active areas of research in recent decades for its potential to restore the functionality of a tissue or even organ postdamage [6,7]. To achieve this ambitious goal, many strategies have been proposed and tested, including the application of biochemical and biophysical cues, as well as the use of pluripotent cells [6–8]. No matter which strategy is adopted, it tends to involve the use of a biomaterial in the right form (e.g., particle, fiber, porous structure or hydrogel) to offer the seeded or recruited cells a physiological microenvironment similar to what is found in the native tissue. In this so-called ECM mimicking approach, both natural (e.g., collagen, gelatin and alginate) and synthetic (e.g., poly[lactic-co-glycolic acid], polycaprolactone and poly[glycerol-sebacate]) polymers have been widely used. Thanks to the development in materials science and engineering, now it is feasible to engineer the biomaterial into any desired form with its feature size being controlled over a broad range from tens of nanometers to several centimeters. By presenting the biomaterial in a 3D architecture resembling the ECM of native tissue, it is not unreasonable to expect that the cells should be induced and directed to develop into a perfectly functional tissue [7,9]. Therefore, for successful tissue regeneration, it is of paramount importance to engineer and optimize the microenvironment around cells through the judicious selection and engineering of biomaterials, biomolecules and cells. For successful tissue regeneration, it is of paramount importance to engineer and optimize the microenvironment around cells through the judicious selection and engineering of biomaterials, biomolecules and cells….

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References

1.

Hynes RO. The extracellular matrix: not just pretty fibrils. Science 326(5957), 1216–1219 (2009).

2.

Smith L, Xia Y, Galatz LM, Genin GM, Thomopoulos S. Tissue-engineering strategies for the tendon/ligament-to-bone insertion. Connect. Tissue Res. 53(2), 95–105 (2012).

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Breitkreutz D, Mirancea N, Nischt R. Basement membranes in skin: unique matrix structures with diverse functions? Histochem. Cell Biol. 132(1), 1–10 (2009).

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Thomopoulos S, Marquez JP, Weinberger B, Birman V, Genin GM. Collagen fiber orientation at the tendon to bone insertion and its influence on stress concentrations. J. Biomech. 39(10), 1842–1851 (2006).

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Daley WP, Peters SB, Larsen M. Extracellular matrix dynamics in development and regenerative medicine. J. Cell Sci. 121(Pt 3), 255–264 (2008).

• Describes extracellular matrix remodeling events during development and wound healing.

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Khademhosseini A, Langer R, Borenstein J, Vacanti JP. Microscale technologies for tissue engineering and biology. Proc. Natl Acad. Sci. USA 103(8), 2480–2487 (2006).

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Place ES, Evans ND, Stevens MM. Complexity in biomaterials for tissue engineering. Nat. Mater. 8(6), 457–470 (2009).

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Wu SM, Hochedlinger K. Harnessing the potential of induced pluripotent stem cells for regenerative medicine. Nat. Cell Biol. 13(5), 497–505 (2011).

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Wegst UGK, Bai H, Saiz E, Tomsia AP, Ritchie RO. Bioinspired structural materials. Nat. Mater. 14(1), 23–36 (2015).

•• Comprehensive review on the design and fabrication of bioinspired, hierarchical materials that mimic the structures and architectures of their biological counterparts.

Affiliations

Yu Shrike Zhang

Biomaterials Innovation Research Center, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

Younan Xia

The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332, USA

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Nanomedicine

Journal, Future Science Group

Nanomedicine (Impact Factor: 4.889 [2015]), is an award-winning peer-reviewed journal from Future Science Group, available in both print and online formats. Published 24 times per year, Nanomedicine is a uniquely medicine-focused journal, addressing the important challenges and advances in medical nanoscale-structured material and devices, biotechnology devices and molecular machine systems and nanorobotics, delivering this essential information in concise, clear and attractive article formats. Nanomedicine is listed by Medline/PubMed, Science Citation Index Expanded, Journal Citation Reports/Science Edition, Current Contents/Life Sciences and the Biotechnology Citation Index. Professor Kostas Kostarelos (Nanomedicine Lab, University of Manchester, UK) and Professor Charles R Martin (University of Florida, FL, USA) are the journal’s Senior Editors. You can find out more about Nanomedicine on our website (http://www.futuremedicine.com/loi/nnm), including the journal’s aims and scope and details of our international editorial board.

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