Bioactive Scaffolds and Tissue Engineering
The highly interdisciplinary field of Tissue Engineering (TE) is benefiting from advances in the design of artificial scaffold structures on which new cells are encouraged to grow. The ability to control topography and chemistry at the nanoscale offers exciting possibilities for stimulating growth of new tissue through the development of novel nanostructured scaffolds that mimic the nanostructure of the tissues in the body. Prof Stevens is currently co-Director of the UK’s Regenerative Medicine Programme Hub for Acellular Biomaterials established in October 2013. The Stevens group is very active in developing bioactive nanomaterials, nanocomposites and hydrogels for musculoskeletal and cardiac tissue regeneration as well as applications in neuroscience. We have also developed new approaches to regenerate organs using an
in vivo tissue engineering approach.
The goal of regenerating failing organs, before the body as a whole is ready to surrender, is now timelier than ever. Much is known about the cell microenvironment and materials engineering and yet the gap between these disciplines is immense. The Stevens group takes the approach of exploring the cell-material interface as well as engineering it to deliver a new generation of cell-instructive biomaterials. We have made key advances in the development of cell instructive new tissue engineering scaffolds based on polymeric and inorganic materials (and their composites), which build on fundamental studies aimed at elucidating the effects of specific physical and chemical cues on cell behaviour. Some examples of these advancements have been made in engineering materials for bone tissue regeneration including translation to clinic.
Highlights
• An
in vivo approach to bone regeneration involves implanting a gel between the periosteum and underlying bone, which enables new bone to be easily harvested for transplantation [
Stevens, Marini, Langer, Shastri, 2005]. This approach circumvents many of the disadvantages of harvesting bone from other sites (i.e. iliac crest).
Adapted from graphic by John Bradley at The Independent
• The Stevens group is developing biomaterials based on strontium and other ions for applications in bone and cartilage regeneration. The Stevens group has shown that such bioactive glasses support normal cell attachment and adhesion [
O’Donnell, Candarlioglu, Miller, Gentleman and Stevens, 2010] whilst they increase proliferation and alkaline phosphatase activity of cultured osteoblasts (anabolic effect) and inhibit osteoclast activity by reducing tartrate resistant acid phosphatase activity (anti-catabolic effect) [
Gentleman, Fredholm, Jell, Lotfibakhshaiesh, O'Donnell, Hill and Stevens, 2010].
• Hydrogels constitute a major class of biomaterials because their physical and chemical properties often mimic those of the native extracellular matrix tissues. The Stevens group has developed a number of innovative hydrogel designs for applications in cartilage [
Place, Nair, Chia, Szulgit, Lim and Stevens, 2012] and bone [
Place, Rojo, Gentleman, Sardinha and Stevens, 2011], whilst fibrous scaffolds have also been developed with a number of clinical targets [
Dong, Yong, Liao, Chan, Stevens and Ramakrishna, 2010; McCullen, Autefage, Callanan, Gentleman and Stevens, 2012;
Gentilini, Dong, May, Goldoni, Clarke, Lee, Pashuck and Stevens, 2012;
Chung, Gentilini, Callanan, Hedegaard, Hassing and Stevens, 2013]. We are now also working very actively on the development of new materials for cardiac regeneration within the British Heart Foundation centre of excellence at Imperial College. Important aspects regarding their translation to the clinic include surpassing scientific, regulatory and business challenges [
Pashuck and Stevens, 2012].
Key Publications
C. Horejs, J.-P. St-Pierre, J.R.M. Ojala, J.A.M. Steele, P.B. da Silva, A. Rynne-Vidal, S.A. Maynard, C.S. Hansel, C. Rodríguez-Fernández, M.M. Mazo, A.Y.F. You, A.J. Wang, T. von Erlach, K. Tryggvason, M. López-Cabrera and M.M. Stevens
"
Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information."
Nature Communications. 2017. 8: 15509.
N. Reznikov, J.A.M. Steele, P. Fratzl, M.M. Stevens
"
A materials science vision of extracellular matrix mineralization."
Nature Reviews Materials. 2016. 1: 16041.
S. Crowder, V. Leonardo, T. Whittaker, P. Papathanasiou, M.M. Stevens
"
Material Cues as Potent Regulators of Epigenetics and Stem Cell Function."
Cell Stem Cell. 2016. 18(1): 39-52.
N. Amdursky, X. Wang, P. Meredith, D.D.C. Bradley, M.M. Stevens
"
Long-range proton conduction across free-standing serum albumin mats."
Advanced Materials. 2016. 28(14): 2692-2698.
H. Autefage, E. Gentleman, E. Littmann, M.A.B. Hedegaard, T. Von Erlach, M. O’Donnell, F.R. Burden, D.A. Winkler, M.M. Stevens
"
Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials."
Proceedings of the National Academy of Sciences of the United States of America. 2015. 112(14): 4280-4285.
C. Horejs, A. Serio, A. Purvis, A.J. Gormley, S. Bertazzo, A. Poliniewicz, A.J. Wang, P. DiMaggio, E. Hohenester, M.M. Stevens
"
Biologically-active laminin-111 fragment that modulates the epithelial-to-mesenchymal transition in embryonic stem cells."
Proceedings of the National Academy of Sciences of the United States of America. 2014. 111(16): 5908-5913.
C. Gentilini, Y. Dong, J.R. May, S. Goldoni, D.E. Clarke, B.H. Lee, E.T. Pashuck, M.M. Stevens
“
Functionalized poly(γ-glutamic acid) fibrous scaffolds for tissue engineering.”
Advanced Healthcare Materials. 2012. 1: 308-15.
E.T. Pashuck, M.M. Stevens
"
Designing regenerative biomaterial therapies for the clinic."
Science Translational Medicine. 2012. 4(160): 1-12.
E.S. Place, L. Rojo, E. Gentleman, J.P. Sardinha, M.M. Stevens
“
Strontium- and zinc-hydrogels for bone tissue engineering.”
Tissue Engineering Part A. 2011. 17:2713-2722.
S.D. McCullen, A.G. Chow, M.M. Stevens
“
In vivo tissue engineering of musculoskeletal tissues.”
Current Opinion in Biotechnology. 2011. 21:715-720.
M.D. Ball, I.C. Bonzani, M.J. Bovis, A. Williams, M.M. Stevens.
"
Human periosteum is a source of cells for orthopaedic tissue engineering: a pilot study.”
Clinical Orthopaedics and Related Research. 2011. 469: 3085-3093.
E. Gentleman, Y.C. Fredholm, G. Jell, M.D. O’Donnell, N. Lotfibakhshaiesch, R.G. Hill, M.M. Stevens
"
The Effects of Strontium-Substituted Bioactive Glasses on Osteoblasts and Osteoclasts in vitro."
Biomaterials. 2010. 31(14): 3949-3956.
E.S. Place, N.D. Evans, M.M. Stevens
"
Complexity in biomaterials for tissue engineering."
Nature Materials. 2009. 8: 457-470.
I.C. Bonzani, R. Adhikari, S. Houshyar, R. Mayadunne, P. Gunatillake, M.M. Stevens
"
Synthesis of two-component injectable polyurethanes for bone tissue engineering."
Biomaterials. 2007. 28(3): 423-33.
M.M. Stevens, R.P. Marini, D. Schaefer, J. Aronson, R. Langer, V.P. Shastri
"
In vivo engineering of organs: the bone bioreactor."
Proceedings of the National Academy of Sciences of the United States of America. 2005. 102: 11450-11455.
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