Stem cells are increasingly studied because of their potential to underpin a range of novel therapies, including regenerative strategies, cell type-specific therapy and tissue repair, among others. Bionanomaterials can mimic the stem cell environment and modulate stem cell differentiation and proliferation. New advances in these fields are presented in this review by Mashinchian et al. in the Special Focus Issue ‘Engineering the nanoenvironment for regenerative medicine.’ This work highlights the importance of topography and elasticity of the nano-/micro-environment, or niche, for the initiation and induction of stem cell differentiation and proliferation.

Over the last few decades, biomaterial-based therapeutic approaches have been successfully employed in regenerative medicine for the repair of tissues [1–5]. This novel approach creates new opportunities for stem cell-based regenerative therapies and the advancement of drug delivery and discovery [2,6–8]. Inevitably, numerous people lose a part or function of their organs and tissues due to a diverse range of diseases, birth defects or accidental trauma; thus, a tremendous clinical demand exists to promote the regeneration of injured/diseased tissues. 

Continuous advances in the field of cell and tissue engineering give scientists hope for future developments of implantable tissues, for example, for skin and cartilage, which have already been commercialized or possess high commercialization potential [9]. Stem cells, including embryonic (ESCs), adult and induced pluripotent stem cells (iPSCs), are promising cell sources to underpin these novel therapies [10,11]. 

One of the most challenging aspects of regenerative medicine, both in vitro and in vivo, is how to guide stem cell differentiation toward a specific desired lineage [12–15]. In vivo, appropriate differentiation, proliferation and maintenance of potency are regulated by stem cells and their specific microenvironments (niches) [16–18]. Biomaterials can mimic the niches of stem cells and specifically effect the in vitro differentiation that is necessary for clinical application.

Consequently, research efforts have been principally devoted to understanding how a wide range of well-recognized differentiation factors (e.g., growth factors, low molecular weight chemicals, extracellular matrix [ECM] components, cell shape, matrix stiffness and mechanical forces) contribute to the stem cell microenvironment [16,19–23]. In this review, the topography that stem cells encounter will be a particular focus. The roles of niche components and architecture in regulating cell behaviors can be elucidated by simplifying the niche structure using well-defined synthetic microenvironments as artificial bioinspired models. It is possible to biomimic the 3D structures that support tissue growth and direct cell behavior through cell-ECM interactions by using natural or artificial polymeric matrices, as will be discussed [24,25]. 

In this review, we highlight new advances in the bionanomaterials field, focusing on stem cell fate together with a perspective on future applications in the next generation of regenerative medicine….

Please visit Nanomedicine online to view the article.

Nanomedicine is also on Twitter: follow us @fsgnnm now!

References

1. Shi J, Votruba AR, Farokhzad OC, Langer R. Nanotechnology in drug delivery and tissue engineering: from discovery to applications. Nano Lett. 10(9), 3223–3230 (2010).
2. Petros RA, Desimone JM. Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discov. 9(8), 615–627 (2010).
3. Serpooshan V, Zhao M, Metzler SA et al. The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction. Biomaterials 34(36), 9048–9055 (2013).
4. Badylak SF. Decellularized allogeneic and xenogeneic tissue as a bioscaffold for regenerative medicine: factors that influence the host response. Ann. Biomed. Eng. 42(7), 1517–1527 (2014).
5. Jungebluth P, Alici E, Baiguera S et al. Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet 378(9808), 1997–2004 (2011).
6. Caiazzo M, Dell'anno MT, Dvoretskova E et al. Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature 476(7359), 224–227 (2011).
7. Hubbell JA, Chilkoti A. Nanomaterials for drug delivery. Science 337(6092), 303–305 (2012).
8. Ranga A, Gjorevski N, Lutolf MP. Drug discovery through stem cell-based organoid models. Adv. Drug Deliv. Rev. 69–70, 19–28 (2014).
9. Khademhosseini A, Vacanti J, Langer R. Progress in tissue engineering. Sci. Am. 300(5), 64–71 (2009).
10. Higuchi A, Ling Q-D, Hsu S-T, Umezawa A. Biomimetic cell culture proteins as extracellular matrices for stem cell differentiation. Chem. Rev. 112(8), 4507–4540 (2012).
11. Goodridge HS. Induced pluripotent stem cell derived myeloid phagocytes: disease modeling and therapeutic applications. Drug Discov. Today 19(6), 774–780 (2014).
12. Trappmann B, Gautrot JE, Connelly JT et al. Extracellular-matrix tethering regulates stem-cell fate. Nat. Mater. 11(7), 642–649 (2012).
13. Nakagawa M, Koyanagi M, Tanabe K et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat. Biotechnol. 26(1), 101–106 (2007).
14. Marklein RA, Burdick JA. Controlling stem cell fate with material design. Adv. Mater. 22(2), 175–189 (2010).
15. Mihaylova MM, Sabatini DM, Yilmaz ÖH. Dietary and metabolic control of stem cell function in physiology and cancer. Cell Stem Cell 14(3), 292–305 (2014).
16. Alberti K, Davey RE, Onishi K et al. Functional immobilization of signaling proteins enables control of stem cell fate. Nat. Methods 5(7), 645–650 (2008).
17. Higuchi A, Ling Q-D, Chang Y, Hsu S-T, Umezawa A. Physical cues of biomaterials guide stem cell differentiation fate. Chem. Rev. 113(5), 3297–3328 (2013).
18. Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature 505(7483), 327–334 (2014).
19. Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell 126(4), 677–689 (2006).
20. Chen W, Villa-Diaz LG, Sun Y et al. Nanotopography influences adhesion, spreading, and self-renewal of human embryonic stem cells. ACS Nano 6(5), 4094–4103 (2012).
21. Guilak F, Cohen DM, Estes BT, Gimble JM, Liedtke W, Chen CS. Control of stem cell fate by physical interactions with the extracellular matrix. Cell Stem Cell 5(1), 17–26 (2009).
22. Mahmoudi M, Bonakdar S, Shokrgozar MA et al. Cell-imprinted substrates direct the fate of stem   cells. ACS Nano 7(10), 8379–8384 (2013).
23. Gattazzo F, Urciuolo A, Bonaldo P. Extracellular matrix: a dynamic microenvironment for stem cell niche. Biochim. Biophys. Acta 1840(8), 2506–2519 (2014).
24. Kretlow JD, Mikos AG. From material to tissue: biomaterial development, scaffold fabrication, and tissue engineering. AIChE J. 54(12), 3048–3067 (2008).
25. Fong EL, Watson BM, Kasper FK, Mikos AG. Building bridges: leveraging interdisciplinary collaborations in the development of biomaterials to meet clinical needs. Adv. Mater. 24(36), 4995–5013 (2012).

Author affiliations:

Omid Mashinchian

Department of Medical Nanotechnology, School of Advanced Technologies in Medicine (SATiM), Tehran University of Medical Sciences, PO Box 14177–55469, Tehran, Iran

Lesley-Anne Turner

Centre for Cell Engineering, Joseph Black Building, Institute of Biomedical & Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK

Matthew J Dalby

Centre for Cell Engineering, Joseph Black Building, Institute of Biomedical & Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK

Sophie Laurent

Department of General, Organic & Biomedical Chemistry, NMR & Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, B-7000 Mons, Belgium

Mohammad Ali Shokrgozar

National Cell Bank, Pasteur Institute of Iran, PO Box 13169–43551, Tehran, Iran

Shahin Bonakdar

National Cell Bank, Pasteur Institute of Iran, PO Box 13169–43551, Tehran, Iran

Mohammad Imani

Novel Drug Delivery Systems Department, Iran Polymer & Petrochemical Institute (IPPI), PO Box 14965/115, Tehran, Iran

Morteza Mahmoudi

Department of Nanotechnology & Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, PO Box 14155–6451, Tehran, Iran