Cover Image: Issue 1, Materials TodayStrategies to create synthetic tissue are centred around the fabrication of scaffold structures that support cell life. In contrast to trying to directly replace the complex functions and extraordinary properties of biological tissues, such scaffolds are designed to facilitate the healthy growth of cell populations thereby indirectly restoring function. To achieve this, tissue scaffolds have to conform to numerous demanding requirements.
Most apparent is the need for the scaffold material to be biocompatible. Generally, this requires that the scaffold does not get rejected by the host or induce toxicity to populating cells and the surrounding tissue. Accordingly, the scaffold should allow cells to directly interact with the scaffold surface, supporting both cell migration and attachment throughout. Following cell attachment some tissue scaffolds are designed with cues that further direct biological behaviours inducing cell maturation, biochemical production and the differentiation of proliferating stem cells to one of the many different tissue types. To achieve this, the scaffolds must also allow for the transport of nutrients, waste and other essential proteins to cells while supporting the dynamic mechanical and rheological forces present in vivo. Finally, the scaffolds must have a similar architecture to the tissue being replaced. Such a stringent set of criteria severely limits the materials which are suitable for such an application and as a consequence researchers are on the constant look out for materials with potential for application.
Nanomaterials have shown the potential for use in synthetic tissue scaffolds. The potential of nanomaterials stems from their extraordinary chemical, electrical, optical and physical properties which are not available to the same material at larger scales. By leveraging these properties researchers have already demonstrated numerous biotechnological applications. This includes improvements to cancer therapies, bio-imaging, drug and gene delivery, pathogen and protein biosensing and cosmetic products [1].
From a tissue engineering perspective, nanomaterials have more to offer than their unique properties. This is a result of the inherent characteristics of biological systems. Because such systems are built from an assembly of nanoscale proteins, building tissue scaffolds from nanomaterials gives tissue engineers the opportunity to incorporate similar levels of detail into synthetic environments. Consequently such ‘nanobiomaterials’ have the potential to more accurately reproduce the natural cellular environment.
Carbon nanotubes(CNTs) is one of the nanomaterials that has attracted a lot of interest for use in tissue scaffolds. These tiny graphitic tubes have shown in vivo biocompatibility as a bulk material, in composites or in solution [2]. Additionally, their versatile properties have led to tissue scaffolding applications for many different tissues including bone [2], cartilage [3], muscle [4] and nerve tissue [5]. This versatility reflects in the properties such as their extraordinary strength, controllable diameter and lengths, conducting or semi-conducting electronic properties, ability to be functionalized with simple or complex functional groups including DNA and other biochemicals and ability to be scaled up into higher dimensional micro- or macroscale fibres or sheets [2].
The cover image shows a three-dimensional bone scaffold fabricated with carbon nanotubes. Adipose derived stem cells can be seen proliferating over its surface with cell protrusions stretching over a carbon nanotube forest and between the struts of the bone-like structure. This image was taken using a field emission scanning electron microscope (Zeiss Ultra Plus, Germany; secondary electron detector, 450×, 5 kV) at the Australian Centre for Microscopy and Microanalysis Facility, The University of Sydney.
The sample was prepared by a two-step process. Firstly, a porous ceramic core was prepared by the replication technique [6]. This was followed by the growth of the CNT forest using chemical vapour deposition [7]. Once prepared, adipose derived stem cells were cultured over the sample under standard culturing conditions. These cells were later fixed and dehydrated for microscopy.
This scaffold has been developed at the Tissue Engineering and Biomaterials Research Unit, The University of Sydney. It has been designed for use in load-bearing applications for regeneration of segmental bone defects. Its high strength and bioactivity are combined with a high porosity (∼85%) and pore size (∼400 μm) to allow for the sufficient transport of nutrients and waste, cell migration, attachment and proliferation [6]. The tubular nanoscale dimensions of the CNTs mimic that of the natural collagen fibres that compose a large fraction of the bone extracellular environment.
Acknowledgments
The authors acknowledge the following organization for support: Commonwealth Government – Australian Postgraduate Award Scholarship; The Australian National Health and Medical Research Council; Rebecca Cooper Foundation; Australian Research Council.
Further reading
[1] R. Singh, H.S. Nalwa J. Biomed. Nanotechnol., 7 (4) (2011), pp. 489–503
[2] P. Newman et al. Carbon nanotubes: their potential and pitfalls for bone tissue regeneration and engineering. Nanomedicine (UK), 9 (2013), pp. 1139–1158 (Epub 2013/06/19)
[3] N. Ogihara et al. Biocompatibility and bone tissue compatibility of alumina ceramics reinforced with carbon nanotubes. Nanomedicine (UK), 7 (7) (2012), pp. 981–993
[4 ]A.F. Quigley et al. Electrical stimulation of myoblast proliferation and differentiation on aligned nanostructured conductive polymer platforms. Adv. Healthc. Mater., 1 (6) (2012), pp. 801–808
[5]H. Hu et al. Chemically functionalized carbon nanotubes as substrates for neuronal growth. Nano Lett., 4 (3) (2004), pp. 507–511
[6] S.I. Roohani-Esfahani et al. Unique microstructural design of ceramic scaffolds for bone regeneration under load. Acta Biomater., 9 (6) (2013), pp. 7014–7024
[7] X.S. Yang et al. Open-ended aligned carbon nanotube arrays produced using CO2-assisted floating-ferrocene chemical vapor deposition. J. Phys. Chem. C, 115 (29) (2011), pp. 14093–14097