Brasinika D1,2 Gkartzou E1 Koumoulos E1,2 Charitidis CA1,2,*1Research Unit of Advanced, Composite, Nano-Materials and Nanotechnology, School of Chemical Engineering, National Technical University of Athens, Greece
2BioGen3D-New 3D Printing Technologies, Technological Cultural Park Lavrion, Greece
*Corresponding author: Charitidis CA, Research Unit of Advanced, Composite, Nano-Materials and Nanotechnology, School of Chemical Engineering, National Technical University of Athens, Greece, E-mail: firstname.lastname@example.org
Pressure-assisted Direct Ink Writing (p-DIW) technologies have widely attracted the interest of many researchers for the fabrication of 3D printed personalised implants with improved biofunctionality and defined micro architecture in the field of regenerative medicine . This Additive Manufacturing (AM) technique presents high versatility in the materials that can be employed as bio inks, including natural and synthetic biopolymers, hybrid hydro gels and nanostructured or nanocomposites materials. In this context, by introducing innovative bio inks, which have been synthesised through bio inspired approaches simulating the bio mineralization process, p-DIW can lead to complex hybrid scaffolds with bone-like nanostructure. Mimicking natural bone’s composition and crystallinity, significantly improves the cytocompatibility of the final scaffolds, providing a suitable microenvironment for cell proliferation and differentiation, and thus leading to enhanced osteointegration of the implant . These structures could serve as a 3D template to guide the regeneration process of tissues, while maintaining mechanical integrity until the tissue regenerates naturally.
P-DIW combined with computer-assisted design could be exploited to create 3D scaffolds with defined internal multi-scale porosity, through a fully automated process with accuracy and repeatability. The formation of a continuous porous network with bimodal pore size distribution (both in the micro- and macro scale) and high levels of interconnectivity, considerably promotes the mineralized tissue in growth and vascularization [3,4]. Small pores ensure bone oxygenation, angiogenesis and nutrient and waste diffusion, while the larger ones are important in cellular development, orientation and directionality of cellular in growth and consequently are responsible of the scaffold’s bioactivity.
A substantial advantage of computer-assisted design is based on the capability to design personalised implants which conform to the physical and biomechanical requirements of the host bones . The design process of these complex structures begins with the acquisition of Computer Tomography (CT) or Magnetic Resonance Imaging (MRI) 2D image datasets, which can be imported and processed in specialized software to create a surface-rendered 3D volumetric model of the area of the bone defect, in order to determine the anatomical and micro structural characteristics that will define the external shape and internal micro architecture of the implant, as well as the precise site of insertion. This multi-scale hierarchical microstructure can be further enhanced through topological optimisation of the scaffolds .
The (nano) mechanical behaviour of 3D printed scaffolds is of relevant interest in applications which require not only load-bearing capability, but also need for assessing the surface adhesion and time dependent deformation. Typically, nanoindentation studies are carried out spanning different penetration depth on bulk (pore-free) materials and on the walls of porous scaffolds . Nanomechanical mapping investigations is a promising method and allows assessing small-scale integrity of the scaffold walls . Additionally, a characteristic nano indentation adhesion test is comprised of pressing the tip into the patterned sample, followed by unloading it at a constant rate and finally obtaining a distinctive (and often abrupt) pull-off force representing the adhering surfaces. Adhesion is observed in a load-displacement curve as a region of negative load during unloading . The principle of this experiment is to put into contact the diamond probe tip and the flat polymer substrate and determine the maximum pull-force necessary to separate both materials. Quantitative assessment of mechanical behaviour is now possible for materials that were previously unattainable , especially for biomaterials that are hierarchical in structure. A key feature in this method is the selection of appropriate (often prototypes or modified) tip geometries and testing protocols.
The aforementioned combinatorial methodology constitutes a promising holistic approach for the automated fabrication of fully cytocompatible 3D printed scaffolds, targeting at tissue regeneration and not a temporary replacement of the damaged bone. Additionally, such AM processes ensure material waste minimization  and the inherent biodegradability of the bio inks employed renders them an environmental friendly solution. This innovative type of treatment decreases the risk of possible clinical complications (e.g. inflammatory response and subsequent rejection of the implant), since the 3D printed implant is in vitro seeded with cells extracted from small biopsies from the host before implantation, and the overall surgical costs are also reduced. The standardization and certification of this process are expected to pave the way towards a scaled-up production of patient-specific scaffolds, offering a viable solution to the worldwide increasing demand of compatible donors and/or improved implants.
- Billiet T, Vandenhaute M, Schelfhout J, Vlierberghe SV, Dubruel P (2012) A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering. Biomaterials 33: 6020-6041. [Ref.]
- Brasinika D, Tsigkou O, Tsetsekou A, Missirlis YF (2016) Bioinspired synthesis of hydroxyapatite nanocrystals in the presence of collagen and l-arginine: Candidates for bone regeneration. J Biomed Mater Res B Appl Biomater 104: 458-469. [Ref.]
- LiuY, LiX, QuX, ZhuL, HeJ, et al. (2012) The fabrication and cell culture of three-dimensional rolled scaffolds with complex microarchitectures. Biofabrication 4: 015004-015017. [Ref.]
- HuangY, HeJ, GaL, LiuX, WuY, et al. (2014) Osteoconductivity and osteoinductivity of porous hydroxyapatite coatings deposited by liquid precursor plasma spraying: in vivo biological response study. Biomed Mater 9: 065007-065017. [Ref.]
- Parthasarathy J (2014) 3D modeling, custom implants and its future perspectives in craniofacial surgery. Ann Maxillofac Surg 4: 9-18. [Ref.]
- WangX, XuS, ZhouS, XuW, LearyM, et al. (2016) Topological design and additive manufacturing of porous metals for bone scaffolds and orthopaedic implants: A review. Biomaterials 83: 127-141. [Ref.]
- Shahgholi M, Oliviero S, Baino F, Vitale-Brovarone C, Gastaldi D, et al. (2016) Mechanical characterization of glass-ceramic scaffolds at multiple characteristic lengths through nanoindentation. J Eur Ceram Soc 36: 2403-2409. [Ref.]
- Koumoulos E, Charitidis C (2017) Surface analysis and mechanical behaviour mapping of vertically aligned CNT forest array through nanoindentation. Appl Sur Sci 396: 681-687. [Ref.]
- Koumoulos E, Jagadale P, Lorenzi A, Tagliaferro A, Charitidis C (2015) Evaluation of surface properties of epoxy–nanodiamonds composites. Composites B 80: 27-36. [Ref.]
- Ebenstein D, Pruitt L (2006) Nanoindentation of biological materials. Nano Today 1: 26-33. [Ref.]
- Gkartzou E, Koumoulos EP, Charitidis C (2017) Production and 3D Printing Processing of Bio-based Thermoplastic Filament. Manufacturing Rev. 4: 1-14. [Ref.]
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Article Type: Mini Review
Citation: Brasinika D, Gkartzou E, Koumoulos E, Charitidis CA (2017) Pressure-assisted Direct Ink Writing: A promising approach for the fabrication of Personalised Biofunctional Scaffolds. Int J Nanomed Nanosurg 3(1): doi http://dx.doi.org/10.16966/2470- 3206.121
Copyright: © 2016 Brasinika D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.