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Additive manufacturing (AM) is increasingly gaining a presence in the pharmaceutical industry, specifically in the reconfiguration of drug delivery systems wherein new products are being developed for administering pharmaceuticals inside the body, and drug testing systems wherein complex tissues are created to analyze medical treatments. This paper proposes a novel methodology of Competitive Technology Intelligence (CTI) to uncover the evolution of new drug delivery products where additive manufacturing is present. Using the multiple linear regression analysis and hype cycle model as a conceptual basis, we processed data from scientific papers and patents indexed by Scopus and PatSnap for the period of 2004-2019. The outcomes of this study can create a relevant knowledge base for decision-making on introducing novel technologies such as AM. Industrial and academic communities are devoting important efforts toward the advancement of AM in the health industry, especially pharmaceuticals. It is expected that this technology will bring new solutions to address fundamental global health problems. However, this technology is still in its very early stage. Therefore, investments should focus on research and development (R&D) to build a solid foundation for commercialization in the next decade.

Combating necrosis, by supplying nutrients and removing waste, presents the major challenge for engineering large three-dimensional (3D) tissues. Previous elegant work used 3D printing with carbohydrate glass as a cytocompatible sacrificial template to create complex engineered tissues with vascular networks (Miller et al. 2012, Nature Materials). The fragile nature of this material compounded with the technical complexity needed to create high-resolution structures led us to create a flexible sugar-protein composite, termed Gelatin-sucrose matrix (GSM), to achieve a more robust and applicable material. Here we developed a low-range (25–37˚C) temperature sensitive formulation that can be moulded with micron-resolution features or cast during 3D printing to produce complex flexible filament networks forming sacrificial vessels. Using the temperature-sensitivity, we could control filament degeneration meaning GSM can be used with a variety of matrices and crosslinking strategies. Furthermore by incorporation of biocompatible crosslinkers into GSM directly, we could create thin endothelialized vessel walls and generate patterned tissues containing multiple matrices and cell-types. We also demonstrated that perfused vascular channels sustain metabolic function of a variety of cell-types including primary human cells. Importantly, we were able to construct vascularized human noses which otherwise would have been necrotic. Our material can now be exploited to create human-scale tissues for regenerative medicine applications. Statement of Significance Authentic and engineered tissues have demands for mass transport, exchanging nutrients and oxygen, and therefore require vascularization to retain viability and inhibit necrosis. Basic vascular networks must be included within engineered tissues intrinsically. Yet, this has been unachievable in physiologically-sized constructs with tissue-like cell densities until recently. Sacrificial moulding is an alternative in which networks of rigid lattices of filaments are created to prevent subsequent matrix ingress. Our study describes a biocompatible sacrificial sugar-protein formulation; GSM, made from mixtures of inexpensive and readily available bio-grade materials. GSM can be cast/moulded or bioprinted as sacrificial filaments that can rapidly dissolve in an aqueous environment temperature-sensitively. GSM material can be used to engineer viable and vascularized human-scale tissues for regenerative medicine applications., Graphical abstract Image, graphical abstract

Controlling the microstructure of materials by means of phase separation is a versatile tool for optimizing material properties. Phase separation has been exploited to fabricate intricate microstructures in many fields including cell biology, tissue engineering, optics, and electronics. The aim of this study was to use phase separation to tailor the spatial location of drugs and thereby generate release profiles of drug payload over periods ranging from 1 week to months by exploiting different mechanisms: polymer degradation, polymer diluent dissolution, and control of microstructure. To achieve this, we used drop-on-demand inkjet three-dimensional (3D) printing. We predicted the microstructure resulting from phase separation using high-throughput screening combined with a model based on the Flory-Huggins interaction parameter and were able to show that drug release from 3D-printed objects can be predicted from observations based on single drops of mixtures. We demonstrated for the first time that inkjet 3D printing yields controllable phase separation using picoliter droplets of blended photoreactive oligomers/monomers. This new understanding gives us hierarchical compositional control, from droplet to device, allowing release to be "dialled up" without manipulation of device geometry. We exemplify this approach by fabricating a biodegradable, long-term, multiactive drug delivery subdermal implant ("polyimplant") for combination therapy and personalized treatment of coronary heart disease. This is an important advance for implants that need to be delivered by cannula, where the shape is highly constrained and thus the usual geometrical freedoms associated with 3D printing cannot be easily exploited, which brings a hitherto unseen level of understanding to emergent material properties of 3D printing.

Controlling the microstructure of materials by means of phase separation is a versatile tool for optimizing material properties. In this study, we show that ink jet 3D printing of polymer blends gives rise to controllable phase separation that can be used to tailor the release of drugs. We predicted phase separation using high throughput screening combined with a model based on the Flory-Huggins interaction parameter, and were able to show that drug release from 3D printed structures can be predicted from observations based on single drops of mixtures. This new understanding gives us hierarchical compositional control, from droplet to device, allowing release to be ‘dialed up’ without any manipulation of geometry. This is an important advance for implants that need to be delivered by cannula, where the shape is highly constrained and thus the usual geometrical freedoms associated with 3D printing cannot be exploited, bringing a hitherto unseen level of understanding to emergent material properties of 3D printing.

The advent of additive manufacturing (AM) or 3D printing as a tool for producing multifunctional and multimaterial objects has inspired great interest from the scientific community in various engineering and biomedical fields. This chapter will explore the recent developments in biomaterials and their composites for use in 3D and 4D printing. The expanding library of bioinks, ranging from synthetic polymers to ceramics to living cells, is discussed and their deposition via a number of AM processes, including stereolithography (SLA), extrusion printing, inkjet printing, and selective laser sintering, described. Furthermore, 4D printing is introduced as an emerging technology where time is integrated within the printing process, allowing objects to change their shape or function in response to external stimuli. Finally, the novel applications of the complex bioconstructs produced are examined with emphasis on the advantages or disadvantages of this emerging technology.

Inkjet printing has been used as an Additive Manufacturing (AM) method to fabricate three-dimensional (3D) structures. However, a lack of materials suitable for inkjet printing poses one of the key challenges that impedes industry from fully adopting this technology. Consequently, many industry sectors are required to spend significant time and resources on formulating new materials for an AM process, instead of focusing on product development. To achieve the spatially controlled deposition of a printed voxel in a predictable and repeatable fashion, a combination of the physical properties of the ‘ink’ material, print head design, and processing parameters is associated. This study demonstrates the expedited formulation of new inks through the adoption of a high-throughput screening (HTS) approach. Use of a liquid handler containing multi-pipette heads, to rapidly prepare inkjet formulations in a micro-array format, and subsequently measure the viscosity and surface tension for each in a high-throughput manner is reported. This automatic approach is estimated to be 15 times more rapid than conventional methods. The throughput is 96 formulations per 13.1 working hours, including sample preparation and subsequent printability determination. The HTS technique was validated by comparison with conventional viscosity and surface tension measurements, as well as the observation of droplet ejection during inkjet printing processes. Using this approach, a library of 96 acrylate/methacrylate materials was screened to identify the printability of each formulation at different processing temperatures. The methodology and the material database established using this HTS technique will allow academic and industrial users to rapidly select the most ideal formulation to deliver printability and a predicted processing window for a chosen application.

We propose a strategy for creating tuneable 3D printed drug delivery devices. 3D printing offers the opportunity for improved compliance and patient treatment outcomes through personalisation, but bottlenecks include finding formulations that provide a choice of drug loading and release rate, are tuneable and avoid the need for surgical removal. Our solution is to exploit 3D inkjet printing freedoms. We use a reactive prodrug that can polymerize into drug-attached macromolecules during 3D printing, and by tuning the hydrophilicity we can facilitate or hinder hydrolysis, which in turn controls the drug release. To demonstrate this approach, we attach ibuprofen to 2-hydroxyethyl acrylate through a cleavable ester bond, formulate it for inkjet 3D printing, and then print to produce a solid dosage form. This allows a much higher loading than is usually achievable-in our case up to 58 wt%. Of equal importance, the 3D inkjet printing freedoms mean that our drug delivery device is highly tuneable: by selection of spacer monomers to adjust the hydrophilicity; through geometry; by spatially varying the components. Consequently, we create bespoke, hierarchical release systems, from the molecular to macro. This approach represents a new paradigm for the formulation of printable inks for drug-loaded medical devices.

Science and technology (S&T) on three-dimensional (3D) bioprinting is growing at an increasingly accelerated pace; one major challenge represents how to develop new solutions for frequent oral diseases such as periodontal problems and loss of alveolar bone. 3D bioprinting is expected to revolutionize the health industry in the upcoming years. In dentistry, this technology can become a significant contributor. This study applies a Competitive Technology Intelligence methodology to uncover the main S&T drivers in this domain. Looking at a 6-year period from 2012 to 2018 an analysis of scientific and technology production was made. Three principal S&T drivers were identified: Scaffolds development, analysis of natural and synthetic materials, and the study of scaffold characteristics. Innovative hybrid and multiphasic scaffolds are being developed to regenerate periodontal tissue and alveolar bone by combining them with stem cells from the pulp or periodontal ligament. To improve scaffolds performance, biodegradable synthetic polymers are often used in combination with bioceramics. The characteristics of scaffolds such as fiber orientation, porosity, and geometry, were also investigated. This research contributes to people interested in bringing innovative solutions to the health industry, particularly by applying state-of-the-art technologies such as 3D bioprinting, in this case for dental tissues and dental bone diseases.

© 2016 IOP Publishing Ltd. 3D printing is of great interest for tissue engineering scaffolds due to the ability to form complex geometries and control internal structures, including porosity and pore size. The porous structure of scaffolds plays an important role in cell ingrowth and nutrition infusion. Although the internal porosity and pore size of 3D printed scaffolds have been frequently studied, the surface porosity and pore size, which are critical for cell infiltration and mass transport, have not been investigated. The surface geometry can differ considerably from the internal scaffold structure depending on the 3D printing process. It is vital to be able to control the surface geometry of scaffolds as well as the internal structure to fabricate optimal architectures. This work presents a method to control the surface porosity and pore size of 3D printed scaffolds. Six scaffold designs have been printed with surface porosities ranging from 3% to 21%. We have characterised the overall scaffold porosity and surface porosity using optical microscopy and microCT. It has been found that surface porosity has a significant impact on cell infiltration and proliferation. In addition, the porosity of the surface has been found to have an effect on mechanical properties and on the forces required to penetrate the scaffold with a surgical suturing needle. To the authors' knowledge, this study is the first to investigate the surface geometry of extrusion-based 3D printed scaffolds and demonstrates the importance of surface geometry in cell infiltration and clinical manipulation.