A Reactive Prodrug Ink Formulation Strategy for Inkjet 3D Printing of Controlled Release Dosage Forms and Implants

He, Yinfeng; Foralosso, Ruggero; Trindade, Gustavo F.; Ilchev, Alexander; Ruiz‐Cantu, Laura; Clark, Elizabeth A.; Khaled, Shaban A.; Hague, Richard; Tuck, Christopher; Rose, Felicity R. A. J.; Mantovani, Giuseppe; Irvine, Derek J.; Roberts, Clive J.; Wildman, Ricky

doi:10.1002/adtp.201900187

Cited by 19 publications

(12 citation statements)

References 43 publications

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“…A trial printing of the remaining materials was then conducted to determine the reliability of printing and whether the materials would cure on our printing configuration. From this we selected two materials that showed the greatest promise for successful printing and proceeded to optimise the formulations ready for scale up [25][26][27][28] ( Supplementary Table S1): tricyclo[5.2.1.02,6]decanedimethanol diacrylate (TCDMDA) and ethylene glycol dicyclopentenyl ether acrylate (EGDPEA). Sixteen formulations were then investigated where the photoinitiator and the candidate monomers were combined covering a breadth of utility in different environments and potential reaction speeds (Supplementary Table S2) as both could influence the product performance [22,[29][30][31] .…”

Section: Resultsmentioning

confidence: 99%

“…printer nozzles. In order to maximise printability, inks were sealed and stored at 4°C overnight to help release any bubbles generated during preparation [27] .…”

Section: Discussionmentioning

confidence: 99%

“…Table S1: Monomers that have shown resistance to bacterial biofilm resistance after polymerization were selected from polymer library and tested using our Dimatix DMP 2830 printing platform to assess if they are printable and curable in IJ3DP process. Printability is assumed within the range 1 < Z < 10 [27] and then an assessment of whether reliable and consistent printing was possible was made by manual observation of the droplet formation and deposition. Curing was assessed by observing whether a 3D printed material was self-supporting.…”

Section: Mouse Foreign Body Infection Modelmentioning

confidence: 99%

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Inkjet based 3D Printing of bespoke medical devices that resist bacterial biofilm formation

Begines

Dubern

et al. 2020

Preprint

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AbstractWe demonstrate the formulation of advanced functional 3D printing inks that prevent the formation of bacterial biofilms in vivo. Starting from polymer libraries, we show that a biofilm resistant object can be 3D printed with the potential for shape and cell instructive function to be selected independently. When tested in vivo, the candidate materials not only resisted bacterial attachment but drove the recruitment of host defences in order to clear infection. To exemplify our approach, we manufacture a finger prosthetic and demonstrate that it resists biofilm formation – a cell instructive function that can prevent the development of infection during surgical implantation. More widely, cell instructive behaviours can be ‘dialled up’ from available libraries and may include in the future such diverse functions as the modulation of immune response and the direction of stem cell fate.

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Section: Resultsmentioning

confidence: 99%

“…printer nozzles. In order to maximise printability, inks were sealed and stored at 4°C overnight to help release any bubbles generated during preparation [27] .…”

Section: Discussionmentioning

confidence: 99%

Section: Mouse Foreign Body Infection Modelmentioning

confidence: 99%

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Inkjet based 3D Printing of bespoke medical devices that resist bacterial biofilm formation

Begines

Dubern

et al. 2020

Preprint

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“…In recent decades, 3D printing has been recognised by many to be an answer to this call and the future of polypharmacy [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. The possibility to mass-produce personalised components without substantially increasing production time or costs makes 3D printing an attractive proposition [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Customisable Tablet Printing: The Development of Multimaterial Hot Melt Inkjet 3D Printing to Produce Complex and Personalised Dosage Forms

et al. 2021

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One of the most striking characteristics of 3D printing is its capability to produce multi-material objects with complex geometry. In pharmaceutics this translates to the possibility of dosage forms with multi-drug loading, tailored dosing and release. We have developed a novel dual material hot-melt inkjet 3D printing system which allows for precisely controlled multi-material solvent free inkjet printing. This reduces the need for time-consuming exchanges of printable inks and expensive post processing steps. With this printer, we show the potential for design of printed dosage forms for tailored drug release, including single and multi-material complex 3D patterns with defined localised drug loading where a drug-free ink is used as a release-retarding barrier. For this, we used Compritol HD5 ATO (matrix material) and Fenofibrate (model drug) to prepare both drug-free and drug-loaded inks with drug concentrations varying between 5% and 30% (w/w). The printed constructs demonstrated the required physical properties and displayed immediate, extended, delayed and pulsatile drug release depending on drug localisation inside of the printed formulations. For the first time, this paper demonstrates that a commonly used pharmaceutical lipid, Compritol HD5 ATO, can be printed via hot-melt inkjet printing as single ink material, or in combination with a drug, without the need for additional solvents. Concurrently, this paper demonstrates the capabilities of dual material hot-melt inkjet 3D printing system to produce multi-material personalised solid dosage forms.

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“…In principle, material composition can be varied on a voxel or droplet basis. which opens the possibility of a next generation of 3DP that allows the user to produce devices with spatially distributed, customizable material functionalities in a cost-effective manner [10][11][12][13][14] . This paper sets out to develop a platform by which MM-IJ3DP can be used to create bespoke devices with tuneable, spatially varying mechanical performance, whilst incorporating and retaining cell-instructive functions -in this case resistance to bacterial biofilm formation.…”

Section: Introductionmentioning

confidence: 99%

Exploiting Generative Design for Multi-Material Inkjet 3D Printed Cell Instructive, Bacterial Biofilm Resistant Composites

He¹,

Begines²,

Trindade³

et al. 2020

Preprint

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<p>As our understanding of disease grows, it is becoming established that treatment needs to be personalized and targeted to the needs of the individual. In this paper we show that multi-material inkjet-based 3D printing, when backed with generative design algorithms, can bring a step change in the personalization of medical devices. We take cell-instructive materials known for their resistance to bacterial biofilm formation and reformulate for multi-material inkjet-based 3D printing. Specimens with customizable mechanical moduli are obtained without loss of their cell-instructive properties. The manufacturing is coupled to a design algorithm that takes a user-specified deformation and computes the distribution of the materials needed to meet the target under given load constraints. Optimisation led to a voxel map file defining where different materials should be placed. Manufactured products were assessed against the mechanical and cell-instructive specifications and ultimately showed how multifunctional personalization emerges from generative design driven 3D printing.</p>

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A Reactive Prodrug Ink Formulation Strategy for Inkjet 3D Printing of Controlled Release Dosage Forms and Implants

Cited by 19 publications

References 43 publications

Inkjet based 3D Printing of bespoke medical devices that resist bacterial biofilm formation

Inkjet based 3D Printing of bespoke medical devices that resist bacterial biofilm formation

Customisable Tablet Printing: The Development of Multimaterial Hot Melt Inkjet 3D Printing to Produce Complex and Personalised Dosage Forms

Exploiting Generative Design for Multi-Material Inkjet 3D Printed Cell Instructive, Bacterial Biofilm Resistant Composites

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