3Dprinted osmotic devices for the delivery of cells, drugs and vaccines
Lead Research Organisation:
Heriot-Watt University
Department Name: Sch of Engineering and Physical Science
Abstract
This is a PhD research project in Chemical Engineering. The project aims to combine newly synthesised polymeric biomaterials and the stereolithographic 3D printing technique to develop implantable delivery devices with delay times of 1 day up to several months. The device is engineered to deliver its complete payload at once, making it suitable for vaccination boosters, specific drug treatments or cell therapies.
The student has developed a photo-curable, biodegradable, tough elastomeric polymer that has been characterised thoroughly (thermomechanical properties, curing kinetics, rheometry) and can be processed both by (automated) dip coating and stereolithography printing. In the final year he is going to prepare tubes using these manufacturing techniques, and subject these to 1) burst pressure tests using a universal tensile tester and custom-made rig, and 2) in vitro delayed burst release tests, monitoring water uptake by weight and immediateness of the release of a dye by spectrophotometry.
The student has developed a photo-curable, biodegradable, tough elastomeric polymer that has been characterised thoroughly (thermomechanical properties, curing kinetics, rheometry) and can be processed both by (automated) dip coating and stereolithography printing. In the final year he is going to prepare tubes using these manufacturing techniques, and subject these to 1) burst pressure tests using a universal tensile tester and custom-made rig, and 2) in vitro delayed burst release tests, monitoring water uptake by weight and immediateness of the release of a dye by spectrophotometry.
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509474/1 | 01/10/2016 | 30/09/2021 | |||
| 1813148 | Studentship | EP/N509474/1 | 01/10/2016 | 31/03/2020 | Kerr Samson |
| Description | We have developed a tough, bioresorbable and seemingly biocompatible 3D printing (stereolithography) resin which may be useful in many medical areas including implantable medical device manufacture, like the device we are trying to develop. This resin offers mechanical properties unlike any current product in the literature or available commercially. Previous printing of our main component material (polycaprolactone) using stereolithograhy printing required it to be performed in a melted state, requiring 70+ degrees of heat. We use a friendly solvent called benzyl alcohol to dissolve our materials in, which is safe and suitable for use with the printing technology, as well as being generally regarded as possessing low toxicity in humans. This allows us to print at room temperature with budget 3D printers. Unfortunately, the material we've produced is so tough that it likely will not give our device the burst profile we hypothesise that we require. Therefore we are switching focus to developing a more elastomeric material to manufacture our device from. Update Feb 2020: From mechanical and osmotic burst tests our elastic photo-curable material improves upon the thermoplastic PCL devices made back in the device proof of concept publication. At burst, our tubes release significantly larger quantities of dye due to its elastic response. And over the course of the experiment released more dye overall. This indicates that we are on the right track with elastic materials. To improve further, we think that moving to a photo-curable copolymer material will enable us to release even more payload at the point of burst. Future work as the SAVE project will continue to develop and characterise the new copolymer and devices. Update March 2021: Following finishing my thesis and final viva, we have made efforts to take data or direction from my PhD work and turn some of it into publications. A journal article regarding the osmotic burst studies for the vaccine delivery devices made from our noval crosslinked PCL material is currently accepted pending minor revisions. We aim to get at least one journal paper published focusing on the novel materials themselves, and their potential use in stereolithography 3D printing for biomedical purposes. Next stage of work towards improving the vaccine delivery devices using a more elastic material is currently underway. Although this is funded under a different project grant/and funder from this initial work. This continuation of the topic of study also hopes to perform more toxicity testing on the materials and the devices too. Work was postponed due to the global pandemic (COVID 19) that shut laboratories between March - July 2019, and had further actute effects on lab work since then. |
| Exploitation Route | These resins/materials may be useful across a range of biomedical uses and perhaps beyond. UV-curable biocompatible resins with ranges of mechanical properties could be used to make a range of medical implant structures of various natures, drug delivery devices, or even wound protecting films on the skins surface. For the SAVE vaccine delivery project, based on the evidence generated by this PhD project, further development of elastic photocurable polymer systems will be continued. |
| Sectors | Agriculture, Food and Drink,Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | The John Moyes Lessells Travel Scholarship |
| Amount | £4,650 (GBP) |
| Organisation | Royal Society of Edinburgh (RSE) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2018 |
| End | 03/2019 |
| Title | Automated dip coating apparatus |
| Description | I designed and built an automated dip coater, which we used to produce the tubular barrel sections of the osmotic vaccine delivery devices. The machine is controlled by an Arduino, and allows adjustment of the key parameters for dip coating of steel rods to produce polymer tubes with homogeneous wall thicknesses. Different instructions can be given to the machine using G-code (a common engineering coding language often used for CNC tools or 3D printers) directly from a PC (via USB) or by an SD card. There is a small screen that allows users to navigate menus using a rotary dial, and the user can pick the instruction file to use and execute the dip coating procedure directly on the machine. The machine has the capacity to dip up to 10 individual rods at the same time. A UV light setup has been wired up to allow dip coating of photo-curable polymer solutions, which can also be controlled as part of the automation instruction set. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2019 |
| Provided To Others? | No |
| Impact | We have been using this machine to make tubes for prototype vaccine delivery devices of various different polymer solutions since its construction. |
| Description | QUT: Tim Dargaville |
| Organisation | Queensland University of Technology (QUT) |
| Department | Institute of Health & Biomedical Innovation |
| Country | Australia |
| Sector | Academic/University |
| PI Contribution | I bring knowledge of material development and characterisation, polymer synthesis, stereolithography printing and phamacological knowledge to this partnership. Both teams are working on very similar projects with shared goals and problems to overcome. The original concept was borne out of a collaboration between my supervisor (Ferry Melchels) and Tim Dargaville back in 2015. I part was to reignite this collaboration, and force connections for myself, that will better my contribution to the project as well as for the future of the project. |
| Collaborator Contribution | My collaborators provided modern and well equipped facilities for us to conduct our work together, as well as important knowledge on biomaterial cytotoxicity testing, aspects of polymer synthesis that I am weak on, as well as equipment and knowledge regarding dip coating technologies to manufacture tubular structures. |
| Impact | This project is highly multi-disiplinary, drawing on engineering, biology, and chemistry. The collaboration helped: - Optimise synthesis and purification of my materials (chemistry/polymer chemistry) - Mechanical testing of my materials (engineering) - Production of devices constructed out on my materials (engineering/polymer chemistry) - Cytotoxicity assessments of my materials on primary dermal fibroblasts (biology) It is hoped we can publish jointly regarding some of my work there, but this requires further research together to generate the required data to move towards submission of a publication. |
| Start Year | 2018 |
| Description | DIS Scandinavian Study abroad lab tour |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Undergraduate students |
| Results and Impact | A cohort of American biotech students on a Scandinavian Study Abroad programme visited our University. As part of their visit, I gave them a lab tour of our facilities, and spoke to them about my and the groups research. A demonstration of our stereolithography printers, resins and printed products. The students asked questions throughout, which ranged from direct scientific intrigue about the project, general opinions on studying in the UK, and guidance on further study and PhD opportunities. These students already study within a relevant field, but allowed them to experience another research environment and engage with active researchers, which may help them choose their own path when they finish their own degree programmes. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Edinburgh Science Festival: Family Fun Day at Oriam (Heriot Watt University) |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | This event was part of the Edinburgh Science Festival in April 2019. The event at Heriot Watt University was conducted at the sports centre, Oriam. The event was aimed at young children, approximately primary school age and under. Children recieved "Discovery Passports" to collect stickers and facts during their day. Our department had their own exhibit, which ran all day. The exhibit was centred around the development of drugs from disease to treatments, and highlighted some of the areas of research being conducted without our department. I did a specific talk and demonstration on the different ways we can deliver drugs. I showed examples of paracetamol tablets, powder-filled capsules, syrups (like calpol), and infusion pumps. To demonstrate how different release of drugs work, I used a food dye to produce vivid colour changes within conical flasks. As my PhD is regarding development of a delayed release device, I pre-prepared sponges with a depot injection of dye within them. When added to the water, the dye is kept within the sponge and slowly perfuses out after a brief delay, mimicing a delayed release response. This was compared to an injection of dye from a syringe, and infusion style slow constant injection of dye from a syringe driver pump, and other methods. The kids overall were very interested, and asked good questions. They really liked the clear colour changes and it was really easy to see the "wispy" diffusion of dye from the sponge. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Heriot-Watt University: 3 minute thesis competition |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | The 3 minute thesis concept promotes consise but accessible presentation of research to wide audiences. I presented a short overview of the project and our most recent work to an international audience (Heriot-Watt has campuses in Dubai and Malaysia). The presentation was livestreamed to the university's other campuses around the world, while also recorded. Audience members included public, students of all stages, and academics. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Prepared an exhibit for a science centre in the Netherlands |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | 3D printed a nose shaped tissue scaffold for display as part of a humanoid exhibit at the Mueseon science centre in The Hague (NL). |
| Year(s) Of Engagement Activity | 2016 |
| Description | Visit by a high school and a primary school student, both interested in 3D printing |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Two friends got in contact with the Head of Insitute wanting to visit to see our 3D printers, as they had a more basic FDM printer at home and were highly enthusiastic. They visited other labs during the day visit too. In the morning they were in my lab, where I showed them our 3 stereolithography printers and explained how they worked and the differences between these and the FDM printer that they owned. I then got them to pick some models, which I printed for them while they were away visiting other labs. They returned to watch the print complete, and I removed the supports, rinsed/dried the models before giving them to the children. The eldest wants to work developing 3D printers when he is older. We were informed after the event that they have the printed models on their windowsill on display. |
| Year(s) Of Engagement Activity | 2019 |