Integrated Molecular Design of Melt-processable Bioresorbable Engineering Nanocomposites for Healthcare (BENcH)
Lead Research Organisation:
University of Nottingham
Department Name: Faculty of Engineering
Abstract
This proposal will deliver novel, integrated methodologies for the design and scalable manufacture of next generation resorbable polymer nanocomposites, linking the science and engineering principles which underpin successful processing of such materials. This will enable new smart health-care materials in applications from bone fracture fixation to drug delivery. The methodologies will be optimised on a system comprising novel nanoparticles, selected blends of medical-grade degradable polymer and specifically designed molecular dispersants. Optimised methodologies will be applied at scale on industrial equipment to produce demonstrator resorbable implants with specific structural attributes and degradation timescales. Wider applications include degradable food packaging and products requiring end-of-life disposal.
Planned Impact
The investigators will benefit via extension of collaborative work, improvement of facilities and a strong basis for downstream research and prestige gained through dissemination. The work would also open up opportunities for external collaboration both with academic institutions and industrial parties.
The students and researchers will benefit from extensive cross-disciplinary training and development of critical skills both in terms of laboratory capability and ability to communicate to peer and lay groups. In addition they will establish an international presence in the field, interacting with their peer groups and developing international links.
The wider academic community will benefit from gaining new understanding of nanocomposite materials, surfactants and associated methods developed during the course of the project. Collaborations developed as part of the project will help to foster links between groups and further collaborative and interdisciplinary research into associated fields such as manufacturing. The project is expected to develop from a foundation of understanding into a widely applicable field of research that will feed into new fields.
The University of Nottingham benefits directly though prestige publications on the work and the contribution to REF that will help to maintain its top 10 status.
Industrial parties linked with the project and members of the strategic advisory group will benefit through: (a) direct access to the results of the work, (b) the ability to influence the direction of the work stream, (c) the opportunity to be first to exploit the technology as it develops in the form of IP and first to market products.
Industrial parties outside of the core strategic group will also benefit from the work through knowledge transfer activities making them aware of the project and its outcomes.
Society as a whole will benefit through the availability of new material types applicable to medical use - providing improved quality of life. Extension of these materials and knowledge of their manufacture into additional fields will provide new products in different sectors (e.g. packaging), where the degradable character will offer routes to reducing waste in commodity products. Naturally derived polymers such as PLA could also help to reduce the requirements for oil in these sectors.
The economy will benefit through the development of new material types via the establishment of new companies or technology lines, providing job creation and revenue generation. The materials under investigation are a new development in a field not well understood and the UK has an opportunity to take a lead in this area. Basic materials could well be under industrial development within the duration of the project, with more advanced materials available within 5 - 10 years.
The students and researchers will benefit from extensive cross-disciplinary training and development of critical skills both in terms of laboratory capability and ability to communicate to peer and lay groups. In addition they will establish an international presence in the field, interacting with their peer groups and developing international links.
The wider academic community will benefit from gaining new understanding of nanocomposite materials, surfactants and associated methods developed during the course of the project. Collaborations developed as part of the project will help to foster links between groups and further collaborative and interdisciplinary research into associated fields such as manufacturing. The project is expected to develop from a foundation of understanding into a widely applicable field of research that will feed into new fields.
The University of Nottingham benefits directly though prestige publications on the work and the contribution to REF that will help to maintain its top 10 status.
Industrial parties linked with the project and members of the strategic advisory group will benefit through: (a) direct access to the results of the work, (b) the ability to influence the direction of the work stream, (c) the opportunity to be first to exploit the technology as it develops in the form of IP and first to market products.
Industrial parties outside of the core strategic group will also benefit from the work through knowledge transfer activities making them aware of the project and its outcomes.
Society as a whole will benefit through the availability of new material types applicable to medical use - providing improved quality of life. Extension of these materials and knowledge of their manufacture into additional fields will provide new products in different sectors (e.g. packaging), where the degradable character will offer routes to reducing waste in commodity products. Naturally derived polymers such as PLA could also help to reduce the requirements for oil in these sectors.
The economy will benefit through the development of new material types via the establishment of new companies or technology lines, providing job creation and revenue generation. The materials under investigation are a new development in a field not well understood and the UK has an opportunity to take a lead in this area. Basic materials could well be under industrial development within the duration of the project, with more advanced materials available within 5 - 10 years.
Organisations
- University of Nottingham (Lead Research Organisation)
- TESco Associates Inc (Collaboration)
- Promethean Particles Ltd (Collaboration)
- Evonik Industries (Collaboration)
- Lucite International (United Kingdom) (Project Partner)
- TESco Associates (United States) (Project Partner)
- Promethean Particles (United Kingdom) (Project Partner)
- Thermo Fisher Scientific (United Kingdom) (Project Partner)
- Evonik (Germany) (Project Partner)
Publications
Deng E
(2015)
Molecular Differentiated Initiator Reactivity in the Synthesis of Poly(caprolactone)-Based Hydrophobic Homopolymer and Amphiphilic Core Corona Star Polymers.
in Molecules (Basel, Switzerland)
De Focatiis, D.S.A.
(2015)
Production and properties of novel bioresorbable nanocomposites of PLA and nanohydroxyapatite
Atkinson R
(2021)
RAFT polymerisation of renewable terpene (meth)acrylates and the convergent synthesis of methacrylate-acrylate-methacrylate triblock copolymers
in Polymer Chemistry
Gimeno-Fabra, M.
(2015)
Research Activities at the UoN's Bioengineering Group
Alexander W
(2018)
Synthesis and control of crosslinked poly(acrylic acid) based viscosity modifiers using dense phase carbon dioxide as a solvent
in The Journal of Supercritical Fluids
Goddard AR
(2021)
Synthesis of water-soluble surfactants using catalysed condensation polymerisation in green reaction media.
in Polymer chemistry
Nguyen N
(2014)
Understanding the acceleration in the ring-opening of lactones delivered by microwave heating
in Tetrahedron
Description | New dispersants have been successful designed for the target composites and these have been successfully attached to the target nanoparticle platelets. A method for continuous manufacturing the coated nanoparticles has been developed and is now being used to scale up the production to allow trials of the full composite materials to be conducted with the industrial sponsors. The dispersant coated nanoparticle have been successfully extrusion compounded into matrix polymers at several levels and the properties have been assessed and compared to both matrix polymer and composites made with nanoparticles that do not contain dispersant. Some processing issues were discovered with the best performing dispersant systems due to their high level of interfacial activity. This has been mitigated by developing a method a method to purify and partially mix the nanoparticles in matrix polymer prior to extrusion using supercritical carbon dioxide as a processing medium 2017). Additionally the un-coated particles have been shown to exhibit aggregation during freeze drying which mitigated by the addition of the dispersant. This is being further investigated as a further process benefit of the project work (2018 and 2019). This has lead to a successful full scale production trail being run at the TESco Associates site in Boston. This has only been partially completed due to Covid issues. Material from this trial has just been received at the University of Nottingham for further testing which has been postponed due to Corvid access issues to the appropriate laboratories. One of the key outcome from the first section of the trial as the dried nanoparticle seem to produce important benefits with respect to the levels of polymer degradation observed during processing |
Exploitation Route | The continuous manufacture of dispersant coated nanoparticles is of great interest and utility to many materials market sectors / academic groups. The purification / premixing of nanoparticles using supercritical carbon dioxide may allow other groups to overcome toxicological issue with other systems. Further research is needed on the methods of isolating nano-partials and this has proven to be more problematic at scale. However the dispersant costing prove to overcome this issue to a considerable extent. There is interest in adding BENcH nanoparticles to the polymer just for the potential improvements that are observed during polymer processing of the polymer alone |
Sectors | Aerospace Defence and Marine Chemicals Electronics Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
Description | One of the industrial funders is in the process of investigating the potential to use the BENcH dispersants to as additive coatings in of a second set of bio-materials which do not include hydroxyapatite (started 2017 - ongoing). Additionally a trial in planned for use of the HA particles on their full scale manufacturing assets (2018). This has lead in 2020 to TESco associates planning to conduct a full scale production run with the treated nano-particles supplied by the University of Nottingham team and Promethean Particles. This trial followed a extensive set of clearance pre-work to enable the particles to be used safely at the manufacturers site. This was additionally complicated by the fact that they pre-part medical products and so all the effects on the potential subsequent production on the equipment used had to be evaluated. This also involved pre-compounding trials which have been delayed due to Covid Lockdowns but positive new influences of adding BENcH nanoparticles have been observed in relation to processing these medical polymers during these trials. These observation will be supported by further materials analysis at Nottingham on the laboratories and have lead to the reopening of discussions on IP filing and further support for this type of work. |
Sector | Chemicals,Healthcare |
Impact Types | Economic |
Description | IP discussion for filing a patent on the outcomes of the Covid Delayed company trial is ongoing |
Geographic Reach | North America |
Policy Influence Type | Influenced training of practitioners or researchers |
Description | Advanced Manufacturing of Polymers (AdMaP) |
Amount | £618,614 (GBP) |
Funding ID | Project Number 8924 - Advanced Manufacturing of Polymers (AdMaP) |
Organisation | Innovate UK |
Sector | Public |
Country | United Kingdom |
Start | 11/2021 |
End | 12/2021 |
Description | ENGINEERING SUSTAINABLE SQUALENE ANALOGUES FOR NOVEL VACCINE ADJUVANT EMULSIONS |
Amount | $2,511,203 (USD) |
Funding ID | R01AI135673 |
Organisation | National Institute of Allergy and Infectious Diseases (NIAID) |
Sector | Public |
Country | United States |
Start | 01/2018 |
End | 12/2022 |
Description | EPSRC Impact Accelerator |
Amount | £81,940 (GBP) |
Funding ID | EP/K503800/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 02/2014 |
End | 09/2015 |
Description | Hermes Fellowship |
Amount | £31,500 (GBP) |
Organisation | University of Nottingham |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2017 |
End | 07/2017 |
Description | Polymerisation method development for the manufacturing of novel, high-performance, compostable and recyclable hetero-aromatic bioplastics for the packaging industry (BioPolyMet) |
Amount | £272,971 (GBP) |
Funding ID | Project Number 50994 |
Organisation | Innovate UK |
Sector | Public |
Country | United Kingdom |
Start | 09/2020 |
End | 04/2022 |
Title | Addition of super dried nanomaterials to degradable polymers to improve polymer process t full compounding scale |
Description | The addition of the dried nanomaterials can reduce the negative effects observed on the polymer during full scale compounding processing |
Type Of Material | Technology assay or reagent |
Year Produced | 2020 |
Provided To Others? | No |
Impact | There is an ongoing discussion with collaborator about the potential to file intellectual property in this area. |
Description | Funding of Hermes Grant by Evonik |
Organisation | Evonik Industries |
Country | Germany |
Sector | Private |
PI Contribution | The partner are providing an additional 300 GBP to fund the Hermes fellowship and will also be introducing funding via work in-kind to compound the materials made by Nottingham into final articles |
Collaborator Contribution | This follow on project from the work which has followed on from the work conducted in the BENcH Grant, Evonik will be supplying polymer to this project |
Impact | Evonik have allowed the BENcH group to pre-process materials at their site during 2016 |
Start Year | 2013 |
Description | Funding of Hermes Grant by TESco Associate |
Organisation | TESco Associates Inc |
Country | United States |
Sector | Private |
PI Contribution | We care preparing material to be sent to trail work at Tesco Associates site |
Collaborator Contribution | The partner are providing an additional 300 GBP to fund the Hermes fellowship and will also be introducing funding via work in-kind to compound the materials made by Nottingham into final articles |
Impact | This follow on project from the work which has followed on from the work conducted in the BENcH Grant |
Start Year | 2013 |
Description | Scale up manufacture of the uncoated and coated nanoparticles achieved |
Organisation | Promethean Particles Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | The dispersal polymer was synthesized and characterized in sufficient quality for the scale up strategy agreed with Promethean Particles (PP) within the University of Nottingham Laboratories. This was passed on the PP who attempted to synthesized the coated and un-coated particles samples that were agreed for the trial at TESco Associates. However difficulties were encountered with the scale up of both of these materials. a) Coated Particles - This needed very large volumes of solvent to be used to manufacture these so a smaller amount of these were made as, to make the required amount, would have required too much in the form of Freeze drying costs. (b) Un-coated particles - greater levels of aggregation were observed with these materials during freeze drying. These materials were freeze dried by a toll processing company. The un-coated materials have been dispatched to and received by TESco a trial is planned with the these material both dried and non-dried after the Easter period. |
Collaborator Contribution | See the paragraph above for the part played by Promethean Particles |
Impact | These materials have been provided for a trial that will be held in the future so there has been no impact as yet. |
Start Year | 2013 |
Description | Scale up manufacture of the uncoated and coated nanoparticles achieved |
Organisation | Promethean Particles Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | The dispersal polymer was synthesized and characterized in sufficient quality for the scale up strategy agreed with Promethean Particles (PP) within the University of Nottingham Laboratories. This was passed on the PP who attempted to synthesized the coated and un-coated particles samples that were agreed for the trial at TESco Associates. However difficulties were encountered with the scale up of both of these materials. a) Coated Particles - This needed very large volumes of solvent to be used to manufacture these so a smaller amount of these were made as, to make the required amount, would have required too much in the form of Freeze drying costs. (b) Un-coated particles - greater levels of aggregation were observed with these materials during freeze drying. These materials were freeze dried by a toll processing company. The un-coated materials have been dispatched to and received by TESco a trial is planned with the these material both dried and non-dried after the Easter period. |
Collaborator Contribution | See the paragraph above for the part played by Promethean Particles |
Impact | These materials have been provided for a trial that will be held in the future so there has been no impact as yet. |
Start Year | 2013 |
Description | Trail of composite materials in Company trial |
Organisation | TESco Associates Inc |
Country | United States |
Sector | Private |
PI Contribution | Trail was successfully completed and University of Nottingham materials performed very well. We prepared the martials and sent them to TESco for evaluation |
Collaborator Contribution | They stopped production for a period of time to process out materials into medical device |
Impact | We are now in discussion with the company sponsor about the potential IP protection of the methods to make these materials and there use in a limited section of the medical device market |
Start Year | 2012 |
Description | Trail of composite materials in Company trial |
Organisation | TESco Associates Inc |
Country | United States |
Sector | Private |
PI Contribution | Trail was successfully completed and University of Nottingham materials performed very well. We prepared the martials and sent them to TESco for evaluation |
Collaborator Contribution | They stopped production for a period of time to process out materials into medical device |
Impact | We are now in discussion with the company sponsor about the potential IP protection of the methods to make these materials and there use in a limited section of the medical device market |
Start Year | 2013 |
Description | Trial production of medical grade polymer composites by TESco Associates |
Organisation | TESco Associates Inc |
Country | United States |
Sector | Private |
PI Contribution | TESco associates have conducted a full scale production run with the treated nano-particles supplied by the University of Nottingham team and Promethean Particles. This trial followed a extensive set of clearance prework to enable the particles to be used safely at the manufacturers site. This was additionally complicated by the fact that they pre-part medical products and so all the effects on the potential subsequent production on the equipment used had to be evaluated. This also invovled pre-compounding trials These particles included materials, in various device forms, have been resumed the the University of Nottingham where they will undergo a series of material property test over summer with a placement researcher. |
Collaborator Contribution | Our collaborators (Tesco Associates) have taken kilogramme quantities of our treated nano-particles and have conducted a full scale production run This trial followed a extensive set of clearance pre-work which included Full HAZOP safety review Bio review of potential effects on the ability of the apparatus used to ensure that subsequent batches would not be effects Pre-compounding trials Full scale manufacture of 3 difference device types. |
Impact | Materials have been sent back to Nottingham for material property testing to review the effect on process properties due to the inclusion of the nano-particles This data will be shared with TESco associates, who, in turn, will provide a view on their estimated of the difference in processing conditions relative to the standard materials that they manufacture with on a commercial basis. |
Start Year | 2020 |
Description | Trial still to be conducted as this was postponed due to Covid Restrictions within the Collaborator and University sites |
Organisation | TESco Associates Inc |
Country | United States |
Sector | Private |
PI Contribution | We sent materials to TESco for compounding |
Collaborator Contribution | The compounded our materials and returned mateiasl to us for further testing |
Impact | Fully compounded research materials |
Start Year | 2013 |
Title | Trail of medical device material was completed after COVID delay |
Description | The trailing of the project materials has realised a further discussion with one of the project sponsor on IP generation and routes to further support the development |
Type | Therapeutic Intervention - Medical Devices |
Current Stage Of Development | Initial development |
Year Development Stage Completed | 2021 |
Development Status | Actively seeking support |
Impact | This has lead to a potential for IP development |
Description | Impact paper in "Medical Plastic News" |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | This was an article detailing the work conducted in the grant and within the group in the area of resorbable materials processing |
Year(s) Of Engagement Activity | 2015 |
Description | Presentation at Warwick 2106 Internation conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Conference presentation |
Year(s) Of Engagement Activity | 2016 |
Description | Presented a Exhibirtion Stand at the Royal Society Summer Exhibition |
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 | The exhibition stand was in operation for 5 days during the summer exhibition including 2 evening session for policymakers and professional practitioners |
Year(s) Of Engagement Activity | 2016 |
Description | Radio Broadcast by Dr D Focatiis on Bench |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | This was a radio broadcast that supported the Summer Exhibition link to further publicise it |
Year(s) Of Engagement Activity | 2016 |