In vitro and in vivo studies of 3D orthopaedic implants with cell-instructive nanotopographies
Lead Research Organisation:
University of Bristol
Department Name: Oral and Dental Science
Abstract
The demand for total hip and knee replacements (THR & TKR) has been steadily increasing worldwide. This is due to an ageing population, the rise in obesity and a change to more active lifestyles; together, these factors are leading to more osteoarthritis and degeneration of cartilage and subchondral bone in joints. The two leading causes of this type of orthopaedic implant failure are loosening (due to poor bone contact with the implant) and infection (due to bacterial infiltration and biofilm formation). In the case of THR/TKR, the incidence rate of joint infections is reported to be 1%- 4% in primary surgery and up to 30% in revision surgery. Our previous work showed that certain nanostructured surfaces on titanium (many orthopaedic implants are made from titanium) surfaces could be both bactericidal and bioactive (bone forming). However, most of the work so far was carried out on nanostructured 2D surfaces rather than real implant surfaces.
This project is aimed at conducting in vitro and pre-clinical studies based on 3D porous Ti implants with nanostructured surfaces, hence translating our current understanding in 2D into real 3D implants. We have assembled a multidisciplinary team from universities of Bristol, Glasgow and Cambridge, in partnership with clinical and industrial partners, to progress our research findings from previous EPSRC projects focusing on the basic science of bactericidal topographies on 2D surfaces towards the real world applications. We will bring together expertise in biomaterials, nanotechnology, stem cell biology, microbiology and pre-clinical studies, with a clear vision to apply new smart cell-instructive surfaces to orthopaedic implants. We hope to improve the quality of life of patients who require implants and save the costs of NHS by avoiding the need for revision due to implant loosening and infection.
This project is aimed at conducting in vitro and pre-clinical studies based on 3D porous Ti implants with nanostructured surfaces, hence translating our current understanding in 2D into real 3D implants. We have assembled a multidisciplinary team from universities of Bristol, Glasgow and Cambridge, in partnership with clinical and industrial partners, to progress our research findings from previous EPSRC projects focusing on the basic science of bactericidal topographies on 2D surfaces towards the real world applications. We will bring together expertise in biomaterials, nanotechnology, stem cell biology, microbiology and pre-clinical studies, with a clear vision to apply new smart cell-instructive surfaces to orthopaedic implants. We hope to improve the quality of life of patients who require implants and save the costs of NHS by avoiding the need for revision due to implant loosening and infection.
Technical Summary
This project is aimed at conducting in vitro and in vivo studies cell/microbiological studies of 3D porous Ti implants with nanostructured surfaces; translating our current understanding of 2D nanotechnology into 3D. We have assembled a multidisciplinary team from universities of Bristol, Glasgow and Cambridge in partnership with clinical and industrial partners to address important scientific and technological questions that will permit us to progress towards preclinical/clinical trials. For example (1) do MSCs and bacterial cells respond similarly to 3D curved nanostructured Ti surfaces on porous implants as they do on 2D nanostructured surfaces? (2) do the osteogenic-antibacterial effects remain if MSCs and bacteria are cultured together on the surfaces? (3) do the nanotopographies remain cell instructive in the dynamic in vivo microenvironment? (4) can we further functionalise the nanotopographies to enhance the synergy of antibacterial properties and osteogenic potential? To this end, we will investigate two 'non-line-of-sight' nanostructuring techniques to generate nanotopographies on 3D porous Ti implants and assess their robustness under simulated surgical conditions. We will use flow-cell microbiology screening, stem cell/bacteria co-culturing and infected animal models to study their response to bacteria and/or stem cells in order to understand their interactions and optimise the cell-instructive surface nanotopographies to develop 3D smart implants for orthopaedics.
Planned Impact
The proposed project will focus on the development of smart 3D Ti implants for use in orthopaedics that are able to prevent bacterial infections while promoting osseointegration. The immediate beneficiaries will be biomedical and biomaterials researchers and then end users i.e. orthopaedic surgeons and companies who implement and make medical implants and devices. The knowledge generated in this project will broadly benefit researchers from a wide range of backgrounds of both fundamental and applied nature, including biomaterials, nanoscience and nanotechnology, microbiology, stem cell biology, biomedical engineering and orthopaedics. Anticipated benefits to orthopaedic surgeons will be improved success rate of implant surgeries using the developed products. Orthopaedic implant companies will benefit from the knowledge generated in this project to guide the rational design and manufacture of future smart implants to combat AMR infection, with long term benefits of profits, turnover and job creation. They will be closely involved in the project from the outset, providing 3D printed implant samples for testing, and advising on possible regulatory pathways during the course of the project. This means they can take our technology being developed and quickly incorporate it into their own products. Ultimately, our research will benefit those individuals requiring orthopaedic implants, including the increasingly elderly population and more active younger generation, by offering longer lasting implants without the need of revision in their lifetime. The research will also benefit the NHS that bears the costs of current ineffective treatment of infection based on antibiotics. Revision is often the only option to totally eliminate implant infection. However, infection alone in total hip replacement (THR) and total knee replacement (TKR) revision can cost £70,000 per patient to treat. Thus an implant solution that eliminates the need for revision surgery has potential to save the NHS up to £300 million per annum.
Publications
Dunseath O
(2019)
Studies of Black Diamond as an antibacterial surface for Gram Negative bacteria: the interplay between chemical and mechanical bactericidal activity.
in Scientific reports
Mas-Moruno C
(2019)
Multifunctional Coatings and Nanotopographies: Toward Cell Instructive and Antibacterial Implants.
in Advanced healthcare materials
Lu X
(2020)
The effect of Cu content on corrosion, wear and tribocorrosion resistance of Ti-Mo-Cu alloy for load-bearing bone implants
in Corrosion Science
Xu W
(2020)
Characteristics of novel Ti-10Mo-xCu alloy by powder metallurgy for potential biomedical implant applications.
in Bioactive materials
Jenkins J
(2020)
Antibacterial effects of nanopillar surfaces are mediated by cell impedance, penetration and induction of oxidative stress.
in Nature communications
Ishak M
(2020)
Protruding Nanostructured Surfaces for Antimicrobial and Osteogenic Titanium Implants
in Coatings
Srivas P
(2021)
Net shape forming of Ti6Al4V implants via green machining
in Journal of Materials Research
Ishak MI
(2021)
Insights into complex nanopillar-bacteria interactions: Roles of nanotopography and bacterial surface proteins.
in Journal of colloid and interface science
Ishak MI
(2021)
Friction at nanopillared polymer surfaces beyond Amontons' laws: Stick-slip amplitude coefficient (SSAC) and multiparametric nanotribological properties.
in Journal of colloid and interface science
Description | (Bio-TUNE) - Fine tune of cellular behavior: multifunctional materials for medical implants |
Amount | € 814,200 (EUR) |
Funding ID | 872869 |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 01/2020 |
End | 12/2023 |
Description | emPOWER: in-body artificial muscles for physical augmentation, function restoration, patient empowerment and future healthcare |
Amount | £6,142,804 (GBP) |
Funding ID | EP/T020792/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2021 |
End | 08/2026 |
Title | Materials-driven fibronectin assembly on nanoscale topography enhances mesenchymal stem cell adhesion, protecting cells from bacterial virulence factors and preventing biofilm formation |
Description | |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | http://researchdata.gla.ac.uk/id/eprint/1051 |
Description | 3D printed Ti implants |
Organisation | Renishaw PLC |
Country | United Kingdom |
Sector | Private |
PI Contribution | Provide 3D printed Ti implants for surface nanopatterning |
Collaborator Contribution | Provide samples of 3DP Ti blocks for surface patterning and microbiological testing |
Impact | Advanced manufacturing and medical devices |
Start Year | 2020 |
Description | Novel 3D Printed Ti implants |
Organisation | University of Science and Technology Beijing |
Country | China |
Sector | Academic/University |
PI Contribution | The USTB provides newly developed 3D printed Ti alloy implants for surface nanostructuring at University of Bristol. |
Collaborator Contribution | We carry out nanopatterning of Ti implants and stem cells/microbiological studies to produce cell-instructive surfaces. |
Impact | So far, 3 joint publications were obtained. |
Start Year | 2020 |
Description | Biofilm Create! Competition 2022 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | A competition organised by the National Biofilm Innovation Centre funded by the UKRI (BBSRC). |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.biofilms.ac.uk/biofilm-create-competition-2022-winners/ |
Description | FUTURES festival on 30th Sep 2022 held in SS Great Britain, Bristol |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Outreach event to showcase researches in the University |
Year(s) Of Engagement Activity | 2023 |
Description | GW4 AMR Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | >100 researchers esp. ECR attended the GW4 Alliance (Bristol, Bath, Cardiff and Exeter) organised AMR Conference. |
Year(s) Of Engagement Activity | 2021 |
Description | Invited Talk , Advanced Powder Materials Online Forum |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | An online event organised by the Central South University of China |
Year(s) Of Engagement Activity | 2022 |
Description | Invited lecture, London Interdisciplinary Biosciences Consortium, UK |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | PhD students based in BBSRC DTP in London Interdisciplinary Biosciences Consortium attended this lecture. |
Year(s) Of Engagement Activity | 2023 |
Description | Invited talk, Online forum on the Fundamentals of Composites, Zhejiang University, China |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | PhD students and other researchers attended this online event organised by Zhejiang University of China. |
Year(s) Of Engagement Activity | 2022 |
Description | Keynote lecture in International Forum and Silk Road Conference on Advanced Functional Films and Coatings, Xi'an, China |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The intended purpose of this international forum was to exchange the latest research information on surface engineering. i was invited to give a keynote lecture on our work on antimicrobial surfaces. |
Year(s) Of Engagement Activity | 2020 |
Description | Keynote lecture, International Conference on Emerging Trends of Healthcare Technology in Post-COVID-19 Era, Indian Institute of Technology, Kharagpur, India |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | An online international conference organised by IIT Kharagpur, India. The intended purpose was to report latest development in medical technology in post-COVID-19 era. I was invited to give a keynote lecture on our work on smart implants. |
Year(s) Of Engagement Activity | 2020 |
Description | National Biofilms Innovation Centre (NBIC) All Research Partner meeting |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Researchers and industrial partners to exchange information of their research under the NBIC memberships |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.biofilms.ac.uk/ |
Description | Poster presentation, Infection and Immunity Research Network Early Career Researchers' event, University of Bristol, 1st Feb 2023 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Annual event organised by the University, esp. for ECRs |
Year(s) Of Engagement Activity | 2023 |
Description | Poster presentation, The 8th Thesinge Biofilm Conference, May 23-24, 2022, The Netherlands |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | An international conference held biennially with about 200-300 participants from academia and industries. |
Year(s) Of Engagement Activity | 2022 |
URL | https://biofilm-thesinge.com/index.php |
Description | Presentation at RSC Twitter Conference |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Poster presentation to showcase our research in antimicrobial surfaces to general public. |
Year(s) Of Engagement Activity | 2021 |
Description | Presentation at UoB Infection and Immunity ECR Symposium |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | >50 researchers, mostly ECRs attended the event to exchange information in I&I theme. |
Year(s) Of Engagement Activity | 2021 |
Description | RSC Poster 2023 - Twitter Conference |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | An online conference organised by the RSC. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.rsc.org/our-events/rsc-poster/ |