In-Silico Modelling and 3D-printing of Dental Implants with Photo-active and Infection-Resistant Coatings (PERIo-Dent-ItiS)

Lead Research Organisation: University of Leeds
Department Name: Chemical and Process Engineering

Abstract

Peri-implantitis is an infection-related condition around the implant, which occurs because of inflammation arising from the acidic interstitial fluid, produced by the presence of bacteria in the biofilm. The biofilms form on the peripheral surface of implants. The acid slowly resorbs the healthy bones, enervates soft-tissue anchorage, loosens the implant, and causes pain. Loss of mechanical support also aggravates the pain and, therefore, compromises the chewing and mastication which are essential for the easier digestion of food. Although, the success rate of implants is 85-90%, however, 10-15% implants fail during lifetime because of the lack of early diagnosis. The diagnosis of failed implants is poor and only when the pain is felt, the patients are prescribed pain killers, monitored before the surgical intervention removes the implant.

Innovative Vision: With increasing 50+-years age group needing more implants, there is an urgent need for improving the implants for better osseointegration for preventing mechanical failure. Our goal is to provide infection resistance against bacteria and to design means for ascertaining early signs of biofilm formation. During secondment at Attenborough Dental (AD) in Nottingham, the secondee will use the 3D-printing and Additive Manufacturing facility for fabricating implants for promoting the formation of a strong hard-soft tissue anchorage, and vascularization which will intrinsically prevent the risk of infection from bacteria. The materials patented (PCT/GB2015/052557) at the University of Leeds will form the basis for developing new generations of infection-resistant and photo-responsive implants for the early signs of detection of infection.

Objectives: The four objectives are: O.1) to demonstrate in silico and biomechanical modelling approach for the fabrication of standard implants with infection-resistance and photo-responsive coatings, designed from calcium phosphate with CeSr-oxide (CeSrOx)/chitosan as the antibacterial and Europium-Samarium oxide (EuSMOx) as photo-responsive coating, respectively.

O.2) We will adopt the steps in O.1 and demonstrate the fabrication of porous Ti-implants for improved micro-fluidics and osseointegration with infection resistance and photo-responsive features for non-invasive diagnostics. The porosity control for microfluidic properties is essential for infection control, improved vascularization, and strong tissue anchorage.

O.3) The UoL-AD team will review in silico and biocompatible modelling for design and fabrication of route analogues using 3D-AM with the porous Ti-alloy structure. Such a new design offers one-step surgery for improved osseointegration, infection resistance (CeSrOx), and methods for monitoring healing by interrogating the photo-active EuSmOx layer.

O.4) We will focus on microstructural and physical characterizations, stress analysis, bio-compatibility (toxicity, attachment, proliferation), osteogenesis and angiogenesis, and photo-active response in cellular and simulated oral fluid condition of implant materials which will be essential for future animal studies.

Secondee: A full-time secondment will fulfil the goals of each objective. The secondment will develop the digital imaging approach for controlling the porosity and bio-mechanical stress using 3D-printing and additive manufacturing facility at AD. The manufacturing of implants with the standard Ti-alloy powder, CeSrOx and EuSmOx mixed with calcium phosphate will be demonstrated, and the properties of implants will be characterized using the state-of-the-art analytical and modelling facilities at AD and UoL. The results of fabrication and characterization will be used for ascertaining the longevity of implants in the oral environment under acidic condition. The training will also aim towards developing business-relevant skills. Important non-confidential results will be published in the peer-reviewed journal, after securing the patent position.

Technical Summary

The proposed secondment is a collaboration between the University of Leeds and Attenborough Dental (AD) in Nottingham. AD aims to demonstrate a novel 3D-printing and additive manufacturing process for new generations of dental implants. These implants are targeted to minimize the risk of infection, which causes the peri-implantitis, which is often observed in 10-15% of patients with implants. In the case of peri-implantitis, the implants fail due to loosening. The symptom also occurs in combination with the prevalent bacterial infection around the implant surface where the acidic fluid slowly resorbs healthy bone. The bone resorption may accelerate under the chewing and mastication. Currently, there is no long-term solution for early detection of the onset of bacterial infection until the pain starts, which implies that the infection has spread and surgical intervention might be necessary, depending on the acuteness of peri-implantitis.

The number of cases of peri-implantitis is rising at 6% per annum in the 50+ years age group. A solution must be found which must be able to minimize the risk of peri-implantitis by improving the implant design.
The industrial secondment at AD aims to demonstrate a new paradigm in implant manufacturing by transferring the knowledge from UoL and by building a co-creation approach for manufacturing via research in the following areas:

a) by providing CAD implant design which will be porous instead of solid Ti-alloy. Novel design will offer a much better opportunity for implant-tissue integration;

b) by designing biomechanically robust implant which in the oral acid condition does not fail and curtails bacterial infection; and

c) by forming infection resistant film on the implant which protects against bacterial infection, and allows blood vessels to grow inside and around the porous implant for minimizing infection.
AD will benefit from knowledge exchange during the secondment by training a person for industry.
 
Description BoNE-GraFT EU Fellowship 
Organisation Leeds General Infirmary
Country United Kingdom 
Sector Hospitals 
PI Contribution Leeds General Infirmary (Prof. P. Giannoudis) LIRMM (Dr. Elena Jones) New collaboration
Collaborator Contribution The project aims to develop a strong cortical bone templates for integrative manufacturing of bone tissues.
Impact New collaboration
Start Year 2017
 
Description DTC Collaborative PhD Studentship 
Organisation Leeds General Infirmary
Country United Kingdom 
Sector Hospitals 
PI Contribution A collaborative partnership for research on physiological engineering of bone has been supported by the University with the LIRMM and LGI. Ms Neelam Iqbal is a new CASE PhD student.
Collaborator Contribution The orthopaedic tissue testing and imaging facilities are located at LIRMM and LGI, which will be utilized in the project for ascertaining the injury. Prof. Peter V Giannoudis is the main clinical supervisor who works closely with a bone biologist (Dr Elena Jones). The supervision in the area of physiological engineering of bone will involve imaging, prototyping the structure of tissue and then fabrication for designing bone which will be testing in a small animal model.
Impact The PhD student is writing her first paper at present on laser-chitosan mineral interaction.
Start Year 2016
 
Description ISMARD-EU Project (H-2020) 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution University of Manchester
Collaborator Contribution Complementary research skills
Impact a) Joint EU project workshop in Thessaloniki, Greece b) Multidisciplinary approach for the analysis of Peri-implantitis
Start Year 2021
 
Description Leitat Animal Trials 
Organisation Leitat Technological Centre
Country Spain 
Sector Charity/Non Profit 
PI Contribution The MRC-CiC project Animal studies have been facilitated at Leitat Technology Centre. The study will complete by early summer 2023.
Collaborator Contribution The contract was drawn for the animal studies and the results from the medical device trials will be available in late Spring 2023.
Impact No results are available yet, however we think the following outputs are likely: a) results from animal studies, showing the efficacy of the trials b) technology positioning document and future potential IP c) future collaboration on larger trials which saves animal lives by developing technology
Start Year 2020
 
Description MRC-CiC 
Organisation University of Leeds
Department Faculty of Medicine and Health
Country United Kingdom 
Sector Academic/University 
PI Contribution long bone materials manufacturing and animal trials
Collaborator Contribution Surgical technologies and biomechanics of long bone
Impact Not yet
Start Year 2016
 
Description Royal Commission of 1851 Industrial Fellowship 
Organisation University of Leeds
Department Leeds Institute of Rheumatic and Musculoskeletal Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution The project partnership is for physiological engineering of load-bearing (long) bones and its biomechanics. A new integrative manufacturing apporach is developed for long bones for finding a synthetic bone substitute that is compatible with the human and mamallian physiology.
Collaborator Contribution Contributions are in the area of novel surgical technologies
Impact Not available
Start Year 2015
 
Description SBR-EU project 
Organisation University of Patras
Country Greece 
Sector Academic/University 
PI Contribution This collaboration is a part of the new EU project on Stimulated Bone Regeneration which started in Jan 2020. This is a multi-partner (10 partner) research consortium on restoring large bone defects.
Collaborator Contribution Partners are expected to provide: a) Specification on bone materials fabrication b) pharmacology c) biomechanics
Impact Not yet
Start Year 2020