Automated Patterning of Bioactive Deposits on Advanced Biomaterials for Orthopaedic Applications

Lead Research Organisation: University College London


Template-assisted electrohydrodynamic atomisation (TAEA) spray-patterning is a novel, recently patented, method which allows the production of interlocked bioactive coatings on flat metallic substrates. The pattern geometry can be varied by simply changing the template geometry and dimensions. The process is based on stable jetting of a flowing liquid/suspension subjected to an electric field and is carried out at the ambient temperature and pressure. It is easy to control this rapid process using the applied voltage, the flow rate and the working (collection) distance between the flow nozzle and the substrate. Because of the interlocking of the bioactive coating with a patterned buffer layer coating, previously deposited via TAEA, this method of bioactive patterning also allows better adhesion of the coating. Also, the biological response to TAEA patterned bioactive deposits by cellular entities has proven to be more favourable. These factors compare very favourably when considering the fact that conventional plasma spraying, which is usually used to just plainly cover-coat bioactive materials on metallic substrates, is carried out at extremely high temperatures (about three orders of magnitude higher) and is difficult to control especially when it comes to the preparation of thin coatings. According to industry sources, economic loss due to malfunction and shutdown time involved with plasma spraying is very significant and the industry is looking to uncover and implement alternatives. This project proposed is concerned with investigating the use of TAEA bioactive patterning on curved surfaces in order that the process is ideal for the preparation of clinical inserts and implants, especially for the orthopaedics sector which is the business of the industrial project partner. This will ensure that the process can be implemented in many real implants which have both flat and curved surfaces. The project work endeavours to systematically investigate TAEA spraying of bioactive nanostructured hydroxyapatite onto curved biometallic substrates, such as orthopaedic titanium alloys, starting from well-characterised suspensions and solutions - the viscosity, surface tension and electrical conductivity of which affect stable jetting. Convex and concave titanium alloy substrates of different diameter will be prepared, together with a variety of fitting curved copper mesh-templates which allow different patterns to be deposited - lined, hexagonal and square. One key difference between flat and curved surface TAEA will be the varying working distance encountered as spraying takes place. This can result in uneven coating thicknesses and inhomogeneties. In order to counteract this, an automated conveyer system which will enable the substrate to be held and moved in and out and/or rotated will be put in place, and the design, construction and implementation of this strategy will be a key part of the project. The microstructures of the curved surface TAEA coatings produced will be studied mainly by electron microscopy. Adhesion and mechanical properties of the coatings will be fully assessed using scratch- and nano-indentation techniques; evaluating adhesion, hardness/scratch hardness and the generation of load-displacement data from which the elastic modulus and the yield strength will be estimated. An attempt will also be made to calculate fracture toughness and residual stresses using any indentation cracks which might be present on the coatings. The coatings will also be subjected to cell culture tests in order to ascertain bioactivity. Two other aspects will also be investigated: Firstly, using an improved and simpler on-line heat treatment to consolidate the titania buffer layer on the substrate will be tried out. Secondly, we shall attempt to do co-axial (co-flow) TAEA which will pave the way for composite polymer-ceramic bioactive deposits or bioactive deposits doped with other ingredients like antibiotics and growth factors.

Planned Impact

As aging populations are growing globally, the demand for orthopaedic implants and the longevity and effectiveness required of them are also increasing. The ability to create patterns on the implant, rather than continuous coatings, assist tissue regeneration, cell orientation and attachment, and thereby the long term effectiveness of therapy. The current industry standard for manufacturing these coatings is vacuum plasma spraying (VPS) which is capable of producing adequate continuous coatings commercially, but there are several inherent limitations that prevent further optimisation. The high temperatures (~15,000C) and the vacuum environment required, mean that biological agents such as growth factors and antibiotics cannot be incorporated into the coating as it is being manufactured. VPS coatings are also not patterned, thus limiting their effectiveness. The process is energy intensive with high equipment and operational costs. Circumventing these issues could greatly improve the functionality, cost and service life of therapy. There is potential for template assisted electrohydrodynamic atomisation (TAEA) spraying to be a novel ambient temperature patterning technique, and an improved coating method compared to the current industry standard of VPS. TAEA is our patented process currently verified on flat titanium surfaces. The reduction in process operating temperature results in an increase in the range of coating materials (such as polymers) and the ability to incorporate biological agents during manufacturing. This highly controllable process could produce coatings with an ideal thickness, improved uniformity and homogeneity, and improved bond strength. A wide variety of predetermined topographical geometries can also be achieved with a high degree of control. In terms of biological response, printing patterns with topography can be much more effective than depositing a continuous coating. The simple set up and lower energy requirements result in a larger commercially viable batch size and reduced lead time. These improvements would make therapy, e.g. hip replacement, more affordable and available to more people. By providing more functionally-effective inserts and implants, it will also reduce the number of people that undergo revision surgeries. Improving the quality of therapeutic replacements would increase their effectiveness, reducing pain and improving mobility. This will enhance the quality of life of the increasing number of people that have, for example, hip replacements globally each year.


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Nithyanandan A (2015) Bioinspired electrohydrodynamic ceramic patterning of curved metallic substrates in Bioinspired, Biomimetic and Nanobiomaterials

Description How to pattern curved surfaces of biomaterials with bioactive substances and how to automate this process, including flat surfaces.
The grant activities are still in progress but has already generated industrial interest and commercial exploitation. Patents are granted in Europe, USA, China etc.
The worked has enabled the use of PEEK in this type of work and a paper has just been accepted for publication in J. Royal Society Interface, entitled "PEEK surface modification by fast ambient-temperature sulfonation for bone implant applications". THE PEEK work has been completed and is being assessed for publication.
Exploitation Route By industry, to create coatings of bioactive materials for orthopaedic and other biomedical engineering applications. The new patented patterning method is broadly applicable to any other engineering sector.
Together with UCL-Business, Orthopaedic Research UK the findings are patented (granted patents now) and with JRI Orthopaedics Ltd. and TWI we are taking matters to possible commercial fruition (most recent discussions in 2018).
Exploitation of PEEK in orthopaedics - see mention added above (i.e. recent paper in J.Roy.Soc.Interface)
Sectors Aerospace, Defence and Marine,Chemicals,Creative Economy,Digital/Communication/Information Technologies (including Software),Education,Energy,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

Description University-Industry-Medical Charity interactions. JRI Orthopaedics Ltd and Orthopaedic Research UK are very keen to exploit this research, a meeting of these communities was held on 6th January 2016 to further this collaboration. Meetings with JRI Ortopaedics Ltd. at their site in Sheffield and here in UCL have continued to further the work/commercial possibilities, a new partner, TWI, has also joined to take matters further to Innovate UK. We have also taken matters abroad, through The Royal Society London UK support we have collaborated with Sri Lanka to trial their bioactive materials with our process (Template-assisted Electrohydrodynamic Atomisation (TAEA) patterning). Promising results were achieved and the collaboration continues. Another PhD student (privately funded) has translated this technology to the deposition of bioactive materials on PEEK substrates and also automated the process. The PEEK work has made progress scientifically and a full paper on its exploitation has just been accepted by the J.Royal Soc. Interface, the abstract of which is reproduced below: "We develop a simple, fast, and economical surface treatment under ambient temperature to improve hydrophilicity and osteoconductivity of polyetheretherketone (PEEK) for bone implant applications. A major challenge in bone implants is the drastic difference in stiffness between traditional implant materials (such as titanium and stainless steel) and human bone. PEEK is biocompatible with an elastic modulus closely matching that of the human bone, making it a highly attractive alternative. However, its bio-inert and poorly hydrophilic surface presents a serious challenge for osseointegration. Sulfonation can improve hydrophilicity and introduce bioactive sulfonate groups, but PEEK sulfonation has traditionally been applied for fuel cells, employing elevated temperatures and long reaction time to re-cast PEEK into sulfonated films. Little research has systematically studied PEEK surface modification by short-reaction-time (seconds) and ambient-temperature sulfonation for biomedical applications. Here we investigate three ambient-temperature sulfonation treatments under varying reaction times (5 - 90s) and evaluate the hydrophilicity and morphology of 15 modified PEEK surfaces. We establish an optimal treatment using 30s H2SO4 followed by 20s rinsing, and then 20s immersion in NaOH followed by 20s rinsing. This 30s ambient-temperature process is found to be more effective than conventional plasma treatments and reduced PEEK water contact angle from 78° to 37°." Further work on PEEK has been completed and published in J Roy Soc Interface. Negotiations are continuing between UCL-business, China and co-I Dr Huang on exploiting this concept via granted patents.
First Year Of Impact 2015
Sector Chemicals,Creative Economy,Education,Energy,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Cultural,Economic

Description The Royal Society International Exchanges
Amount £9,980 (GBP)
Funding ID 2013/R2 (inc CNRS) - Edirisinghe/Herath 
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2013 
End 11/2015
Description UCL/EPSRC Impact Acceleration Award
Amount £27,198 (GBP)
Funding ID PROJECT CODE : 537351 AWARD CODE : 159086 
Organisation University College London 
Sector Academic/University
Country United Kingdom
Start 09/2016 
End 02/2017
Description Evaluation of a Sri Lankan nano-hydroxyapatites for Orthopaedic Patterning 
Organisation University of Peradeniya
Country Sri Lanka 
Sector Academic/University 
PI Contribution Sri Lankan raw materials were used to synthesise hydroxyapatite and these were used in template-assisted electrohydrodynamic atomisation (TAEA) patterning and compared with commercially available hydroxyapatites
Collaborator Contribution Supply of Sri Lankan hydroxyapatite powder
Impact Preparation of Bone-implants by Coating Hydroxyapatite Nanoparticles on Self-formed Titanium Dioxide Thin-layers on Titanium Metal Surfaces W.P.S.L.Wijesinghe, M.M.M.G.P.G.Mantilaka, K.G.Chathuranga Senarathna, H.M.T.U.Herath, T.N.Premachandra, C.S.K.Ranasinghe, R.P.V.J.Rajapakse, R.M.G.Rajapakse, M.Edirisinghe, S.Mahalingam, I.M.C.C.D.Bandara, Sanjleena Singh, Mater. Sci. Eng. C, 63(2016)172-184. Facile Synthesis of Both Needle-like and Spherical Hydroxyapatite Nanoparticles: Effect of Synthetic Temperature and Calcination on Morphology, Crystallite Size and Crystallinity W.P.S.L. Wijesinghe, M.M.M.G.P.G. Mantilaka, E.V.A. Premalal, H.M.T.U. Herath, S. Mahalingam, M. Edirisinghe, R.P.V.J. Rajapakse, R.M.G. Rajapakse, Mater. Sci. Eng. C, 42(2014)83-90.
Start Year 2014
Description Orthopaedic materials patterning 
Organisation Orthopaedic Research UK
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Creating novel patterning routes for bioactive materials with orthopaedics as a focus
Collaborator Contribution Award of PhD and postdoctoral studentships
Impact The collaboration has resulted in the first patent of Orthopaedic Research (UK), formerly called The Furlong Trust. Multidisciplinary: Physical Science, Engineering, Life Science and Medicine. Dr Anouska Nithyanandan (post doc on EP/L024225/1) has regularly spoken/presented posters at their meetings.
Start Year 2008
Description Template-assisted patterning 
Organisation JRI Orthapaedics
Country United Kingdom 
Sector Private 
PI Contribution Participating in regular quarterly meetings with JRI staff
Collaborator Contribution 50% contribution to a UCL Impact studentship. Attending regular quarterly meetings in UCL.
Impact They have become partners of the EPSRC project EP/L024225/1. Collaboration has grown in that they were a central feature of an UCL/EPSRC IMPACT ACCELERATION AWARD which will run from October 2016 to February 2017.
Start Year 2009
Description An article comprising: a substrate; and over at least part of a surface of said substrate an outer coating of hydroxyapatite and an intermediate bonding layer bonded to said substrate and to said outer coating, wherein a mechanical interlock is present between said substrate and said outer coating. 
IP Reference EP2361100 
Protection Patent granted
Year Protection Granted 2011
Licensed Commercial In Confidence
Impact The Royal Society Brian Mercer (Innovation) Feasibility Award 2013. Also note that the patent is now granted in the USA and China. Patent No File Date Issue Date Country US9044528 30/11/2009 02/06/2015 United States CN102245220 30/11/2009 11/06/2014 China UK Priority Application: GB0821927.1 (Dec. 2008)
Description Key USA conferences such as TMS, MS&T and MRS -keynote/invited, annual invited participation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Sessions dedicated to novel manufacturing routes for biomedical engineering
Year(s) Of Engagement Activity 2018,2019,2020