“Fatigue testing of bone adhesives”

July 8, 2019

James M Flaherty Visiting Professorship 2018/19 Visit Report

Name:                               Dr Mark Towler

Dates of visit:                March-June 2019
Home institution:       Ryerson University / St Michaels Hospital, Toronto, ON.
Institution visited:     Dublin City University (DCU), primarily.

Further details: Although DCU was the host institution, I have also been undertaking laboratory work with Trinity College (TCD) and have met with senior faculty at the University of Limerick (UL), University College Dublin (UCD), NUI Galway (NUIG), the Tyndall Institute (TI) and Maynooth University (MU).  Further details are collated in the ‘Purpose of visit’ section.

Purpose of  Visit:    Collaborative research
Further details:

The research intention (in line with the Flaherty application) was to test chemotherapeutic cements that I had invented to determine their potential as bone void fillers in sufferers of osteosarcoma. This work would have been performed with DCU faculty (Drs’ Owen Clarkin and Nicholas Dunne), their clinical collaborators and two of my graduate students (Sunjeev Phull and Cina Mehrvar) that I would bring over to Ryerson using my own research funds. Unfortunately, the ethics process in DCU made it very difficult for non-DCU faculty to undertake cadaveric research on site and so the work programme was amended.  Instead of cadaveric work, I and five of my graduate students from Ryerson undertook a suite of characterisation tests on materials produced as a result of my existing, federally funded research program in Canada using equipment not available in Ryerson or St Michael’s Hospital but available in DCU and TCD.  I also made research trips to meet faculty in UCD, UL, UM, TI and NUIG and gave three presentations; the Flaherty talk at DCU (May 2nd) alongside two additional talks at UL (The Bernal Institute on June 6th) and TCD (The Amber Centre on June 14th) before returning to Toronto.

Field of study:     Biomaterials.
Visit details:
Research: The Nanobioanalytical Research Facility (NRF) is located on the DCU Campus and houses a large range of high-end research equipment that will allow it to create core capabilities across areas such as: Nanosynthesis, Nanometrology, Micro and Nano fabrication, NanoBioPhotonics and Analytical Characterisation. In order to further the research of my graduate students and to build publishable, collaborative research between Ryerson and DCU, five of my grad students (Cina Mehrvar, Sunjeev Phull, Amatulraheem Abadullah, Daniella Marx and Deanna Polintan; spent almost two weeks in DCU and TCD running characterisation tests on materials developed during their PhD studies using the facilitates in the NRF alongside additional facilities in DCU (Dr Clarkin’s laboratory) and TCD (Dr Aran Rafferty’s laboratory).

A brief list of research performed, and the student responsible, is included below:

Deanna Polintan: Differential Thermal Analysis (DTA) of proprietary bioglasses was performed. The analysis determined thermal properties of the glasses (glass transition, crystallization, melting point, exothermic and endothermic phenomena). The information elucidates the stability and likely reactivity of the glasses. It will facilitate determination of which glass composition will be most suitable for bone cement formation. Currently, an optimal composition of the Tantalum-containing 45S5 glasses is being developed for various bone cement applications. Testing performed @ DCU.

Cina Mehrvar: My research focuses on the development and commercialization of novel glass-based putties to augment sternal fixation. The chemistry of the material is patented. However, differences in the particle size of the glass component, the ratio of glass to liquid, the molecular weight of the acid component, as well as the presence of additives will all have profound effects on the viability of the adhesive in-vivo. In order to identify the glasses most suitable for putty formation, the following tests were performed:
• PSA (Particle Size Analysis): Previous versions of the adhesive used a glass particle size of <45μm. Upon implantation of these material into sheep, an inflammatory reaction with bone was observed. To address this, the particle size of the glass component was increased to 45-63μm; greater than the average size of a macrophage, thus reducing the risk of an inflammatory response. PSA confirmed that the particle size of the glass component was in the range of the target size. Testing performed @ TCD.
• XRF (X-Ray Fluorescence): This is capable of providing the elemental composition of a material and was used here to verify that the glass compositions fired were of correct composition. Testing performed @ DCU.

Sunjeev Phull:  My project focuses around the synthesis of a chemotherapeutic glass-polyalkenoate cement (GPC) for the reconstruction of bones damaged by cancer. These preliminary materials were characterised by a suite of tests.
• Differential Thermal Analysis (DTA) was performed to obtain the glass-transition temperature of the materials (Tg). This allows the determination of an appropriate temperature to anneal the glasses; a technique proven to increase the working time of the GPC resulting in clinicians having fewer time constraints in order to correctly place the cement while performing bone reconstruction surgery. Testing performed @ DCU.
• X-ray Fluorescence (XRF) was performed to determine the elements present within the bio-active glass network. Testing performed @ DCU.
• Surface area and porosity analysis: In order to determine the reactivity of these glasses, a technique called mercury porosimetry was used. Testing performed @ DCU.

Amatulraheem Abdullah: I helped my fellow students perform some of the tests required to analyze their glasses. Testing performed @ DCU and TCD.

Daniella Marx:  My research focuses on the osteoconductive properties of novel bone cements, more specifically the effects of strontium and zinc release from these cements on osteoblast differentiation, growth and mineralization. The following tests were used to determine the effect of glass particle size on the inflammatory response produced by macrophages and fibroblasts.
• X-ray Fluorescence (XRF): this determined the elemental composition of our cements, given the percentage of each element in the material. Testing performed @ DCU.
• Particle Size Analysis (PSA): This identified the particle size of the glass component of our cements. Testing performed @ TCD.
• Differential Thermal Analysis (DTA): This was employed to determine the thermal properties of the material. Testing performed @ DCU.

All five Ryerson graduate students enjoyed the experience (all of their costs were paid through my Canadian-based research funds; no costs were incurred by the ICUF), obtained valuable data for their PhD theses and have developed plans to use other equipment in TCD and DCU should a more formal working agreement between Ryerson and the Irish institutions be developed.

Working in Prof O Clarkin’s laboratory, DCU

Working in Dr A Rafferty’s laboratory, TCD.


Building links:

Dr Towler met with:
Prof Catriona Lally (Professor in Bioengineering) @ TCD to discuss European Research grants and to arrange a date for Towler to give a seminar @ TCD. Following the seminar on June 14th, Towler also met with Profs. Fergal O’Brien and Danny Kelly (both AMBER), to discuss future collaboration.
Prof Kenneth Stanton (Head, Mechanical and Materials Engineering) @ UCD to discuss research options in Dublin.
Profs Edmond Magner (Dean, Faculty of Science & Engineering), Noel O’Dowd (Professor of Mechanical Engineering) and Stuart Hampshire (Emeritus Professor) @ UL for a tour of the new Bernal Institute. Towler returned to UL to give a seminar to the Bernal Institute on June 6th.
Prof. Alan Ryder (Professor of Chemistry) @ NUI Galway to discuss funding options for a collaborative project using Towler’s patented technique and clinical links and Ryder’s spectroscopy equipment and industrial links to develop a laser-based diagnostic for inflammatory arthritis.
Prof Bernard Mahon (Professor of Biosciences, ex-VP research) @ NUI Maynooth to discuss biochemistry research and cell culture services in NUIM.

These trips were designed to either re-engage collaborative research (I have published with Stanton, Hampshire and Mahon before) or stimulate new research streams (I am working on a novel diagnostic to diagnose arthritis with Prof Ryder and hope to drive some new clinical ideas with Prof Lally).

Travelling to meet with Dr A Ryder, NUIG (L-R: Polintan, Phull, Dr Clarkin, Mehrvar, Marx)

Presentations: I gave the Flaherty Lecture ‘A Novel Screening Tool for Fracture Risk’ on the 2nd May as part of the DCU Annual Research day which was well received.

Although the Flaherty visiting position ended its three month tenure on 2nd June I remained in Ireland until 16th June. In that two-week window I gave research seminars at the AMBER institute in Trinity College (June 14th) and the Bernal Institute in University of Limerick (June 6th). Due to time constraints and faculty availability these seminars could not be conducted in the three-month Flaherty window but the invitations to give these talks did spin off from visits to these institutions facilitated by the ICUF funds.


James M Flaherty Visiting Professor talk, DCU, 11th May 2019

Future collaboration:

DCU have extended my tenure for 18 months until the end of 2020, meaning that I will have office space and access to labs whilst I am on an extended sabbatical from Ryerson. The collaborative data already produced and that forthcoming will result in three joint TCD/Ryerson and UCD/ Ryerson manuscripts for publication in the scientific literature and these manuscripts will acknowledge the funding support of the ICUF. At least one of my current tranche of grad students will apply for graduate scholarships through the pertinent ICUF program in order to continue the collaborative research between Ryerson and the Irish institutions. As the recipient of over C$1M Canadian federal funding in the last year alone it is likely that I will travel to Ireland several times over the next year to cement existing research relationships with DCU and TCD and build on the preliminary relationship with Dr Ryder (NUI Galway) to develop a spectroscopic diagnostic for inflammatory arthritis; a research space that I have two publications and a patent application in and one that Dr Ryder has a wealth of experience and spectroscopic experience that will help in the development of a Canada/Ireland developed novel clinical diagnostic.

1. Office space and lab access given by DCU for the next 18 months.
2. Laboratory research performed with TCD and DCU expected to lead to three peer-reviewed publications
3. Presentations given at DCU (Flaherty talk), TCD and UL.
4. Meetings with senior faculty at TCD, DCU, UL, UCD, TI, NUIG and NUIM to determine means of continuing Canadian/Irish research collaboration.