Joint & Bone Initiative

Funding Decisions

The BJI Catalyst Grants competition is pleased to announce this year's awardees.  There were many meritorious applications; however, we were only able to fund a portion of all of the excellent research proposed.

Congratulations to this year's awardees.

2020 Awards - Fall Competition

Review Committee - Ryan Willing (Chair), Jennifer Boyle, Parham Rasoulinejad, Mamadou Diop

Funding Period: April 1, 2021 to March 31, 2023

Introductory Showcase Deadline: Oct 2021; Mid- term Showcase Deadline: May 2022; Final Showcase Deadline: Mar 2023

Applicants Home Faculty Title

Appleton, Tom*

Birmingham, Trevor

Walton, David

MacDermid, Joy

Schulich

Health Sciences

Health Sciences

Health Sciences

 

Biological mechanisms of biomechanically-induced pain in knee OA
Pain during some types of physical activity is the cardinal symptom of knee osteoarthritis (OA). Although the biological mechanisms activated by painful physical activity are likely to be critical treatment targets, very little is known. This new collaboration will integrate gait biomechanics and biology of inflammation research to discover why OA makes our knees hurt when we “walk this way”.

Battié, Michele*

Drangova, Maria

Holdsworth, David

Junmin, Liu

Hwang, Jiawei

Laura Gibbons

Health Sciences

Schulich

Schulich

Schulich

External Partner

External Partner

Quantatative MRI protocols for Assessing Intervertebral Disc Degeneration - Back pain and related disability are a major burden on affected individuals, their families and societies, worldwide. Intervertebral disc degeneration is suspected as an underlying culprit. Yet widely available measures of disc degeneration are grossly inadequate, hampering related research. Our group aims to develop, assess, and standardize advanced quantitative MRI sequences to fill this need.

Walton, David*

Dickey, James

MacDermid, Joy

Marignani, Marilena

Klubowica, Dorota

Nilam, Zikra

Health Sciences

Health Sciences

Health Sciences

Clinician Partner

Trainee

Trainee

Psychometric analysis of a new Western Breast Interference Scale - Breast reduction surgery has been indicated for women with macromastia and comorbid spinal pain for several years, though the evidence base to support its effectiveness is notably sparse. We have created a new patient reported outcome scale for breast-related interference to be used in research in women with spinal pain. Reliability, validity, and usability will be evaluated in this project.

2019 Awards - Fall Competition

Review Committee - Jim Dickey (Chair), Jennifer Boyle, Lisa Cechetto, Jayne Garland, Alan Getgood, Lisa Hoffman, Cathie Hofstetter, Marlys Koschinsky, Jim Lacefield, Joy MacDermid, Edward Vasarhelyi, Ryan Willing

Funding Period: April 1, 2020 to June 30, 2022

Introductory Showcase Deadline: Oct 2020; Mid- term Showcase Deadline: June 2021; Final Showcase Deadline: June 2022

Applicants Home Faculty Title

Stock, Jay*

Holdsworth, David

Nelson, Andrew

Social Science

Schulich

Social Science

 

Design and validation of a portable cone-beam μCT scanner
A significant decrease in bone quality occurred over the past 10,000 years, in response to major shifts in human diet and activity. We will design a new High-resolution portable CT scanner to investigate the internal bone quality of humans worldwide, at different times in the past, to understand why human have low bone mass.

O'Gorman, David*

Holdsworth, David

Athwal, George

Faber, Kenneth

Schulich

Schulich

Schulich

Schulich

Detecting periprosthetic joint infection in mimetics by mass spectrometry - While infections of artificial    'prosthetic' joints are rare, they are devastating for the patients who suffer them. We will use our human cell-based laboratory models of artificial joint infections to determine if a technique called mass spectrometry can distinguish “uninfected” from “infected” joint tissues. If successful, it may be possible to translate this technology to the operating room.

Lalone, Emily*

Langohr, Daniel

Suh, Nina

King, Graham

Engineering

Engineering

Schulich

Schulich

Development of a Total Wrist Arthroplasty System to Improve Patient Outcome - End stage wrist arthritis is often treated surgically using wrist ‘fusion’ improve pain.   This, however, significantly reduces range of motion and therefore wrist function.   Alternatively, total wrist arthroplasty which replaces the wrist joint with an articulating implant; however, current designs cause numerous problems. The objective of our proposed work is to develop a load sensing wrist implant.

Hunter, Susan*

Payne, Michael

Viana, Ricardo

Bartha, Robert

Health Sciences

Schulich

Shulich

Shulich

Imagined and real walking effects in people with lower extremity amputation
 - Every year in Canada about 7,500 people lose a limb, the leg is the most common.   Learning to walk with a prosthesis requires intensive rehabilitation. Imagined walking activates the same brain areas as real walking. We will use brain imaging technology to evaluate brain activity during real and imagined walking in people with leg amputation. This study will lead to the development of a rehabilitation program to improve walking and quality of life for people with a leg amputation.

2019 Awards - Spring Competition

Review Committee - Jim Dickey (Chair), Tom Appleton, Jennifer Boyle, Lisa Cechetto, John Coderre, Lisa Hoffman, David Holdsworth, George Knopf, Jim Lacefield, Brent Lanting, Joy MacDermid

Funding Period: September 1, 2019 to November 30, 2021

Mid- term Showcase Deadline: February 2021; Final Showcase Deadline: November 2021

Applicants Home Faculty Title

Birmingham, Trevor*

Dianne Bryant

Bert Chesworth

Joy MacDermid

Brent Lanting

Jackie Marsh

Matthew Teeter

Health Sciences

Health Sciences

Health Sciences

Health Sciences

Schulich

Health Sciences

 Schulich

Rethinking Rehabilitation After Total Knee Arthroplasty: A Pilot RCTCurrent rehab after knee replacement surgery does not adequately improve patient symptoms or activity level. This pilot study will test the feasibility and preliminary outcomes of a new rehab strategy. Traditional patient-reported and performance-based measures will be combined with wearable devices and machine learning. Data will support grant applications for a definitive multi-centre cluster randomized trial comparing clinical and cost-effectiveness.

Degen, Ryan*

Jackie Marsh

Blayne Welk

Schulich

Health Sciences

Schulich

Current trends in hip arthroscopy utilization and long-term cost-efficacy - This study will evaluate current trends in hip arthroscopy utilization, focusing on 40- to 60-year-old patients. There is evidence to suggest higher failure rates and conversion to total hip replacement in this population. Therefore, we aim to report on procedural trends, post-operative resource use and re-operation rates. This data will be used to establish a model to predict long-term cost efficacy.

Gillies, Elizabeth*

Tom Appleton

Frank Beier

Science

Schulich

Schulich

Intra-articular Delivery of PPARdelta Inhibitors for the Treatment of OA - Osteoarthritis (OA) is a progressive disease involving the breakdown of joint tissues. Despite its high prevalence, there are currently no medications that slow or halt the progression of OA. This project will evaluate a new potential disease-modifying drug for OA. The drug will be delivered to joints by an injection and then released over a period of 3 months using a new delivery vehicle.

Seguin, Cheryle*

David Holdsworth

Andrew Leung

Schulich

Schulich

Shulich

Investigating the effect of anabolic steroids on the intervertebral disc - The proposed research describes a mechanistic study to follow up on clinical observations of increased intervertebral disc height in suspected users of anabolic steroids. This perhaps unintended biological effect may serve as a potential disease-modified treatment for disc degeneration and associated back pain.

Shoemaker, Kevin*

Tom Appleton

Emily Lalone

Ting-Yim Lee 

 Health Sciences

Schulich

Engineering

Schulich 

Bone Blood Flow in Humans: Impact of venous occlusion and hand osteoarthritis - Accumulating data support a role for vascular pathology in joint disease with emphases on venous congestion and/or vascular disease. However, very little is known about bone blood flow (BBF) in humans. We will adapt dynamic contrast-enhanced computed tomography to quantify BBF in healthy individuals or those with vascular disease at baseline and following venous occlusion.

Willing, Ryan*

Frank Beier

Trevor Birmingham

Tim Burkhart

David Holdsworth

Engineering

Schulich

Health Sciences

Engineering

Schulich

Computational modelling to elucidate the aetiology of knee osteoarthritis - Knee osteoarthritis (OA) is a leading cause of pain and disability. Aberrant mechanical loading through the joint is believed to be a primary aetiological factor. Unfortunately, there is currently no way to directly measure these loads. The overarching goal of this research is to develop computational mechanical models of knee loading to compare with quantitative measures of OA progression.

2017 Awards

Applicants Home Faculty Title

 Appleton, Tom

Beier, Frank

Lanting,  Brent

Mrkobrada, Marko

Schulich

Schulich

Schulich

Schulich

The association of synovitis with patient outcomes after total knee arthroplasty for end-stage osteoarthritis

Summary: Most people think of knee osteoarthritis (OA) as a non-inflammatory “wear-and-tear” disease of the joint, but inflammation is an important feature of knee OA. Thickening of the joint lining (synovitis) causes fluid to accumulate in the joint and is associated with increased pain and stiffness. At end-stage disease, people often require joint replacement surgery. While most people experience good outcomes from the surgery, a significant proportion have persistent pain, stiffness, and swelling. This team, led by an early career clinician-scientist, set out to 1) explore the association among synovitis, symptoms (pain and stiffness) and joint function (ability to walk, strength testing) and 2) determine if particular inflammatory features such as macrophage infiltration and polarization are associated with changes in patient knee arthroplasty outcomes. Impact: The proposed work generated interest in multiple groups and attracted new funding. The Scientific Director granted an extension to June 2020 to expand the scope of the work and potential impact. Ninety patients were recruited using a purposive sampling approach (balancing OA criteria – post-traumatic or metabolic – and sex ratio). Synovitis was assessed pre-surgery and 3-months post using non-invasive imaging along with other variables. Follow-up at 12-months post is ongoing. Cell-type specific RNA sequencing profiles were analyzed to examine the difference between OA conditions and results will be presented at OARSI 2020. Pain phenotypes associated with inflammation were identified and will be presented at IWOAI 2020. A new relationship of inflammation with impairments in knee function was discovered. An ACR abstract was submitted and subsequently nominated for CHRSF oral abstract. Six manuscripts are under development. This work catalysed new project ideas, collaborations and opportunities for leveraged funding: Association of gait biomechanics with inflammation (with Birmingham and 4 co-supervised grad trainees supported by CMHR, CIHR, or CGS-M); New 3D ultrasound project to assess inflammation in OA patients (with Fenster supported by a Schulich CRSG award of $33K); Relationship of inflammation to post-op outcomes (application in progress with Lanting, MacDonald, Vasarhelyi); and Integrated omics project (transcriptomics + mechanomics) looking at mechanobiology of inflammation related to specific surface contact mechanics (NFRF-Exploration application in progress with Lalone).

Holdsworth, David

Lalone, Emily*

MacDermid, Joy

Suh, Nina

Schulich

Engineering

Health Sciences

Schulich

Effect of Distal Radius Fractures on Joint Mechanics, Osteoarthritis and Patient Outcomes

Summary: A substantial proportion of post-traumatic osteoarthritis is preventable; unfortunately, the rates of arthritis following orthopaedic injury of the wrist are unacceptably high. Patients experience pain when they ‘load’ or use their hands and wrist, yet we rarely examine patients’ function and mechanics. Obtaining functional range of motion and weight bearing scans would provide surgeons with unique information about joint loading and joint contact mechanics that may help determine optimal surgical fixation needed (based on timing and degree of malunion) to prevent persistent symptoms of post-traumatic osteoarthritis. Led by an early career researcher, this team set out to validate the use of extremity/peripheral CT scanner to generate image and functional data (i.e. load-bearing contact mechanics) that would enable examination of changes in joint alignment and their contribution to the development of arthritis. Impact: The team secured additional funds to support this work (Canadian MSK Rehab Research Network Pilot Grant 10K; Lawson Health Research IRF 15K; Discovery Grant 147K). They collected pilot data that is now being incorporated into a CIHR Project Grant Proposal for 350K. Images were obtained from over 60 individuals (healthy and post-fracture) to develop scanning protocols (3D and 4D) for positioning and loading of the wrist during scanning. Currently this work has led to the preparation and submission of three papers that have been accepted with revisions and 4 more in preparation (journal of hand surgery, journal of orthopedic research and journal of biomechanical engineering). The work was expanded to also examine inflammation following fracture as a result of new collaboration with Aaron Fenster (expert in 3DUS) and Tom Appleton (rheumatologist)(WSS-CIHR Success Seed 21K). This work also extended to a parallel project at the knee which was recently funded (New Frontiers in Research Fund – Exploration 250K).  Also new to the team, Nik Knowles is working on quantitative measures from CT (BMD) as part of his post-doc with Steve Boyd at McCaig Institute in Calgary. The team continues their work with a larger data collection protocol that includes additional imaging and types of injury (e.g. scaphoid fracture and midcarpal instability). Via a new partnership with Intergra Freedom, the team will explore wrist arthroplasty and the use of 4DCT scans. Future studies awaiting ethics approval will build on the results of this study to examine the shoulder joint with George Athwal and a new trainee.  The team has already done 3 poster session presentations at ORS and IMNO.

Rasoulinejad, Parham*

Teeter, Matt

Schulich

Schulich

Static and Fatigue Testing of a Novel Fusion Construct for Atlantoaxial Instability

Summary: Fusion of C1 vertebrae to C2 vertebrae is a common procedure used in cases of trauma, tumor, inflammatory disease and congenital conditions of the spine. Current techniques have been used for over two decades and often require implantation of four screws and two rods to achieve stability (Harm's procedure). These procedures involve long operative times, substantial blood loss, and prolonged recovery periods. They are also technically challenging technology for the operative team. This project team set out to design and develop a novel clamp, specific to the C1 vertebra, that eliminates the need for placement of lateral mass screws into C1; thereby, making the procedure less challenging and decreasing operative time and blood loss. Impact: The team partnered with ADEISS, an additive manufacturing company in London, ON, to advance the development of the implant from a benchtop prototype to clinical grade (test ready). The 3D printed assemblies led to major research advancements and submission of a full US patent and PCT. Medical grade contract manufactures were secured (3DS - Contract manufacturer for additive implant; Coorstek - Contract manufacturer for machining; ADEISS - R&D to advance implant to clinical stage; JTL - 3rd party testing lab for ASTM 1717) and product qualification runs were completed. Catalyst Grant support demonstrated that this is a promising area of work and future developments will continue as the team conducts mechanical testing and pursues an investigational trial with Health Canada. Cash and in-kind prizes were leveraged to support current and future work (Techalliance BURST 70K; Waterloo Velocity Fund 40K). Once meetings with the FDA to de-risk the regulatory road map are concluded, the team plans to pursue private financing or licensing deals. Conference presentations were delivered at the 2019 Orthopaedic Research Society and Canadian Spine Society annual meetings to discuss the design and commercialization process of the implant as well as the study on C1 morphology used for implant sizing. Publications on the same topics were submitted (results pending). The design and biomechanical testing of the fusion device has been published.

* nominated applicant/main contact person

2016 Awards

Applicants Home Faculty Title

Athwal, George 

Doherty, Chris 

Faber, Ken

Grewal, Ruby  

King, Graham

MacDermid, Joy*

Schulich

Schulich

Schulich

Schulich

Schulich

Health Sciences

Long-term healthcare consequences of upper extremity fractures: A population perspective

Summary: Much time, effort and finances have gone into the collection of population health data because it can provide important insights that other types of research cannot. This project aimed to use population data about people who have hand or arm trauma to understand the fracture patterns, the use of opioids and the risk of future broken bones in the arm, hip and spine fractures (indicative of osteoporosis). The goal was to describe the patterns of fractures and use data to understand the pathways of risk decades later by using data on Ontarians managed by The Institute of Clinical Evaluative Sciences (ICES). The team focused on identifying issues (e.g. social factors, geographic regions, co-morbid health problems) that should be considered as key to reducing future disability and death. Impact: The lead applicant completed the 2-year ICES Scholar training program and is continuing on a pathway to become a ICES scientist. A paper describing the fracture patterns and social determinants of health for more than 200,000 people having a 1st upper extremity fracture in Ontario over 4 years was submitted for publication. A 2nd paper describing the rate of opioid prescription filling following a 1st upper extremity fracture is being finalized. Papers in progress will address predictors of persistent opioid use, and future fracture. Catalyst funds were leveraged to secure ICES expert time via the ICES Scholar program. The ICES work was incorporated into a CIHR team bone grant on distal radius fractures (ending 2020) and a successful submission for a CIHR Foundation grant (2019-2026- $1.8M) that will fund an ongoing line of research on population level musculoskeletal health services.

Beier, Frank

Diop, Mamadou*

Schulich

Engineering

Can joint blood flow be used to monitor treatment response in rheumatoid arthritis? 

Summary: Rheumatoid arthritis (RA) is a chronic disease with no cure that is associated with pain, reduced quality-of-life, and loss of productivity. New drugs have revolutionized its treatment; however, they are expensive, have adverse effects, and do not work in 30% of RA sufferers. The lack of adequate monitoring tools to detect positive physiological changes means that some patient receive treatment for up to one year with no benefit. This team hypothesized that physiological changes could be detected using their optical technique and serve as an early indicator of treatment response. Using a well-established rodent model of RA and comparator groups (group A - anti-inflammatory drug: etanercept; group B – analgesic: tramadol hydrochloride) the goal was to test the optical technique and validate results against functional computed tomography and histology. Impact: The team demonstrated that joint blood flow could be used to monitor disease activity in a rat model using both the optical technique and CT perfusion. During the project the optical technique was enhanced in terms of sensitivity. Varied disease severity in the animal model effected study progress. The team plans to repeat the study with a larger sample size to demonstrate that joint blood flow can be used to monitor treatment response. They also plan to conduct studies that focus on perfusion in the hands and the clinical compatibility of the technique. All three students working on the project received financial support including NSERC-Canada Graduate Scholarship, NSERC-USRA, and CMHR, BJI. Catalyst funds were leveraged to conduct additional research with CT perfusion on the same animals supported by new collaborations with David Holdsworth. Two conference presentations were submitted and 4 conference presentations were delivered at various North American sites. A paper describing the quantification of joint blood flow by dynamic contrast-enhanced near-infrared spectroscopy was published (Jan 2020).

Burkhart, Timothy*

Getgood, Alan

Engineering

Schulich

Optimizing surgical interventions to mitigate the effects of post traumatic osteoarthritis

Summary: Approximately 14% of anterior cruciate ligament (ACL) reconstructions fail, with the development of osteoarthritis (OA) occurring in upwards of 60% of patients.  Among the causes of sub-optimal ACL reconstruction outcomes, the inability to return the kinematic profile of the joint to pre-injury patterns is one of the most common. The overall objectives of this research was to: 1) determine the contribution of ALL reconstructions to anterolateral knee kinematics; 2) optimize the characteristics of extra-articular reconstructions; and 3) develop and validate computational models of knee instability and reconstruction. Impact: Using a CT compatible knee joint simulator, cadaveric knees were tested in response to two different extra-articular reconstructions (ALL and lateral extra-articular tenosdesis). The team quantified regional strain distributions in the ACL and the length changes in relevant tissues on the lateral aspect of the knee. They also created and validated a finite element model to measure bone strains in the tibia and used this model to develop a method to reduce the incidence of bone fracture (currently exploring tech transfer options). Lastly, they assessed the lateral compartment pressures in the knee when the surgeon performs an LET with and without a meniscus. The project led to new collaborations with David Holdsworth who assisted with the imaging aspects of the work and Ryan Degen who assisted with the surgical procedures. The catalyst funds allowed the team to explore research techniques that are more efficient and provide greater amounts of data. These techniques can be used to explore an infinite number of conditions from a single set of specimen specific data. The tissue strain measurement techniques enable the objective measurement of tissue behaviour in a way that was not possible before. Smith and Nephew has committed 3 years of funding to expand this work and an NSERC Discovery of 250K was secured. A CIHR_CHRP was submitted (results pending). One publication is in press, one is under review, four were submitted, and two more are planned. Three conference presentations were delivered and four more were submitted.

Dickey, Jim

Walton, David*

Health Sciences

Health Sciences

Development and implementation of a VR-based simulator to evaluate the relative role of mechanics and startle in clinical neck pain mechanisms

Summary: Persistent pain and disability following otherwise ‘minor’ musculoskeletal injuries such as whiplash, is poorly understood.  About 50% of people following a motor vehicle collision will report persistent problems 12 months later, while the rest recovery uneventfully. In most cases, the parameters of the event (vehicle speed and direction) and diagnostic imaging cannot explain the symptoms. Research in this area is challenging because participants can only be recruited following the event and so the immediate event parameters such as stress, startle, pain processing, and biomechanics cannot be explored. This team aimed to complete the development of a virtual reality-based fully immersive road traffic collision simulator to enable advanced exploration of such parameters. Secondary objectives included: 1) the analysis of feasibility, safety profile, and estimated normal responses in key outcomes, and 2) estimation of the magnitude of association between key physiological and psychological markers of startle/distress/pain modulation. Impact: This project led to a new collaboration with computer programmers Karsten and Mathias Babin who designed the only immersive virtual reality car-crash simulators in Canada. Extensive testing with both dummies and live participants was completed and the system is now ready for use as a research tool. Thirteen different pre-programmed paths are available to avoid predictability. The perturbations do not cause tissue damage in the neck or other tissues, but offer a realistic experience of startle and loss of control so that physiologicial metrics of stress/startle can be collected. Future studies will explore the relationship between the metrics of startle and pain sensitivity/modulation before and after exposure to the simulator. A Lawson Health Research Institute Earl Russell Trainee Grant of 25K was secured to continue this work. Further development is required prior to seeking additional external funding. Local presentations have been delivered and conference presentations have been submitted.

Flynn, Lauren*

Seguin, Cheryle

Engineering, Schulich

Schulich

Development of tissue-specific instructive matrices for intervertebral disc regeneration

Summary: Chronic back pain associated with degenerative disc disease is a debilitating condition that negatively impacts the quality of life of many Canadians. Pain management and surgical intervention are the current treatment options that have limited efficacy and can lead to numerous complications. Cell-based therapies involving the delivery of pro-regenerative stem cells into the intervertebral disc (IVD) hold promise as a new treatment approach. This research project brings together a new research team to develop novel cell-instructive biomaterials for stem cell delivery to promote IVD regeneration. The approach will involve encapsulating cells within a naturally-derived polymer composite that forms a gel at body temperature, studying their proliferation and differentiation, and tuning the platform to enhance cell viability and lineage-specific differentiation. Impact: The team optimized and shortened the protocol used to generate the decellularized nucleus pulposus (DNP) while balancing the retention of key extracellular matrix (ECM) constituents with effective extraction of cellular components. Biochemical characterization of the DNP was performed, including comparison to the ECM composition in native tissues. New collaborations with Brian Amsden supported the development of the hydrogel delivery vehicle. Ongoing research is focused on investigating the response of cell populations encapsulated within the methacrylated chondroitin sulphate (MCS) hydrogels incorporating the DNP. Catalyst funds were leveraged to secure a collaborative New Ideas Grant from the Ontario Institute of Regenerative Medicine in 2019 ($75,000). NSERC RTI (Biomech Testing Suite) of 150K and scholarship funding of $48k via the CONNECT! NSERC Training Program were also secured. A poster presentation was delivered at the Canadian Bone and Joint Conference in 2018. Further, an oral presentation was given at the Canadian Biomaterials Society Annual Meeting in 2019, which received both a competitive travel award and the top oral presentation award for a Master’s student.

Marsh, Jackie*

Petrella, Robert

Health Sciences

Schulich

Cost of implementation and patient resource use associated with a community-based targeted education and exercise program to limit the burden of hip and knee osteoarthritis (OA)

Summary: Osteoarthritis (OA) is a leading cause of disability and reduced quality of life that contributes to substantial direct and indirect costs for patients and the healthcare system. The prevalence of hip and knee OA is increasing and although current evidence-based guidelines recommend education and exercise as the first line treatments, there is a lack of easily accessible exercise programs. Furthermore, these interventions are not covered by provincial health plans. The goal of this project was to evaluate the costs of implementing a targeted education and exercise program for people with hip and knee OA in a private physical therapy clinic. Impact: This team generated estimates of the direct and indirect costs of healthcare resource use by patients with hip and knee OA. They also produced a detailed description of the program implementation cost. Health related quality of life, pain, and healthcare resource use was compared at twelve months following program initiation. The catalyst funds led to the development of a future research plan to evaluate similar education and exercise programs in hip and knee OA patients following joint replacement surgery. This will inform evidence-based rehabilitation strategies to optimize patient outcomes, satisfaction and costs. Through this project new collaborations were established with Aileen Davis (physiotherapist and clinical epidemiologist) and Jackie Sadi (MSK Physical Therapist). Proposals were submitted to the Arthritis Society and CIHR to continue this work.

Price, Aaron*

Trejos, Ana Luisa 

Walton, Dave

Engineering

Engineering

Health Sciences

Wearable Smart Polymer Stretch Sensors for the Clinical Assessment of Patient Recovery From Neck Injury 

Summary: Motion at a specific joint is used to measure the degree of impairment in injured patients. Traditionally, an adjustable or wearable protractor known as a goniometer is used to directly measure range of motion during a carefully controlled clinical assessments by physiotherapists as opposed to during patients’ normal daily activity. For complex joints such as the neck with several axes of mobility and range of motion, conventional goniometers lack sufficient precision to provide meaningful measures. To mitigate these limitations, this team propose to develop a non-intrusive wearable device that can track daily motion of a patient’s neck by integrating soft sensors within a wearable tape. Impact:A proof-of-concept prototype of single-axis self-powered wearable joint mobility sensor was realized and a specialized mechatronic data acquisition module was developed to manage and condition the sensor output. These activities have directly led to significant support from an industrial collaborator, Mark MacKenzie (DAVWIRE) President & CEO, Defense & Aviation Wiring Inc., who have appropriated significant cash and in-kind support for follow-up research activities. Future developments are planned including a simulated clinical joint mobility assessment in conjunction with high-precision lab-based sensors. Catalyst funds were leveraged with a OCE VIP I program (w. DAVWIRE) 25K cash 15K in-kind and the NSERC Engage (w. DAVWIRE) 25K. CIHR CHRP (NSERC Partnered, w. DAVWIRE) 65K was submitted. ORF Round 9 600K was submitted but not funded. DAVWIRE also partnered on 2 two-year Mitacs Elevate applications to hire a postdoctoral fellow for continued to development of wearable energy harvesting devices ($120K – under review) and to hire a MESc student ($60K - submitted). Unfunded application will be repackaged to target other opportunities. Results were presented at a national conference and a publication on wearable capacitive sensor for neck mobility measurement is under development.

Rasoulinejad, Parham*

Teeter, Matt

Schulich

Schulich

Design & Development of a novel stand-alone lumbar fusion device

Summary: Lumbar fusion (immobilization of the intervertebral joints) is among the most commonly performed spinal surgeries to treat a number of pathologies including: spinal stenosis (narrowing), spinal deformity (unnatural curvature or defect), and radiculopathy (pain and neurological symptoms) secondary to degenerative conditions, trauma, and cancer. Current techniques have been used for over three decades and often require implantation of interbody cages, four screws and two rods to achieve stability. Procedures involve long operative times, substantial blood loss, and prolonged recovery periods. This project team set out to design and develop a novel standalone intervertebral device that eliminates the need for pedicle screws and rods; thereby, decreasing operative time, blood loss, incision size, and procedural costs. Impact: The team has developed multiple design iteration. The project has been challenging due to specialized tooling needed to insert the new implants in a way that is compatible with minimally invasive spinal surgery. To that end, the surgeons at LHSC collaborated with the department of engineering and utilized machining resources at Western as well as the rapid prototyping abilities of ADEISS to create a final design that is truly novel and functional.  The team is currently testing the newest and most novel design iteration in cadaveric specimens to confirm biomechanical stability in comparison to the current gold standard design and procedure. If successful, the team plans to work closely with industry partners to license the product and pursue approvals (an ITA via Health Canada and or the 510K pathway via FDA) to conduct a rigorous clinical trial of this new product.

* nominated applicant/main contact person

2015 Awards

Applicants Home Faculty Title

Campbell, Craig

Hoffman, Lisa*

Leask, Andrew

Schulich

Schulich

Schulich

The role of CCN1 in Duchennes Muscular Dystrophy

Summary: Duchenne Muscular Dystrophy (DMD) is a debilitating disorder with no cure that results in profound muscle weakness for 1 in 3300 boys. The CCN matricellular family of proteins regulates a variety of cell functions including wound repair and angiogenesis that is associated with the inflammatory response that leads to fibrosis in DMD patients. CCN1 is known to have a role in the inflammatory response, but it remains uncharacterized in DMD. We hypothesized that CCN1 is upregulated in response to increasing severity of fibroses. The team assessed this using two different staining protocols (DAB and immunofluorescence) and three different disease severity mouse models (1- the weakly affected mdx mouse that lacks dystrophin, 2- the mdx utrn+/- mouse lacking one utrophin allele with intermediate disease severity, and 3- the severely affected mdx utrn-/- mouse lacking two utrophin alleles) compared to wildtype controls. The study revealed that using DAB, CCN1 was found to be significantly upregulated in severely fibrotic mdx utrn-/- mice compared with less affected/non-fibrotic DMD genotypes and healthy wild-type controls. When using fluorescence, moderately fibrotic mdx utrn+/- mice were found to have upregulated CCN1 expression compared to wildtype controls and non-fibrotic DMD mice. As such, this study supports a role for CCN1 being present in the course of fibrosis progression in DMD. Impact: Further studies are underway to assess the potential of CCN1 as a biomarker of fibrosis in this neuromuscular disorder. If identified as an optimal biomarker of fibrosis in DMD patients, current partnership with Industry Partner, Akrivis Technologies LLC will be expanded to develop an anti-CCN1 targeted therapy. The catalyst funds enabled the team to engage 2 trainees and established one new academic collaboration. The team foresees submitting proposals to CIHR, NSERC and possibly Heart & Stroke within the next 1-2 years. The results have been presented at the Gordon Research Conference.

Ardelean, Daniela

Barra, Lillian*

Cairn, Ewa

Schulich

Schulich

Schulich

Autoantibodies in the Unaffected First Degree Relatives of patients with Rheumatoid Arthritis and Juvenile Inflammatory Arthritis

Summary: The purpose of this study was to investigate unaffected first-degree relatives (FDR) of rheumatoid arthritis (RA) and juvenile inflammatory arthritis (JIA) as a model for the pre-disease state of these autoimmune disorders. RA and JIA are diseases with unknown cause that lead to joint pain, damage and functional impairment. Specifically, the team was focused for this project on investigating the role of anti-citrullinated protein/peptide antigens (ACPA) and anti-homocitrullinated protein/peptide antibodies (AHCPA) in this population. They found that unaffected FDR of adult RA patients expressed IgG AHCPA more commonly than healthy controls, but that other isotypes were infrequently expressed.  Unlike ACPA, AHCPA were not associated with joint pain, smoking, or a known genetic risk factor for RA (Bell DA, et al. 2017). In preliminary experiments, sera from RA patients positive for both ACPA and AHCPA induced joint swelling when injected into mice after citrullinated proteins were injected into the joints of these mice.  Histologic examination of the joints revealed synovial thickening and inflammatory cell infiltration. Impact: Future Studies related to this work will include the prospective monitoring FDR who were AHCPA-positive, without any evidence or symptoms of arthritis, to determine whether they develop RA over time. Also, the team will continue to investigate whether AHCPA is arthritogenic using mouse models. A donation from St. Joseph’s Health Care (SJHC) Foundation will support the monitoring of unaffected FDR. Recruitment to this cohort is ongoing without funding pending approval by the SJHC Foundation. Once additional pilot data is available, the team intends to leverage support from other granting agencies for ongoing studies that involve their novel animal model for RA.   

Athwal, George

Ferreira, Louis*

Schulich

Engineering

Development and Validation of Patient-Specific 3D - Printed Bone Models with Heterogeneous Bone Density Distributions for Implant Design and Surgical Evaluation

Summary: Synthetic (3D-printed) bones that are representative of patients with various types of osteoarthritis are needed to address the shortage of cadaveric joints available to researchers. This team set out to develop synthetic shoulder joints that model the physical characteristics of natural bones of arthritic patients using computed tomography (CT) and modern 3D-printing methodologies. The goal was to develop an alternative to cadaveric joints that would improve our ability to evaluate current treatment options for painful joints, to advance our approach to developing patient-specific joint implants, and to expand surgical skills training opportunities. Ultimately, the vision was to enhance clinical outcomes following surgical procedures. Impact: The team was successful in developing a micro-CT compatible uni-axial joint loading device. They evaluated simulation software with a 100-fold decrease in computational requirements for micro-level simulation of bone. Through this project, new collaborations were formed with an academic investigator and trainee. The team continues their work with a focus on improving understanding of the mechanical properties and computational models of the shoulder for the purpose of enhancing implant designs and evaluation of surgical approaches. The funds were leveraged to secure funding from the St. Joseph’s Foundation funding to purchase a custom-designed CT-compatible robotic joint loading mechanism ($30,000). Results are available in two successfully published article (Knowles NK, Reeves JM, Ferreira LM. Quantitative Computed Tomography (QCT) derived Bone Mineral Density (BMD) in finite element studies: a review of the literature. Journal of Experimental Orthopaedics, 2016;3(1):36 and Reeves JM, Knowles NK, F, Athwal GS, Johnson JA. Methods for Post-Hoc Quantitative CT Bone Density: Phantom-only and Regression. Journal of Biomechanical Engineering - Accepted April 2018). Three additional manuscripts are under development. Nine presentations have been made at various conferences. Finally, a large grant has been submitted to CIHR and then converted into proposals to the St. Joseph’s Foundation and NSERC to continue to build on this work.

Birmingham, Trevor

Shoemaker, Kevin*

Al-Khazraji, Baraa

Health Sciences

Health Sciences

Health Sciences

Cerebrovascular Control in Osteo-Arthritis

Summary: The human musculoskeletal and cardiovascular systems enable mobility, independence, physical activity, and health. Yet, diseases of these systems create the greatest healthcare burdens in Canada and globally. The most common of these diseases, osteoarthritis (OA) and stroke, share several risk factors and comorbidities, but little is known about their shared disease mechanisms. The team’s overall objective was to better understand cerebrovascular health in patients with OA and, subsequently, address strategies for primary and secondary prevention. They compared OA patients, healthy controls, and patients with cardiovascular disease (CVD) but no OA, to: 1) quantify cerebrovascular reactivity to carbon dioxide and rapid transient reductions in arterial pressure; 2) assess circulating markers of chronic inflammation and vascular endothelium damage as well as flow-mediated dilation; and 3) measure polymorphonuclear neutrophil (PMN) rolling/binding in cultured human cerebrovascular endothelial cells using an in vitro bioassay with patient plasma. They found that patients with OA are at a higher risk of developing cardiovascular and cerebrovascular disease, and vascular health parameters in those with OA are similar to those with known CVD. Impact: The team plans to leverage the BJI catalyst support to: a) increase the sample size and confirm cerebrovascular problems identified in the current pilot, b) study underlying mechanisms of cerebrovascular and peripheral vascular responses (e.g., inflammatory pathways), and c) develop an exercise prevention program to improve cerebrovascular and peripheral vascular health outcomes. The results have been presented at 3 conferences and 1 manuscript has been submitted for publication (results pending). A grant proposal has been submitted to an external funding agency to support future studies (results pending).

Ardelean, Daniella*

Pope, Janet

Seguin, Cheryle

Schulich

Schulich

Schulich

Generation of Patient Specific Induced Pluripotent Stem Cells for Modeling Rheumatoid and Juvenile Idiopathic Arthritis

Summary: With a focus on modeling arthritis in children and adults in the laboratory, this project was well aligned with multiple Institute objectives and research areas. It prompted new collaborations with two academic investigators, one academic collaborator, and one community collaborator. The main outcomes of the study included: 1) the generation of multiple clones of induced pluripotent stem cells (iPSC) from four patients with rheumatoid arthritis and one control; 2) the identification of novel potential gene candidates for juvenile idiopathic arthritis (JIA) in 2 related children with JIA; and 3) the testing of prediction algorithms for variant analysis in polygenic diseases such as JIA. Impact: The team looks forward to building on this work to continue the characterization of iPSC from rheumatoid arthritis patients and to start the generation of iPSC in children with JIA as well as the testing of novel gene candidates in other children with JIA. The BJI funds that supported this project were leveraged to secure $3.5K from the Rare Diseases Foundation and a small laboratory space. The team plans to submit 2 publications regarding novel genes candidates in JIA and iPSC in RA and JIA. Results have been presented by the team trainee at regional and national conferences.

Chidiac, Peter

Getgood, Alan

Ramachandran, Rithwik*

Schulich

Schulich

Schulich

Exploring the proteinase activated receptor/TRPV4 signaling axis in Osteoarthritis

Summary: People with Osteoarthritis (OA) commonly experience pain and inflammation that negatively impacts their lives. A better understanding of pathogenic factors is crucial to guiding the development of new therapies that will not only manage symptoms, but also minimize progression of disease. Proteinase activated receptors (PAR) are G protein coupled-receptors (GPCRs) that are triggered following injury or infection. PARs stimulate cytokine production and leukocyte recruitment to the site of injury resulting in inflammation. Early results suggest that PAR activation sensitizes the mechanosensitive ion channel transient receptor potential vanilloid-4 (TRPV4), an important mechanosensor of the musculoskeletal system. Given that chondrocytes, osteoblasts and osteoclasts (cartilage and bone cells) all appear to express TRPV4 and members of the PAR family, the team aimed to examine the role of PAR activation in the regulation of TRPV4. Supported by catalyst funds, the team developed: 1) a highly sensitive biosensor for the detection of PAR activation by enzymes in biological fluids; 2) a transgenic mouse model for tissue specific deletion of TRPV4; and 3) a transgenic mouse to identify cellular location of TRPV4 expression. The team has also recruited knee OA patients to the study and obtained joint fluid to identify the presence of PAR activating enzymes. Early results have documented an abundance of PAR activating enzymes in the inflamed joint fluids and studies linking this activity to TRPV4 sensitization is ongoing. Impact: Future studies will assess whether mice with TRPV4 deletion in various musculoskeletal tissue are protected and whether activation of PARs exaggerates OA damage in relation to PAR sensitization of TRPV4 function. A post-doctoral fellow has been recruited to spearhead additional experiments needed prior to applying for external funding. Publications describing the biosensor and the transgenic mice are under development.

* nominated applicant/main contact person

Proposal Revision Requests

The Research Advisory Committee (RAC) acknowledges that innovative and early-stage MSK research projects occasionally face challenges that require a revision to the originally proposed project or team in order to meet the goals and requirements of the BJI Catalyst Grants Program.

APPLICABILITY: A formal revision request is required when a major change in direction is necessary or when changes in team composition (e.g. change in nominated applicant, disengagement of a crucial discipline expert) jeopardizes successful execution of a project. The goal of the revision request form and process is for RAC to determine if the revision is adequately justified and if appropriate risk management strategies are in place to maintain the current award. Minor changes in direction remain at the discretion of the investigator(s) in order to fulfill the overall goals of the proposed project (revision request is not necessary for minor changes).

ADJUDICATION: The Chair of the Catalyst Grants Program and two other members of RAC (selected by the Chair based on expertise and lack of conflict of interest) will review the request and adjudicate the revised proposal (possible outcomes: approved, approved with changes or denied). If denied or unable to address requested changes, RAC will encourage the team to apply to the next competition and instruct the team to return the unspent funds to the program.

INSTRUCTIONSPlease complete all sections of the form that are relevant to your request (require change from the original proposal) and submit a PDF version to Shannon Woodhouse at westerns.bji@uwo.ca. Shannon will forward the request to the current BJI Catalyst Grants Program Chair. The Nominated Applicant may be asked for additional information. Allow 4-6 weeks for a decision on your request.