Abstracts
News:
Oral Presentations - CBJC 2022
The following will be presenting their research in one of the following oral sessions at this year's conference. Congratulations to all those that have been chosen.
| AUTHOR* PAPER ID |
TITLE ABSTRACT |
| Thursday April 21st 12:45-2:15pm |
Plenary Session A: Inflammation & Autoimmune Diseases |
| Koudys, Zachary J* | Autoradiographic Measurement of [18F]FEPPA Uptake in Knee Synovial Tissue |
| 18 | BACKGROUND: The progression of osteoarthritis (OA) involves an inflammatory component affecting all joint tissues. Resident macrophages in the synovial lining play a critical role in maintaining synovial homeostasis and inflammation of the joint. Activated macrophages over-express the translocator protein (TSPO). [18F]FEPPA is a novel PET radiotracer for targeting expression of TSPO. RATIONALE: Therapies to modify the progression of OA have been largely unsuccessful, likely due to the advanced stage of the disease by the time clinical symptoms present. There is a need for non-invasive, in vivo imaging of active inflammation in knee tissues to better understand the early development of OA and study possible interventions earlier on in the disease. PURPOSE: To this end, the goal of this research is to investigate the relationship between [18F]FEPPA tracer uptake and the activated macrophage content of knee synovial tissue of patients with end-stage OA. METHODOLOGY: Knee synovial tissue samples from 4 OA patients undergoing total knee replacement (TKA) were sectioned and embedded on slides. Tissue sections were incubated in [18F]FEPPA for then imaged by autoradiography. To validate the tissue tracer uptake data, tissue sections were stained with H&E, TSPO, and CD68 and immunofluorescence was measured. Data sets were compared statistically to calculate p, and R2 values. RESULTS: [18F]FEPPA tracer uptake calculated from autoradiography was significantly correlated to the signal from TSPO immunofluorescence with p=0.002642 and R2=0.8. SIGNIFICANCE: [18F]FEPPA uptake corresponds to the presence of macrophages in knee synovial tissue taken from patients with end-stage OA. This result suggests that [18F]FEPPA PET may be an effective tool for evaluating the role of synovial inflammation in the progression of OA. Future clinical work will use this tracer to investigate the role of chronic inflammation in the development of fibrosis and stiffness after TKA. |
| Thavaratnam, Kabriya*; Gracey, Eric; Ratneswaran, Anusha; Vohra, Shabana; Lively, Starlee; Rockel, Jason; Dupont, Sam; Gandhi, Rajiv; Elewaut, Dirk; Kapoor, Mohit | Single nuclei RNA-sequencing identifies cell populations in OA synovium |
| 24 | Background: Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degeneration, subchondral bone remodeling, and synovial inflammation. The pathogenesis of OA is unknown and little research has been done on the synovium and to determine its implications in OA. Rationale: To delineate the synovium’s role in OA pathogenesis this study uses single nuclei RNA sequencing (snRNAseq), spatial transcriptomics, and functional assays. This study assesses synovium from early- and late-stage radiographic knee OA patients and uses an animal model to assess synovial function. Objectives: Hypothesis: SnRNAseq will identify distinct cell subsets in early and late stages of radiographic knee OA samples. 1: Identify distinct clusters of cells in the synovium from early vs late-stage knee OA. 2: Validate and localize the identified cell subsets in human OA synovial tissue. 3: Assess functionality of cell subtypes using in vivo murine model and human OA synovial tissue. Methods: Synovial tissue from early [Kellgren-Lawrence (KL) grade I; n=5] and late [KL grades III/IV; n=4] stage knee OA patients were subjected to snRNAseq and clustering analysis. Differential gene expression analysis identified representative genes for each cluster and are being validated using flow cytometry and immunohistochemistry. Spatial transcriptomics is being used in the destabilization of the medial meniscus (DMM) mouse model over time (naïve, and 5-weeks post-DMM) to explore the relationship between gene expression profiles and cellular localization. Results/ Significance: This study identified fibroblasts and macrophages to be the predominant cell type in the synovia and transcriptionally distinct subclusters of both cell types. Some subclusters were prominent in the early stage and others in the late stages of radiographic knee OA. Validation and functional studies are being performed to confirm the presence of these cells and delineate their roles in OA pathophysiology. |
| Ulanova, Sofya*; Cairns, Ewa; Barra, Lillian | T Cell Reponses to Homocitrulline in a Mouse Model Of Rheumatoid Arthritis |
| 37 | Background/Objective: Rheumatoid Arthritis (RA) is a chronic autoimmune disease that affects 1% of the global population and is characterized by inflammation in the joints. The most significant genetic risk factor for RA is the HLA-DR4 gene, which encodes Major Histocompatibility Complex Class II molecules containing the “Shared Epitope” (SE), a motif in the peptide-binding groove. Antigen-presenting cells expressing the SE can present citrullinated self-peptides to CD4+ T cells which leads to T cell activation, proliferation, pro-inflammatory cytokine release, and autoantibody production. It has been recently discovered that SE can also present homocitrullinated peptides. However, the phenotype of T cells activated in response to novel homocitrullinated peptides remains unknown. Methods: In this study, we performed T cell phenotyping in DR4-transgenic mice (tg) expressing SE in response to immunization with synthetic homocitrullinated peptide (HomoCitJED) developed by our laboratory. Male and female, 8-12-week-old, DR4tg mice (n=4-6 per group) were immunized with HomoCitJED or PBS. Spleens were collected and flow cytometry was performed to study T cell phenotypes. Results: Our preliminary results show a significant reduction of 22.5% (p<0.05) in the frequency of central memory T cells in HomoCitJED immunized mice at 30-days post-immunization, suggesting a potential shift to effector T memory cell phenotype. We also observed a 60% increase in T cells expressing the activation marker CD25, a 50% increase in Th2 cells, and an 85% increase in Th17 cells in HomoCitJED immunized mice compared to PBS controls (p<0.05) at 70-days post-immunization. Significance: We believe that determining the phenotypes of RA-specific T cells will help us understand immune responses to homocitrullinated antigens and will bring us one step closer to the development of immunomodulatory therapies targeting RA-specific T cells which will help RA patients live pain-free and high-quality lives. |
| Thursday April 21st 4:30-5:40pm |
Plenary Session B: Phenotyping, Context, and Design Principles |
| Le, Denise; Almaw, Rachel D*; Rinaldi, Daniel; Ivanochko, Natasha ; Harris, Sheereen; Benjamin, Ashley; Maly, Monica | Barriers/Strategies to Recruiting Visible Minorities in MSK Health Research |
| 34 | Purpose Musculoskeletal disorders (MSDs) are one of the leading causes of disability in Canada. Visible minorities (VM) are disproportionately affected by MSDs yet remain underrepresented in health research. Lack of representation in research reduces generalizability of findings and contributes to health disparities among VM. The purpose of this scoping review was to identify barriers and evidence-based strategies associated with increasing recruitment of VM in MSD research, from a Canadian perspective. Methodology Electronic databases (MEDLINE, EMBASE, CINAHL, and PsycInfo) were searched. Search strategies used terms related to the concepts of ‘race/ethnicity’, ‘participation’, ‘research’ and ‘musculoskeletal.’ Studies published from 1964-2021, that focused on MSD and addressed barriers/strategies for recruitment of VM were included. Two reviewers independently screened titles and abstracts, completed full-text reviews, and extracted data. Study characteristics and barriers/strategies to increasing participation of VM in MSD research were extracted and summarized. Results Of 4,282 articles identified, 28 met the inclusion criteria. Most included articles were from the United States. VM represented were Black, Hispanic/Latinx, Asian, Indigenous, Middle Eastern, and Multiracial. The most commonly identified barriers to research participation were mistrust, logistical barriers and lack of awareness/understanding of research. Strategies for increasing diversity included: ensuring benefit of participation, recruiting through sites serving the community of interest, and addressing logistical barriers. Significance Current literature lacks a Canadian context on improving diversity in MSD research. To reduce barriers to participation among VM, understanding and collaborating with racialized communities and addressing logistical barriers may be effective. This review presents strategies and a framework to aid researchers in increasing inclusion in MSD-related research. |
| Cherppukaran, Tanya J* | Validating a Screening Tool for Identifying Perpetrators of Violence |
| 32 | Background: Intimate partner violence (IPV) is the most common cause of nonfatal injury in women worldwide. Addressing IPV in the healthcare setting has previously focused on identifying and assisting survivors. However, the cause of IPV, the perpetrators, is often overlooked. Identifying perpetrators is the first step in challenging this issue. Current screening tools exist; however, the questions used are inappropriate for general screening due to excessive length, accusatory language, and a focus on quantifying the extent of a perpetrators’ violent behavior. Therefore, a brief screening tool with acceptable language would be invaluable in effectively identifying and assisting IPV perpetrators, ultimately reducing incidents. Specific Aims: This study compares a brief screening tool using patient-informed, non-accusatory questions against an existing validated measure of IPV perpetrator violence. Methods: This is a cross-sectional survey of male participants with acute injuries, assessed using our novel screening questions and an established measure of IPV perpetration (Conflict Tactics Scale 2). Two groups of patients will be recruited: those with hand fractures, believed to include a high prevalence of IPV perpetrators, and those with lower-body injuries, assumed to represent the background prevalence of orthopaedic trauma patients. A multivariate regression model will be developed to examine the relationship between IPV perpetration and answers to the screening questions. Anticipated Results: We hypothesize that our novel screening tool will effectively identify IPV perpetrators, and that the language proposed will be more acceptable than the current standard. Conclusion: There is a paucity of research on identifying IPV perpetrators in orthopaedic trauma or hand clinics. We will develop a screening tool to identify IPV perpetrators in a healthcare setting, thus allowing them to be guided towards education and treatment, helping stop the cycle of abuse. |
| Nematollahi, Shahrzad*; Dahan-Oliel, Noémi | Identifying Common Data Elements for an Arthrogryposis registry |
| 12 | Background: Arthrogryposis Multiplex Congenita (AMC) is a large group of congenital musculoskeletal (MSK) conditions characterized by joint contractures in two or more body parts. AMC management lacks data due to rarity and widely dispersed cases. Originality/Rationale: Expanding the AMC registry, currently in eight Shriners hospitals for Children in Canada and the US, to international scope requires consensus-based common data elements (CDEs) as a novel AMC terminology using multidisciplinary collaborations and patient engagement. Objectives: To identify consensus-based CDEs for an AMC registry, assess data necessity/ feasibility, and standardize data elements using the Human Phenotype Ontology (HPO). Methodology: This is an ongoing mixed-method study including focus group discussions (FGDs) and three rounds of Delphi survey recruiting clinicians and adults with AMC. 529 data elements are categorized by a tiered approach. Lawshe’s Content-Validity Ratio (CVR) is computed for consensus (accepted level>0.30). Findings: So far, two pre-Delphi FGDs (n=8;8) and round one of Delphi (n=42; 58% response rate) are completed. Participants were clinicians and lived experience from North America, Europe, and Australia. Of 529 elements, 156 (29%) were accepted, 49 (9%) were excluded, and 324 (61%) will be moved to round two for agreement. Core data elements will be classified to HPO terms. Significance/Impact: Various stakeholders including clinicians in pediatrics, medical genetics, orthopedics, occupational and physical therapy, and adults with AMC are involved. Familial clusters of AMC, pre-conception exposures, early life, and prenatal detection received the highest consensus suggesting important domains for future studies on rare MSK conditions. Standardized data collection using CDEs improves data efficiency by unifying data with substantial implications for new consensus-based guidelines for individuals with rare MSK conditions, such as AMC. |
| Ziebart, Christina*; MacDermid, Joy | An exercise and education program for adult’s post DRF |
| 9 | Purpose: Osteoporosis is a bone disease that increases the risk of fractures. In adults aged 50-65, a distal radius fracture (DRF), especially after a fall from level ground, can be the first sign of osteoporosis. Bone health is an important part of secondary fracture prevention and should address exercise, diet, and fall prevention including identification of fall hazards. This study reports the development and pilot evaluation of an online exercise and education bone health program for individuals after a distal radius fracture (DRF). Methods: A pilot randomized controlled trial (RCT) was conducted to see whether an online six-week whole body exercise and education program (Hands Up Program) is feasible, compared to usual care. The exercises include addressing lower body strength, upper body strength, hand therapy, and balance exercises prescribed at 3 sets of 8-12 repetitions. The educational modules focus on falls prevention, nutrition for osteoporosis prevention/recovery, and learning about osteoporosis. Participants engaged in the program online, twice a week for six weeks. Participants in the intervention group were then asked to participate in one-on-one interviews to assess the usability, engagement, and any feedback on the online program. Results: When approached to participate 67/122 (55%) agreed. Reasons for not participating included: being too busy to participate, not interested in the program, not willing to come into the hospital for the outcome measures or did not respond to the recruitment effort. Discussion: The online program allows for greater accessibility for people that may have to commute, live in rural communities, or during public health travel restrictions as compared to in-person group exercise program implementation.This study will show the results of participant adherence with the program and their feedback on what they positively responded to and what could be improved with the online platform. |
| Friday April 22 12:00pm - 1:30pm |
Plenary Session C: Juvenile Arthritis, Care, & Transitions |
| Battersby, Harry S*; Pamukoff, Derek; Garcia, Steven; Holmes, Skylar; Shumski, Eric; Heredia, Caitlyn | Influence of sex on gait and cartilage thickness after ACL reconstruction |
| 14 | Background: Female sex and traumatic joint injury are associated with higher risk for osteoarthritis (KOA), potentially via aberrant gait biomechanics. Purpose: The purpose was to assess the influence of sex on the association between the knee adduction moment (KAM) during gait and medial femoral cartilage thickness in a sample with ACL reconstruction. Methodology: Twenty-seven individuals with primary unilateral ACLR participated (12 males, 15 females; Age = 22.3 ± 3.8 years; BMI = 25.8 ± 6 kg/m2; Time since ACLR = 71.2 ± 47.2 months). While supine, participants were positioned at 90° and 140° of knee flexion. Ultrasound imaging was used to obtain medial femoral cartilage thickness. The superior and inferior borders of the femoral cartilage were manually segmented, and average thickness throughout the medial femoral condyle was used for analysis. Gait biomechanics were assessed over 5 gait trials along a 10m walkway. Marker trajectories were sampled at 240 Hz and force plate measurements were sampled at 2400hz. The external KAM was extracted using inverse dynamics and normalized to a product of body weight and height. Cartilage thickness of the injured limb was compared between males and females using 2 (position) by 2 (sex) ANOVA. The association between the KAM and cartilage thickness were explored using partial correlation adjusted for gait speed. Results: There was no position by sex interaction on medial cartilage thickness, but females had thinner medial cartilage thickness (1.96 (0.47) mm vs. 2.29 (0.29) mm, p=0.01). The KAM was associated with thinner cartilage when assessed at 90° of knee flexion in females (r=0.445, p=0.047), but not in males (r=-0.056, p=0.435) or at 140° of knee flexion in either sex. Significance: Females had thinner cartilage compared with males regardless of measurement position. The KAM, a surrogate of medial compartment knee loading, may be more relevant to females compared with males for post-traumatic KOA development after ACLR. |
| Maciukiewicz, Jacquelyn M* | Strengthening Improves Muscle Capacity Utilization in Women with Painful Knee Osteoarthritis |
| 8 | Background/Rationale:Deficits in peak knee extensor torque is a risk factor for the initiation of knee osteoarthritis (KOA) [1]. Strengthening exercise improves symptoms [2], but it remains unclear if biomechanical mechanisms contribute to this improved clinical status. Muscle capacity utilization, which reflects the proportion of maximum capacity required to complete tasks, may provide insight into how strengthening exercise improves clinical outcomes in painful KOA. Purpose: The purpose of this secondary analysis was to determine if strengthening reduces muscle capacity utilization during level walking and lunge tasks in women with painful KOA. Methodology:Data from 25 women with painful, clinical KOA were included in this secondary analysis. Participants completed a 12-week strengthening intervention [3]. Peak knee extensor torque was measured on a commercial dynamometer (Biodex System 3). Peak external knee flexion moment (KFM) during gait and a static lunge were measured using standard 3D motion analyses (Optotrak Certus, AMTI OR6-7). Muscle capacity utilization was the ratio of peak KFM to peak extensor torque. Paired t-tests were used to determine differences between peak extensor torque, peak KFM (gait/lunge) and muscle capacity utilization (gait/lunge) pre/post intervention (p<0.05). Results: Participants were 59.8 ± 6.3 years old and 30.5 ± 5.3 kg/m2 at baseline. Peak knee extensor torque increased at follow up, while both peak KFM and muscle capacity utilization during gait decreased (Table 1). Peak KFM and muscle capacity utilization during lunge remained unchanged. Significance/Impact: A reduction in muscle capacity utilization during gait indicates a decrease in relative effort. Importantly, we observed both an increased peak extensor torque and reduced peak KFM after strengthening, suggesting that strengthening both increases strength and decreases the net moment required (perhaps to stabilize the knee) during daily tasks in individuals with KOA. |
| Schulz, Jenna* | Changes in biological markers of knee inflammation after high tibial osteotomy |
| 13 | Purpose: Substantial changes in knee load produced by high tibial osteotomy (HTO) provide a model to explore the relationship between changes in knee load and inflammation. Therefore, the objective of this study was to investigate changes in joint pathophysiology by measuring broadly studied synovial fluid targets in osteoarthritis (OA) one-year after HTO. Methods: Twenty-six patients with varus alignment and symptomatic knee OA underwent synovial fluid sample collection prior to and one year after unilateral medial opening wedge HTO. These data were queried using gene set enrichment analysis (GSEA) via a two-group comparison and a leading-edge analysis was performed to identify top candidates enriched in numerous pathway sets. Also, linear mixed effects models (LMM) were performed on the individual biomarker concentration and FI data where timepoint (baseline and one-year post-HTO) was a fixed effect, and participant was a random effect. Results: There was negative enrichment post-HTO (i.e. higher at baseline) of several gene sets related to inflammation such as immune and leukocyte responses and signaling pathways as well as several gene sets related to regulation of anabolic processes such as of cell development and negative regulation of cell population proliferation. Leading edge analysis revealed that the highest contributors to negative enrichment post-HTO (higher at baseline) included inflammatory biomarkers such as IL-6, TNF-a and IL-8. Additionally, EGF, PDGF and FGF were identified as top positively enriched markers post-HTO. After adjusting for individual baseline differences LMM suggested MMP-3, TIMP-1 and IP-10 decreased after HTO whereas MMP-7, PDGF-AA and sCD40L increased after HTO. Conclusion: This study demonstrates that mechanically-driven inflammation can be converted to a pro-healing physiologic state with sufficient reduction in the mechanical load back to non-damaging levels. |
| Thursday April 21st 2:25-4:20pm |
Special Emphasis Session Basic Science for MSK |
| Bader, Taylor J*; Dhiman, Manmeet; Salo, Paul; Duncan, Neil; hart, David; Swamy, Ganesh | Do Changes in Degenerated Intervertebral Discs Result in Spinal Deformity? |
| 30 | Introduction Intervertebral disc degeneration (IVDD) is age-related break-down of the tissue leading to structural failure of the disc. The degradative changes to the structure of degenerated IVDs (degen) can result in back pain or radicular pain due to impingement of nerve roots. Some patients develop malalignment of the spine, in the sagittal plane (degenerative spondylolisthesis (dSpondy)) or in the coronal plane (degenerative scoliosis (dScoli)). These painful conditions significantly impact the patient’s quality of life. The aim of the present study was to measure elastic and viscoelastic shear properties, characterize tissue organization, and measure biochemical differences between normal and patient samples of the annulus fibrosus (AF). We hypothesize that a reduction in shear stiffness of the AF may cause the development of the spinal deformities dSpondy and dScoli. Methods Samples included both L4-5 and L5-S1 from patients undergoing anterior and lateral degen/dSpondy/dScoli surgeries. Mechanical testing of 5mm3 AF tissue cubes was performed using shear loading. Mechanical tests deformed the AF to 10% and 40% strain. Tests were performed in both the radial and circumferential direction, mimicking shear deformation seen in dSpondy and dScoli. Results At 10% strain the circumferential shear modulus of degen AF samples was 69.7±16.1 kPa (n = 11) compared to 20.6±12.1 kPa (n = 11) in the deformity AF (p<0.01). Interestingly, the radial shear modulus of degen AF samples was 22.5±24.3 kPa compared to 12.9±11.1 kPa in the deformity AF (p=0.15). Similar trends were present at 40% strain. Conclusions These preliminary results suggest that deformity AF is less stiff than non-deformity, degenerated AF. Over the next six months, we anticipate collecting 60 more surgical samples and include 20 normal samples as controls in our final analysis. Biochemical and histological assessments will aim to distinguish between cause and effect and determine underlying mechanisms. |
| Dabbagh, Armaghan*; MacDermid, Joy; Yong, Joshua; Packham, Tara; Macedo, Luciana; Boutsikari , Eleni | Diagnostic accuracy of provocative maneuvers for the diagnosis of carpal tunnel syndrome: a systematic review with meta-analysis |
| 5 | Objective: To summarize and evaluate the evidence on the accuracy of provocative maneuvers used to diagnose carpal tunnel syndrome (CTS). Design: Systematic review with meta-analysis Methods: We searched MEDLINE, CINAHL, Cochrane, and Embase, selecting studies that assessed at least one diagnostic accuracy property of the provocative tests for CTS diagnosis. We extracted study characteristics and any information on the diagnostic accuracy of the provocative tests for CTS. We conducted a random-effects meta-analysis of the Phalen’s test and Tinel’s sign. We rated the risk of bias (ROB) using the QUADAS-2 tool. Results: We included 31 studies, assessing 12 provocative maneuvers. Phalen’s test and Tinel’s sign were the two most assessed tests, respectively, in 22 and 20 studies. The ROB was unclear or low in 20 studies, and at least one item was rated as having high ROB in 11 studies. Phalen’s test had a pooled sensitivity of 0.57 (95% CI 0.44- 0.68; range 0.12- 0.92), and a pooled specificity of 0.67 (95% CI 0.52- 0.79; range 0.30- 0.95). For the Tinel’s sign, the pooled sensitivity was 0.45 (95% CI 0.34- 0.57; range 0.17- 0.97), the pooled specificity was 0.78 (95% CI 0.60- 0.89; range 0.40- 0.92). Other provocative maneuvers were less frequently studied and had more conflicting diagnostic accuracies. Conclusions: There was low and unclear ROB evidence that Phalen’s test and Tinel’s sign are moderately accurate in diagnosing CTS. Clinicians should consider combining provocative maneuvers with sensorimotor tests, hand diagrams, or questionnaires for the highest accuracy, before referring to more invasive diagnostic methods. |
| Maglaviceanu, Anca*; Rockel, Jason; Wasilewski, Ewa; Lewis-Bakker, Melissa; Filippini, Helena; Bonin, Robert; Leroux, Timothy; Clarke, Hance; Kotra, Lakshmi; Kapoor, Mohit | The effects of Δ9-tetrahydrocannabinol (THC) on osteoarthritic joint cells |
| 6 | Background & Rationale Patients with osteoarthritis (OA) use cannabis products to reduce chronic joint pain. However, little research exists on the effects of cannabinoids on OA pain and disease pathogenesis. Our pre-clinical results suggest that oral delivery of 7.35 mg/kg Δ9-tetrahydrocannabinol (THC) reduces pain and joint degeneration in mouse models of OA. THC signals through CB1 and CB2 receptors that are expressed on OA chondrocytes and fibroblast-like synoviocytes (FLS), reducing intracellular cAMP levels. Purpose I am interested in elucidating the effects and mechanisms of action of THC on human OA FLS and chondrocytes in vitro and their pathophysiological function in the context of OA. Methodology FLS and chondrocytes were isolated from OA synovium and cartilage samples, respectively, obtained from patients undergoing total knee arthroplasty. Trypan blue exclusion, flow cytometry, and enzyme immunoassays were used to quantify cytotoxicity, Annexin V+ cells, and CB1/CB2-modified cAMP levels, respectively, in OA FLS and chondrocytes treated with THC (0-36.75 µM in 0.5% DMSO) for up to 48 hours. CP-55940 (CB1 and CB2 agonist, 10µM) was used as a positive control in cAMP assays. RNA sequencing coupled with bioinformatics, Nanostring validation, and functional assays will further reveal the signaling mechanisms of THC in joint cells. Results OA FLS (n=6) survival significantly declines at ≥11 µM THC by trypan blue exclusion, while concentrations as low as 1.84 µM and 3.68 µM significantly increase Annexin V+ FLS (n=6) and chondrocytes (n=4), respectively. Additional flow cytometry experiments are underway to increase the chondrocyte sample size. cAMP assays have been initiated to optimize the THC concentration for future RNA sequencing experiments. Significance Future RNA sequencing analyses will potentially reveal the mechanisms of action of THC on joint cells during OA, which may give us some insight into its therapeutic potential. |
| Norman, Elizabeth*; Suh, Nina; Lalone, Emily | Provocative Scapholunate Instability Wrist Positioning |
| 4 | INTRODUCTION: Scapholunate (SL) instability is the most frequent type of carpal instability. Injuries to the SL ligament result in a widening of the space between the scaphoid and lunate (diastasis) that is measured clinically using radiographs. Early SL tears are often missed and lead to the development of SLAC (scapholunate advanced collapse), a leading cause of wrist arthritis. The objective of this study is to employ stressCT to image patients who have suffered an SL ligament tear to examine pathomechanics. METHODS: In this parametric study, three SL patients were recruited and underwent stressCT (four-dimensional computed tomography (4DCT)) scanning at our facility. Through the motion of radial/ ulnar deviation we obtained CT images of the wrist in radial, ulnar, and kinematic neutral positions. In addition, static scans were taken with the wrist neutral position and neutral clenched fist position. 3D models of the scaphoid, lunate, capitate, and radius were created using 3D Slicer. Next, contact maps were created from these models, between the scaphoid and lunate (scapholunate gap) and the capitate and radius (radiocapitate gap). RESULTS SECTION: First, when examining the minimum distance between the scaphoid and lunate the distances vary with wrist position indicating that this injury is dynamic and for proper injury detection alignment is very important. In addition, the minimum distance between the radius and capitate decreases when in a clenched fist position when compared to the neutral positions. DISCUSSION: These preliminary results show how the minimum distance is affected based on the positioning of the wrist. The results show that the capitate becomes closer to the radius and this indicates that as the wrist is clenched the capitate becomes closer to the scaphoid and lunate and ultimately could shift these bones outside of their normal location. This results in degradation of the surrounding bones and could lead to SLAC arthritis. |
| St-Pierre, Marc-Olivier *; Effatparvar, Mohammad Reza; Begon, Mickaël; Sobczak, Stephane | Strains variations within the ilio-femoral ligaments during hip motions |
| 26 | Background Strains in the iliofemoral ligament have been assessed using a single strain gauge placed in its mid-portion, limiting the information taken in the entire length of the ligament.1, 2 Originality This is the first study to assess strains within the two bands of the iliofemoral ligament during hip motions using a segmental approach and no tool inserted in the ligament. Purpose Report strains in the medial (MIFL) and lateral (LIFL) bands of the iliofemoral ligament and their proximal, mid- and distal portions. Methodology 10 hips were harvested and all muscles were removed. Eight and ten 2-mm plastic hemispherical markers were glued on the lateral and medial borders of both bands (Figure 1). Four positions were assessed (end-range ROM): abduction (ABD), extension (EXT), internal (IR), and external (ER) rotations, both combined with EXT. Strains were measured from the anatomical position (ANAT). A scanner (Laser HP-L-8.9 T2, Hexagon, Stockholm, Sweden) helps determine the marker’s 3D position. Strains were compared with a three-factor ANOVA (Bonferroni posthoc test) (movement, borders, portions). Figure 1. Location of the hemispherical markers. (A) anterior view. (B-C) Portions of the lateral and medial borders of the LBIFL and MBIFL. (D) Anterior Hip 3D scan in anatomical position. Results Strains in the MIFL during IR showed no change compared to ANAT (p = 1.00). ABD showed differences in strains between borders with the lateral borders showing fewer strains (p = 0.001). In the MIFL, the mid- portions have shown the greatest strains for both borders (p < 0.05). In the LIFL, the distal portion showed the greatest strains in ABD, EXT, and ER (p < 0.05). Discussion Strains varied between the portions and significantly different strains were observed in ABD between borders. This 3D scanning technique helps to precisely assess regional strains in each ligament and might be transferred to other ligaments. |
| Straatman, Lauren*; Walton, Dave; Lalone, Emily | The Exploration of the Relationship between Kinematic Joint Contact and Subchondral Volumetric Bone Mineral Density |
| 2 | Pain and disability following wrist trauma are highly prevalent, however the mechanisms underlying these outcomes are unknown. The purpose of this study is to explore the impact of kinematic joint contact on the underlying subchondral bone, to better understand potential mechanisms underlying pain and disability following wrist trauma. All participants (n = 5) underwent 4DCT scans while performing maximum flexion to maximum extension to estimate radiocarpal (specifically, radiolunate (RL) and radioscaphoid (RS)) joint contact area (JCa). The participants also underwent a static CT scan accompanied by a calibration phantom with known material densities that was used to estimate subchondral vBMD of the distal radius. Joint contact is measured by calculating inter-bone distances (mm2), and subchondral vBMD is presented using mean vBMD (mg/K2HPO4) at three normalized depths from the subchondral surface (0 to 2.5, 2.5 to 5 and 5 to 7.5 mm) of the distal radius. Pearson’s correlation coefficients were used to demonstrate the strength of the relationship between vBMD and JCa for all layers and both the RL and RS articular surfaces. Our results demonstrated a strong, positive relationship between JCa and subchondral vBMD during extension in the RS joint in the middle (2.5 to 5mm) and deep (5 to 7.5mm) layers of vBMD, r = 0.89, p = 0.04, and r = 0.91, p = 0.04, respectively. This indicates that in the RS joint during extension specifically, as JCa increased, vBMD also increased. The relationship between JCa and vBMD in the RL during flexion and extension, as well as the RS during flexion, was not significantly correlated. Within our study sample, subchondral vBMD is most impacted in the RS joint during extension. When coupled with changes to depth-specific layers of subchondral bone, the relationship between altered joint contact or joint loading and vBMD may demonstrate a more robust explanation for lasting pain and disability following wrist trauma. |
| Toor, Jaspreet*; Ulanova, Sofya; Blackler, Garth; Cairns, Ewa; Barra, Lillian | Citrulline and Homocitrulline Responses in a Model of Rheumatoid Arthritis |
| 23 | Over 1% of Canadians suffer from rheumatoid arthritis (RA), a chronic autoimmune disease that causes pain, swelling and damage within synovial joints. RA is characterized by autoimmune responses against post-translationally modified proteins, such as citrullinated proteins which have been extensively studied in RA. Up to 80% of patients express anti-citrullinated peptide autoantibodies (ACPA) and they have been shown to be pathogenic in commonly used RA models, including collagen-induced arthritis (CIA). In contrast, responses against proteins containing another post-translational modification known as homocitrullination are poorly understood, although >50% of RA patients also produce anti-homocitrullinated peptide autoantibodies (AHCPAs). This study was conducted to investigate immune responses to citrullinated and homocitrullinated peptides in the CIA model of human RA. Male, 8-12-week-old, DBA/1J mice (N = 18) were immunized with type II collagen emulsified in complete Freund’s adjuvant to induce arthritis and sacrificed 50 days later. ACPA and AHCPA IgG titres were measured via direct ELISA, using serum collected every 14 days until sacrifice. Spleens were isolated at sacrifice and T cell recall responses were measured using the CellTrace Violet flow cytometry proliferation assay. Our preliminary results show that T cell recall responses against a citrullinated peptide developed in 3 of 4 mice tested. Interestingly, all 4 mice tested also developed recall responses against a homocitrullinated peptide, a novel finding that increases the clinical relevance of the CIA model. This study helps characterize immune responses in the CIA mouse model of human RA to confirm its utility in future pre-clinical trials of RA-specific therapeutics. |
| Umoh, Joseph U.* | The Comparison of the Micro-CT Anatomical Measurement of the Cervical (C3 - C7) Vertebral Endplates in Human and Kangaroo |
| 48 | Introduction: The cervical endplates protect the disc and keep the vertebrae from fracture. Accurate dimensions of the endplate help in the design of cervical disc prostheses (used in the treatment of cervical degenerative disease), and in the modelling of the cervical vertebrae to show their biomechanics and susceptibility to injury. Interest in kangaroo as a model of human cervical spine is based on kangaroo’s pseudo-biped nature and relatively easy availability. The objectives of this study are to create a database of anatomical parameters of human and kangaroo cervical (C3 - C7) vertebral endplates, using micro-CT and to compare the human and kangaroo datasets. These data could be used to explore using kangaroo as a model of human spine biomechanical experiments in vitro. Methods: Five human cadaveric and five adult kangaroo cervical spines were imaged on a micro-CT scanner (GE Locus Ultra), with an x-ray tube voltage of 80 kV, a tube current of 55 mA, and a 3D-reconstructed image-volume voxel of 154 μm. The anatomical endplate superior width (EPSW), length (EPSL), and depth (EPSD); and endplate inferior width (EPIW), length (EPIL) and depth (EPID) were measured for each human and kangaroo vertebra. Results: In human, endplates EPIW are wider at the inferior surface than they are at the superior surface, EPSW. The opposite is true for kangaroo. EPSL was longer than EPIL in kangaroo. EPSW and EPSL decrease from C4 and C7 towards C5 in both human and kangaroo. Conclusions: Human and kangaroo cervical endplate data have been created. The endplate superior surface is concave (transversely) while the inferior surface is convex (laterally) for both human and kangaroo. C5 appears to have a smaller superior length and width. Initial investigation on the comparison between human and kangaroo cervical (C3-C7) vertebral endplates shows that both have similar shape but different structures. |
| Thurday April 21st 2:25-4:20pm |
Special Emphasis Session Human & Technology Interaction for Health |
| Baronette, Rudy*; Atkinson, Hayden; Teeter, Matthew; Holdsworth, David W | A deep learning-based approach for automatic knee bone segmentation |
| 22 | Osteoarthritis (OA) is a progressive degenerative joint disease estimated to affect 1 in 6 Canadians over the age of twenty, with knee OA being the most commonly affected joint. Bone shape, joint space, triplanar alignment, and osteophyte size and location are bony imaging biomarkers that are relevant to onset and progression of knee OA. Magnetic resonance (MR) imaging can produce 3D morphometric bone biomarkers to investigate early detection and develop effective treatments without ionizing radiation. Manual segmentation as the gold standard will become unfeasible for a large clinical dataset involving multiple imaging timepoints. The benefits of time saved and ability to analyze larger datasets via efficient automated segmentation likely outweigh the small advantage in precision that manual segmentation offers. To address this limitation, we trained a convolutional neural network (CNN) to automatically segment bony anatomy from knee MR images, based on a 3D generative adversarial network (GAN). Our dataset consisted of 245 knee MR volumes that were used to train a 3D GAN for 28 epochs. All volumes underwent random image augmentation consisting of gaussian noise, horizontal flips, vertical flips, and rotations (± 5°) to increase regularization and reduce overfitting. The training, validation, and test datasets were created using a 70/15/15 split, respectively. Performance was evaluated using Hausdorff distance and dice score. The network was evaluated on the test dataset (n=36) which had an average 95% Hausdorff distance of 1.46 mm and 0.967 dice score. Our proposed method had similar performance on both metrics when compared to previously published deep learning algorithms. We present a deep learning-based approach to efficiently segment bony knee anatomy from MR images. This method allows for rapid segmentation of labelled bony anatomy in larger clinical studies involving MR imaging assessments of knee OA. |
| Daemi, Parisa*; Zhou, Yue; Naish, Michael; Price, Aaron; Trejos, Ana Luisa | Kinematic Model of a Cable-driven Wearable Tremor Suppression Glove |
| 35 | Tremor, one of the most disabling symptoms of Parkinson's Disease, significantly affects the lives of people with Parkinson’s (PwP). For those suffering from hand tremor, wearable devices have been proposed to reduce tremor motion. The limited space surrounding the human hand and the balance between positioning accuracy, compactness, and weight have been shown to be the main challenges in the design of wearable devices for the hand. Cable-driven transmission systems have been proposed as a way to decrease the size and weight of these devices; however, they have complex control system requirements due to their substantially nonlinear behaviour. To solve the problem, this work aims to derive a comprehensive kinematic model of a cable-driven wearable tremor suppression device. It consists of kinematic equations that calculate the cable length as it moves through a sheath during hand flexion–extension motions. These equations consider the bone geometry of the hand joints and the characteristics of the glove design. The derived kinematic equations were verified through both simulation and benchtop experiments during single-joint and multi-joint movements. The kinematic model shows a mean Pearson correlation coefficient of 0.96 ± 0.01. To demonstrate the accuracy of the proposed method, the new model was compared experimentally to the Euclidean-norm model most commonly used, resulting in a root mean square error 9–22% lower with the proposed model. The statistical analysis showed that the experimental results were a highly significantly better match to the results of the proposed model, especially as the cable displacement increases. Thus, the derived comprehensive kinematic model can support the design of cable-driven wearable devices to avoid slack in cables and guide the optimal placement of sheaths. |
| du Toit, Carla*; Dima, Robert; Papernick, Sam; Fenster, Aaron; Lalone, Emily | 3DUS for Assessment of Synovitis in Basal Thumb Osteoarthritis Patients |
| 41 | Background: First carpometacarpal (CMC1) osteoarthritis (OA) is one of the most common sites of OA and is the cause of pain and disability for many patients. Current clinical diagnosis and monitoring of CMC1-OA disease are primarily aided by X-ray radiography; however, many studies have reported discrepancies between radiographic evidence of CMC1 OA and patient-related outcomes of pain and disability. Three-dimensional ultrasound imaging may be an option to address the clinical need for a rapid and safe point of care imaging device. Rationale: The purpose of this research project is to validate the use of mechanically translated 3D-US in CMC1 OA patients to assess the measurement capabilities of the device in a clinically diverse population in comparison to MRI. Methods: 10 CMC1-OA patients were scanned using the 3D-US device, which was attached to a Canon Aplio i700 US machine with a 14L5 linear transducer that had a 10MHz operating frequency and 58mm. Complimentary MR images were acquired. The volume of the synovium was segmented from both 3D-US and MR images by two raters and the measured volumes were compared to find volume percent differences. Paired sample t-test were used to determine any statistically significant differences between the measurements observed by the raters and in the measurements found using MRI vs. 3DUS. Interclass Correlation Coefficients were used to determine inter- and intra-rater reliability. Result: The mean volume difference between 3DUS and MRI was 1.78%. Synovial tissue volume measurement Standard Error Mean (SEM) was 11.21 mm3 and 46.63mm3 for 3DUS and MRI, respectively. The Minimal Detectible Change (MDC) was 31.06 mm3 and 46.63 mm3 for 3DUS and MRI. Excellent inter- and intra-rater reliability was observed across all imaging modalities and raters. Significance: This novel application of 3DUS would provide clinicians with an easy and efficient method to quantitatively measure and monitor OA progression at a patient’s bedside. |
| Koubaa, Nesrine*; Laprise, Simon; Brière, Simon ; Léonard, Guillaume; Boissy, Patrick | An intelligent sit stand desk to improve postural hygiene of office worker |
| 47 | Context: Computer Office work exposes employees to prolonged periods of static posture (PPSP) that can cause musculoskeletal discomfort (MSD). Sit stand desks (SSD) promote posture variation but they are not effectively and sustainably used. Originality: An Intelligent SSD, equipped with sensors to automate posture changes, was invented by our group. Purpose: Investigate the effects and acceptability of iSSD on postural hygiene and work conditions of office workers. Methods: 10 office teleworkers were recruited from the community to an n of one trial mixed study to use the iSSD over 65 cumulated working days. The study was comprised of 3 phases: A1, baseline with iSSD used in sitting position only; B, automated iSSD that imposed posture changes according to a fixed time of sitting and standing position, A2, iSSD not automated and position changes are initiated by the user. The sitting time (ST) and PPSP were continuously recorded by the iSSD sensors. MSD and work ability (WAS) were assessed by questionnaires at the start of study (T0) and at the end of phase B (T1) and A2 (T2). iSSD acceptability was explored through interviews at T1 and T2. Results: At T1 , the mean ST was reduced by 28.7% from T0 and no PSPP were observed. At T2, ST increased by 20% and PSPP counted for 26.5% of the workday when compared to phase B. Alleviations in MSD symptoms in the neck, shoulders, and lower back were observed from T0 after iSSD use (T1) and were maintained at T2. The mean WAS score did not change across the 3 measure times. Qualitative analysis of the interviews confirmed the potential of iSSD as a major facilitator to improve postural hygiene . Future studies: Further experimental studies on a larger sample over a longer follow-up time is needed. User compliance and acceptability of the automated iSSD and the subsequent improvements suggest that such approach could be leveraged to improve effective and sustainable use of SDD and reduce MSD during computer office work. |
| Kwan, Jan* | Thermo-Responsive Coatings for Treating Infection at Orthopedic Implants |
| 10 | Background and rationale Orthopaedic surgical infections are an ongoing challenge. They are particularly difficult to treat because they frequently involve bacterial biofilms on metal implants. Treatments often involve multiple surgeries to replace the infected component, which are expensive and sometimes ineffective. Antibiotic-containing bone cement or other carriers have shown promise, but do not release the drug in a controlled manner and the release is often too slow or too rapid. Objective The aim of this study is to develop a drug-eluting polymer coating for metal implants that can be thermally triggered by magnetically induced heating of the metal implant to release antibiotics rapidly on demand. Methods A biodegradable poly(ester amide) (PEA) with a glass transition temperature of ~39 °C was prepared. Coatings were prepared by codissolving rifampicin and PEA and then spraying the solution onto titanium alloy discs. In vitro drug release was performed using continuous heating at set temperatures (50 – 80 ℃) or inductive heating at 123 kHz to 50 ℃ intermittently with 6 min intervals for 1 h. Drug release was assessed in phosphate buffered saline using UV-visible spectroscopy. Staphylococcus (S.) aureus at 105 colony forming units/mL was used for biofilm formation, and the biofilm was quantified using crystal violet staining. Results and significance Drug release from rifampicin-loaded coatings was successfully triggered by either direct or magnetically induced heating, while maintaining the surrounding solution temperature at 40 ℃ or less, to minimize potential tissue damage. Heating or antibiotic-loaded coatings alone individually reduced S. aureus biofilm formation by 50% and 36% respectively, but the combined use of both therapies reduced biofilm by 95% showing a potential synergistic effect. This new technology provides a promising new approach to potentially prevent and treat implant-associated orthopaedic infections. |
| Rier, Elyse*; Wohl, Gregory | Interactive Segmentation of 3D Bone Models Generated Using 3D Point Clouds |
| 29 | Computed Tomography (CT) images are used to visualize internal structures due to their high geometric truth. These are then used to create 3D models of anatomical areas of interest for surgical planning and designing implants. The rationale of this project is to create a platform to allow individuals to generate models of bone to create customizable implants. We developed a custom add-on in Blender that extracted bone from CT images as a 3D point cloud, converted the point cloud into an STL file, and allowed the user to extract a desired portion as a separate 3D model. Python was used to develop an add-on in Blender to manipulate CT data of a skull. The add-on imported the CT data, extracted a 3D point cloud representing the bone in the images based on a threshold, and then created an STL. The point cloud was created by applying a global threshold to segment the bone followed by a Canny edge detector to isolate the surface of the bone. Pixels representing the surface of the bone were given spatial coordinates based on pixel location: in-plane pixel spacing (x and y) and the slice location of the original CT images (z). The point cloud was transformed into an STL mesh with a 3D Delaunay triangulation from the Python package PyVista. The custom Blender add-on was able to create a 3D mesh model of the skull from a CT dataset, which was saved as an STL file. The mesh was used to visualize the skull and extract a region of interest using simple selection drawing tools in Blender. The extracted model maintained the shape of the selected region and preserved the curvature of the bone from which it was selected. An STL file of the selected region could then be exported and used for 3D printing. Future work in this project will involve validating the generated 3D models. This will involve comparing measurements on a physical object to the STL file that is extracted and 3D printed. |
| Tawiah, Andrews K*; Woodhouse, Linda; Wieler, Marguerite | Competency framework for advanced practice physiotherapy |
| 31 | Background: Advanced practice physiotherapy (APP) is an innovative model of care designed to address high volume of patients, reduce wait times and contain costs. Although APP is expanding, there is no standardized competency framework to support the training of practitioners. Rationale: The lack of a standardized competency framework has resulted in inconsistencies in the training of practitioners, which affects how patients and other healthcare professionals understand APP. Purpose: To develop a competency framework for the standardization of the APP model of care Methodology: Three studies were conducted. Study 1 was a scoping review of the available literature, which led to developing the 1st draft of competencies. Study 2 was a qualitative study with four focus groups using a qualitative descriptive approach to get feedback on the 1st draft and develop the 2nd draft of competencies. Study 3 was a cross-sectional online survey to validate the 2nd draft of competencies. Subject matter experts further reviewed the competencies developed from each study. Results: In study 1, 19 documents were retrieved with 13 reports and 6 research papers from the UK, Canada, Ireland, Australia, and New Zealand, resulting in 27 competencies. In study 2, 16 participants from the same countries participated in the focus groups. Five themes were developed (Clinical expertise, experienced communicator, strong leadership skills, collaboration, and knowledge creation & dissemination), resulting in a second draft with 24 competencies. Ninety-nine participants from the same countries completed the survey in study 3. All the competencies were validated and included in the final competency framework. Significance: These competencies developed from this study could serve as a standardized set of global competencies that different countries can adopt and adapt to meet their local needs. These competencies could lead to standardization of the training of practitioners. |
| Vakili, Samira*; Lanting, Brent; Getgood, Alan; Willing, Ryan | Development of Multi-Bundle Virtual Ligaments to Simulate knee Biomechanics |
| 16 | Purpose: Preclinical testing of total knee replacement (TKR) implants is essential to understanding their mechanical performance and developing strategies for improving joint stability. The purpose of our study was to determine if subject-specific virtual ligaments accurately reproduce the same behavior as real ligaments surrounding TKR implants on a joint motion simulator. Method: Five cadaveric knee specimens with TKR were mounted to a motion simulator. Each was subjected to flexion-extension (FE) and tests of anterior-posterior (AP), internal-external (IE) and varus-valgus (VV) laxity. Tibiofemoral kinematics were recorded during each motion. The forces transmitted through major ligaments (medial, lateral and the posterior cruciate ligament) were measured using a sequential resection and superposition technique. Ligament lengths were calculated based on the point-to-point distances between the femoral and tibial insertions. Ligament properties (stiffness, slack length) were calibrated by tuning the measured ligament force to a nonlinear force–length relationship. Based on this, virtual ligaments were developed for each specimen and were used to simulate the soft tissue envelop around isolated TKR implants mounted on the motion simulator. The same motions were then repeated. Results: The mean difference between virtual and native ligament knee kinematics during FE were below 3 mm for AP displacement, 2° for IE rotations, and 2° for VV rotations. The RMSE between virtual and native ligament knee laxities were 3.6 mm for AP, 8° for IE, and 2° for VV. Conclusion: In this study, virtual ligament properties were calibrated to best match native ligament behaviors. When used to stabilize isolated implants, the resulting behaviors were comparable to those of the real ligaments. These results suggest that databases of subject-specific knee ligaments could be developed and employed on joint motion simulators to simulate prosthesis behaviors in a large population of knees. |
| Friday April 22nd 1:35-2:15pm |
Special Emphasis Session: Basic Science for MSK |
| Chakraborty, Aishik*; Paul, Arghya | Nanoparticle-infused tough natural polymeric scaffold for bone regeneration |
| 42 | Background: The standard approach for healing fractures includes (a) bone transplantation, (b) application of drugs, and (c) fixation with medical implants. However, such procedures often lead to poor vascularization, damage to soft tissues, formation of bone defects, and poor on-site drug retention. These complications have led to innovations in alternative approaches where biomaterials are being considered for bone regeneration. Rationale: Natural, polymeric, water-retaining hydrogels have gained traction as a platform for healing fractures. However, natural hydrogels have small void spaces and weak mechanical properties, leading to poor cell infiltration and early degradation. Objective: To prepare scaffolds with large void spaces and superior strength. Here, we added multifunctional silica-based nanoparticles to the scaffolds to (a) improve their mechanical stability and (b) provide innate bone regenerative property. Fabrication: The scaffolds were fabricated by chemically connecting the polymers at sub-zero temperatures. This procedure, called cryogelation, formed ice crystals inside the scaffolds. Upon thawing, the ice melted to leave large void spaces. Characterization: The mechanical properties were evaluated with a dynamic mechanical tester and a rheometer. The shapes of the void spaces were observed by electron microscopy. The rate of degradation was determined in aqueous media. Lastly, the cytocompatibility was tested in vitro. Results: By adding the nanoparticles, mechanically tough polymeric scaffolds with large void spaces and reduced degradability were synthesized successfully. The scaffolds proved to be cytocompatible with red blood cells and endothelial cells. Significance and future studies: The designed scaffolds are particularly suitable for healing non-load-bearing bones and coating medical implants. However, the ability of the scaffolds to promote bone regeneration must be proved both in vitro and in vivo before further consideration. |
| Hitchon, Sydney*; Milner, Jaques; Holdsworth, David W; Willing, Ryan | Effect of Porous Shoulder Implant Stems in Different Bone Densities |
| 17 | Background/Rationale: Orthopaedic device-related infection often leads to two-stage revision surgeries – implantation of an antibiotic spacer to clear the infection and a second surgery to install a permanent implant. A permanent porous implant, that can be loaded with antibiotics, could allow for single-stage revision surgery. Gyroid structures can be constructed with high porosity, without stress concentrations that can develop in other period porous structures [1] [2]. Purpose: This research studies the viability of porous stems for implantation in three proximal humeri with varying bone densities, using finite element models (FEM). Methods: Porous humeral stems were constructed in a gyroid structure at porosities of 60%, 70%, and 80% using computer-aided design software. The stems were assumed to be made of titanium (Ti6Al4V). Three different bone densities were investigated, representing a healthy, osteopenic, and osteoporotic humerus. The strain energy densities within the proximal humeri and the stress distributions on the stems were analyzed using FEM. Results: Analysis of the strain energy densities within each bone density shows the porous stems do not cause further bone resorption than solid stems. In the osteoporotic bone, a decrease in bone resorption is observed as stem porosity increases. With the exception of a few mesh dependent singularities, all porous stems show maximum stresses below the yield strength of Ti-6Al-4V (880 MPa) [3]. Significance: The results of this study indicate these porous stems will not increase the stress-shielding effects often caused by solid stem implants and for osteoporotic bone, may reduce bone resorption. It is also indicated that these porous stems have adequate strength for implantation. These results show promise for replacing two-stage revision surgeries with a single revision surgery. Further research will include fatigue analysis of these porous implants, but current results do not predict catastrophic failure. |
| Polla Ravi, Shruthi*; Shamiya, Yasmeen; Coyle, Ali; Chakraborty, Aishik; Paul, Arghya | Cell-Derived Nanoparticles for Drug Delivery for Bone Repair Applications |
| 19 | Background and Rationale: The successful repair of bone defects is enhanced by the delivery of osteoinductive factors that promote the osteogenic differentiation of stem cells into bone cells. Nanoparticle delivery systems enable the sustained release of these factors but suffer from limitations such as biocompatibility and nanotoxicity issues, poor loading capacity, and poor cellular uptake. Cell-derived nanoparticles (CDNs) are produced from cell membranes. They offer unique advantages: high biocompatibility, increased cellular uptake, and high drug loading efficiency. These properties could allow for a sustained release of osteoinductive factors entrapped within the CDNs for bone regeneration. Objectives: a) To prepare, optimize, and characterize CDNs loaded with drug (osteoinductive) molecules, b) To establish the biocompatibility and biofunctionality of drug-loaded CDNs for the osteogenic differentiation of human adipose-derived stem cells (hADSCs) using in vitro analyses. Methodology: CDNs were prepared using a membrane fragmentation approach, followed by drug loading. The CDN product, both drug-loaded and without drug, was analyzed based on size, shape, concentration of particles, concentration of proteins and DNA, drug loading, presence of membrane protein, biocompatibility in vitro, and ability to induce the differentiation of stem cells in vitro. Results: The synthesized drug-loaded CDNs had consistent size and shape, high drug loading efficiency, good cytocompatibility, and were internalized by hADSCs. They were able to induce the osteogenic differentiation of hADSCs in vitro, indicating their potential as an efficient drug delivery vehicle for bone regeneration. Significance: CDNs can be used to encapsulate and deliver several types of therapeutic molecules, co-deliver a combination of drugs, and be explored for targeted delivery. They can be incorporated into a suitable scaffold material for bone repair applications. |
