1,720,980 research outputs found
Development of a Small Animal Model of Non-union for the Evaluation of Xenogeneic Endothelial Progenitor Cell Therapy
Get PDFEndothelial progenitor cell (EPC) therapy has shown promise for the augmentation of bone healing in multiple preclinical studies; however the majority of work has used models of autologous cell transfer. A critical step in the translation of this therapy is the ability to test human EPCs in animal models, necessitating xenogeneic transfer. Accordingly, the aim of this work was to develop a small animal model of non-union suitable for the testing of xenogeneic EPCs. We hypothesized that the bone healing capacity of xenogeneic EPCs would be dependent upon the immune status of the recipient. Our results demonstrate that the bone healing effects of xenogeneic EPCs are proportional to the recipient’s level of immunodeficiency. Bone healing demonstrated a dose dependent relationship with recipient immune status, with only severely immunodeficient animals demonstrating reliable union. These findings suggest that a model with appropriately modulated immune response may be effective for testing human EPCs.M.Sc
The Effect of Bone Marrow-Derived Progenitor Cell Therapy to Improve Fracture Healing in a Diabetic Rat Critical Size Defect Model
Get PDFOur study aimed to explore the efficacy of locally implanted endothelial progenitor cells (EPCs) from healthy and diabetic animals on bone defect healing in healthy and diabetic recipients.
EPCs seeded on gelatin scaffolds were implanted in surgically created 5mm femoral defects to create six randomized treatment groups. The animals underwent biweekly radiographic assessment until the 10-week endpoint. Post-mortem specimens were analyzed by micro-computed tomography and biomechanics.
Most cell-treated healthy animals achieved union by 8 weeks. EPC-treated diabetic animals achieved higher radiographic scores than the diabetic controls. Healthy animals that received diabetic cells demonstrated greater bone volume, fractional bone volume, bone mineral density and biomechanical stiffness to diabetic animals that received diabetic cells but did not significantly differ from healthy animals that received healthy cells.
Thus, EPC therapy promotes fracture healing in diabetic animals irrespective of the cell source, though diabetes may decrease their healing capacities compared to treatment-matched healthy animals.M.Sc
The Impact of Psychosocial Factors on the Outcome of Surgical Repair for Rotator Cuff Tears – A Prospective Cohort (IMPROVE Study)
Get PDFRotator cuff tears are a common cause of pain and reduced function in the shoulder. The impact of psychosocial factors on patient outcomes following rotator cuff repair (RCR) surgery is unclear. The main goal of this thesis was to determine the association of psychosocial factors and outcomes in patients undergoing RCR surgery. Objectives: (1) To determine if psychosocial factors are associated with post-operative outcomes one-year after RCR surgery. (2) To determine if psychosocial factors are associated with disease severity at baseline. (3) To determine if psychosocial measures improve in patients one-year after RCR surgery. (4) To determine if treating surgeons are able to accurately assess patient’s mental health status at the baseline visit.
Methods: A multi-centre, prospective, cohort study was performed where patients with a full-thickness rotator cuff tear were enrolled prior to RCR surgery. Patients completed multiple validated questionnaires to measure psychosocial functioning (symptoms of depression, anxiety, pain catastrophizing, treatment expectations and social support) at the pre-operative visit. Patients were followed for one year after their surgery. The primary outcome was the patient-reported Western Ontario Rotator Cuff Index (WORC) completed at one-year. The secondary outcomes were the Constant Murley Score (Constant) and the EQ-5D-5L. A multivariable regression analysis was performed.
Results: 244 patients were enrolled, and 137 patients have completed a one-year follow-up. When controlling for other key variables, a multiple linear regression analysis did not demonstrate an independent association between any of the psychosocial factors and WORC scores at one year. Patients with higher levels of pain catastrophizing prior to surgery presented with worse WORC scores, Constant scores, and EQ-5D-5L health index scores at baseline and worse Constant scores at one-year. The remaining psychosocial factors were not associated with worse WORC scores at baseline. Scores on all of the psychosocial questionnaires improved between baseline and the one-year follow-up visit. The surgeons’ rating of patient’s mental health did not agree with the scores from the questionnaires.
Conclusion: In this patient population, we found a low rate of clinically significant psychological symptoms and when controlling for other variables, psychosocial factors did not have a significant impact on outcomes after RCR.Ph.D
The Effect of Bone Marrow-Derived Progenitor Cell Therapy to Improve Fracture Healing in a Diabetic Rat Critical Size Defect Model
No full textOur study aimed to explore the efficacy of locally implanted endothelial progenitor cells (EPCs) from healthy and diabetic animals on bone defect healing in healthy and diabetic recipients.
EPCs seeded on gelatin scaffolds were implanted in surgically created 5mm femoral defects to create six randomized treatment groups. The animals underwent biweekly radiographic assessment until the 10-week endpoint. Post-mortem specimens were analyzed by micro-computed tomography and biomechanics.
Most cell-treated healthy animals achieved union by 8 weeks. EPC-treated diabetic animals achieved higher radiographic scores than the diabetic controls. Healthy animals that received diabetic cells demonstrated greater bone volume, fractional bone volume, bone mineral density and biomechanical stiffness to diabetic animals that received diabetic cells but did not significantly differ from healthy animals that received healthy cells.
Thus, EPC therapy promotes fracture healing in diabetic animals irrespective of the cell source, though diabetes may decrease their healing capacities compared to treatment-matched healthy animals.M.Sc
The Induced Membrane Technique: Effects of Antibiotic-impregnated PMMA on Healing of a Rat Model of Segmental Defect
No full textThe induced membrane technique (IMT) is a therapeutic option for managing bone defects. Although not described in the original reports of the technique, surgeons now frequently incorporate antibiotics into the polymethylmethacrylate (PMMA) spacer to prevent or treat infection. However, the effects of these antibiotic concentrations on bone healing are not clear. The purpose of this study was to investigate if the practice of using antibiotic-impregnated spacers in the IMT, impacts bone repair. PMMA spacers with no antibiotics, low-dose and high-dose antibiotics were implanted in 5 mm segmental femoral defects. Bone grafting was performed four weeks later. Twelve weeks post-graft, defects treated with spacers without antibiotics and those treated with low-dose antibiotics had higher rates of radiographic union, and higher bone volume compared to defects treated with high-dose antibiotic spacers. In the context of the IMT, our results suggest that high doses of antibiotics in PMMA may negatively impact bone healing.M.Sc
Investigating Operative and Non-operative Treatments for Patella Fractures in Elderly, Low-demand Patients
Get PDFManagement protocols for displaced patella fractures in older (≥65 years) patients are lacking. While surgery is recommended for displaced fractures and non-operative management is suggested for non/minimally-displaced fractures in young/active patients, it is unclear if this algorithm is applicable to older, low-demand patients. The purpose of this thesis was to evaluate outcomes following operative and non-operative patella fracture management in older patients. Through an orthopaedic surgeon survey, we found that there remains a lack of consensus on the degree of displacement warranting operative management. Through a database study of 6258 patients, we found that re-operation rates are high, and emergency department readmissions are common but generally unrelated to patella fracture diagnosis. These results suggest that managing fractures in older patients is complex, and complications are prominent. Future studies comparing both interventions are needed. Protocols for a multicenter retrospective study and prospective randomised trial to address these questions are also presented.M.Sc
Characterizing the Effects of Endothelial Progenitor Cells and Local Antibiotics on Bone Healing and Infection in a Small Animal Model
Get PDFThe treatment of infected nonunions remains a major clinical challenge for orthopedic surgeons, often requiring multiple, complex surgeries to effectively cure. This condition, and the multiple surgeries required to treat it, are debilitating to patients and present a significant burden on the healthcare system, necessitating a strong need for the development of more effective treatments. Endothelial progenitor cells (EPCs) and local antibiotics are effective in promoting fracture healing and reducing infection, respectively. However, their combined use in the treatment of infected nonunions has not yet been explored. This study aimed to investigate the hypothesis that EPCs and local antibiotics could be used to effectively treat infected nonunions in a single-stage treatment. First, we created non-contaminated and contaminated 1 mm fracture defect models in order to determine the impact of local vancomycin on bone healing and its ability to eradicate infection in the setting of contamination. Additionally, we investigated the combination of EPCs with local antibiotics (vancomycin and rifampin) in non-contaminated and contaminated fracture models with critical sized (5 mm) bone defects. This study aimed to assess the bone-healing capacity of EPCs in the presence of local antibiotics and their combined efficacy in the treatment of nonunion and infection. Bone healing progression was monitored using radiography, micro-CT, and biomechanics, while infection status was assessed through radiography and microbiology on tissue specimens collected after harvest at 10 weeks. Our results showed that local vancomycin did not have a negative impact on bone healing and was effective as a prophylaxis against infection in the setting of contamination. Furthermore, we found that the combination of EPCs with local antibiotics was highly effective in promoting bone healing and eliminating infection in our animal model of infected nonunion. These findings support the use of local antibiotics in the management of at-risk and contaminated fractures, as well as the use of EPCs with local antibiotics for treating infected nonunions. Implementing an effective single-stage surgical treatment for infected nonunions will result in a reduction in the number of procedures, faster recovery times, and reduced associated costs, thus improving the overall treatment outcomes.Ph.D.2025-11-13 00:00:0
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The Effects of Endothelial Progenitor Cell Therapy on Fracture Healing and Infection Status Outcomes in a Low-grade Infected Rat Critical-size Defect Model
Get PDFLow-grade infection represents a common cause of nonunion and complicates its management. Endothelial progenitor cells (EPCs) are capable of healing bone defects, but their potential antimicrobial properties remain unknown. We aimed to evaluate EPCs’ bone healing and infection treatment potential in an infected nonunion setting, with and without local antibiotics. In our first three experiments, we established a consistent low-grade infected nonunion model, selected an effective local antibiotic therapy, encountered EPC functionality issues while investigating bone healing outcomes, and troubleshooted to reproduce high bone healing rates. Our final experiment analyzed infection outcomes and did not demonstrate any significant effect of EPCs on low-grade infection eradication in the presence or absence of local antibiotics. However, the final study was small-scale and lacked sufficient statistical power to demonstrate an effect. Therefore, further experimentation with larger-scale study designs are necessary to more adequately investigate the combination of EPCs and local antibiotics as a potential single-stage therapy for low-grade infected nonunions.M.Sc
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