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  • 1
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2017
    In:  International Orthopaedics Vol. 41, No. 11 ( 2017-11), p. 2337-2343
    In: International Orthopaedics, Springer Science and Business Media LLC, Vol. 41, No. 11 ( 2017-11), p. 2337-2343
    Type of Medium: Online Resource
    ISSN: 0341-2695 , 1432-5195
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 1459230-7
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  • 2
    In: Injury, Elsevier BV, Vol. 53, No. 6 ( 2022-06), p. 1848-1853
    Type of Medium: Online Resource
    ISSN: 0020-1383
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2011808-9
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  • 3
    In: Journal of Orthopaedic Research, Wiley
    Abstract: Nonunion and segmental bone defects are complex issues in orthopedic trauma. The use of endothelial progenitor cells (EPCs), as part of a cell‐based therapy for bone healing is a promising approach. In preclinical studies, culture medium (CM) is commonly used to deliver EPCs to the defect site, which has the potential for immunogenicity in humans. The goal of this study was to find an effective and clinically translatable delivery medium for EPCs. Accordingly, this study compared EPCs delivered in CM, phosphate‐buffered saline (PBS), platelet‐poor plasma (PPP), and platelet‐rich plasma (PRP) in a rat model of femoral critical‐size defects. Fischer 344 rats ( n  = 35) were divided into six groups: EPC+CM, EPC+PBS, EPC+PPP, EPC+PRP, PPP alone, and PRP alone. A 5 mm mid‐diaphyseal defect was created in the right femur and stabilized with a miniplate. The defect was filled with a gelatin scaffold impregnated with the corresponding treatment. Radiographic, microcomputed tomography and biomechanical analyses were performed. Overall, regardless of the delivery medium, groups that received EPCs had higher radiographic scores and union rates, higher bone volume, and superior biomechanical properties compared to groups treated with PPP or PRP alone. There were no significant differences in any outcomes between EPC subgroups or between PPP and PRP alone. These results suggest that EPCs are effective in treating segmental defects in a rat model of critical‐size defects regardless of the delivery medium used. Consequently, PBS could be the optimal medium for delivering EPCs, given its low cost, ease of preparation, accessibility, noninvasiveness, and nonimmunogenic properties.
    Type of Medium: Online Resource
    ISSN: 0736-0266 , 1554-527X
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2050452-4
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  • 4
    In: Journal of Tissue Engineering and Regenerative Medicine, Hindawi Limited, Vol. 2023 ( 2023-3-9), p. 1-9
    Abstract: Endothelial progenitor cell (EPC) therapy has been successfully used in orthopaedic preclinical models to heal bone defects. However, no previous studies have investigated the dose-response relationship between EPC therapy and bone healing. This study aimed to assess the effect of different EPC doses on bone healing in a rat model to define an optimal dose. Five-millimeter segmental defects were created in the right femora of Fischer 344 rats, followed by stabilization with a miniplate and screws. Rats were assigned to one of six groups (control, 0.1 M, 0.5 M, 1.0 M, 2.0 M, and 4.0 M; n = 6), receiving 0, 1 × 105, 5 × 105, 1 × 106, 2 × 106, and 4 × 106 EPCs, respectively, delivered into the defect on a gelatin scaffold. Radiographs were taken every two weeks until the animals were euthanized 10 weeks after surgery. The operated femora were then evaluated using micro-computed tomography and biomechanical testing. Overall, the groups that received higher doses of EPCs (0.5 M, 1.0 M, 2.0 M, and 4.0 M) reached better outcomes. At 10 weeks, full radiographic union was observed in 67% of animals in the 0.5 M group, 83% of animals in the 1.0 M group, and 100% of the animals in the 2.0 M and 4.0 M groups, but none in the control and 0.1 M groups. The 2.0 M group also displayed the strongest biomechanical properties, which significantly improved relative to the control and 0.1 M groups. In summary, this study defined a dose-response relationship between EPC therapy and bone healing, with 2 × 106 EPCs being the optimal dose in this model. Our findings emphasize the importance of dosing considerations in the application of cell therapies aimed at tissue regeneration and will help guide future investigations and clinical translation of EPC therapy.
    Type of Medium: Online Resource
    ISSN: 1932-7005
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2023
    detail.hit.zdb_id: 2316155-3
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  • 5
    In: Journal of Bone and Joint Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 21 ( 2018-11-7), p. 1871-1878
    Abstract: The Radiographic Union Score for Tibial fractures (RUST) and the modified version of the system, mRUST, are popular standards for assessing fracture-healing progress with use of radiographs. To our knowledge, this is the first study to experimentally validate the ability of RUST and mRUST to accurately assess bone-healing progression with use of both micro-computed tomography (micro-CT) scanning and biomechanical testing. Methods: Adult male rats (n = 29) underwent osteotomy with a midshaft fracture gap repaired with use of a polyetheretherketone plate. Anteroposterior and lateral radiographs were made of the repaired femora prior to rat death at end points of 5, 6, 7, 8, 9, and 17 weeks, and 2 fellowship-trained orthopaedic trauma surgeons independently assigned RUST and mRUST scores to repaired femora. The repaired and intact contralateral femora were then dissected. Bones underwent dissection, micro-CT scanning, and biomechanical torsion testing at the end points. Results: RUST scores ranged from 5 to 12 and mRUST scores ranged from 5 to 16. Intraclass correlation coefficients (ICCs) were 0.89 (95% confidence interval [CI]: 0.78 to 0.94) for RUST and 0.86 (95% CI: 0.74 to 0.93) for mRUST, which fall within the “almost perfect agreement” category for ICCs. Spearman rank correlation coefficients (R S ) showed correlation of RUST (R S range, 0.456 to 0.818) and mRUST (R S range, 0.519 to 0.862) with micro-CT measurements of mineralized callus volume (BV), total callus volume (TV), and BV/TV ratio, but less so with bone mineral density (BMD). Additionally, RUST (R S range, 0.524 to 0.863) and mRUST (R S range, 0.434 to 0.850) were correlated with some biomechanical properties. A RUST score of 10 or an mRUST score of 15 may be considered the threshold above which a plated bone is “healed” because, at these scores, 120% or 140% of failure torque, respectively, was achieved by the repaired femora as compared with the intact contralateral femora. Conclusions: RUST and mRUST both show strong statistical correlations with micro-CT and biomechanical parameters. Clinical Relevance: RUST and mRUST scoring systems provide clinicians with validated, reliable, and available tools to assess the progress of fracture-healing.
    Type of Medium: Online Resource
    ISSN: 0021-9355 , 1535-1386
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
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  • 6
    In: Stem Cells International, Hindawi Limited, Vol. 2017 ( 2017), p. 1-10
    Abstract: The repair of segmental bone defects remains a significant challenge for orthopaedic surgeons. Endothelial progenitor cells (EPCs) have successfully promoted the repair of acute defects in animal models; however, the ability of EPCs to induce the repair of chronic nonhealing defects, such as those often encountered clinically, has not been investigated. Therefore, the purpose of this study was to investigate the ability of EPCs delivered in delayed fashion to induce the repair of nonhealing defects in a clinically relevant model. In order to simulate delayed treatment, 5 mm segmental defects in Fischer 344 rat femora were treated with bone marrow-derived EPCs on a Gelfoam scaffold at 3 weeks post creation of the defect. At ten weeks posttreatment, 100% of EPC-treated defects achieved union, whereas complete union was only achieved in 37.5% of defects treated with Gelfoam alone. Furthermore, significant increases in ultimate torque ( p = 0.022 ) and torsional stiffness ( p = 0.003 ) were found in EPC-treated defects compared to controls. Critically, no differences in outcomes were observed between acute and delayed EPC treatments. These results suggest that EPCs can enhance bone healing when applied in an acute or delayed fashion and that their use may represent a clinically translatable therapy for bone healing in humans.
    Type of Medium: Online Resource
    ISSN: 1687-966X , 1687-9678
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2017
    detail.hit.zdb_id: 2573856-2
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  • 7
    Online Resource
    Online Resource
    Wiley ; 2021
    In:  Journal of Orthopaedic Research Vol. 39, No. 7 ( 2021-07), p. 1359-1367
    In: Journal of Orthopaedic Research, Wiley, Vol. 39, No. 7 ( 2021-07), p. 1359-1367
    Abstract: Fracture healing is a complex process requiring mechanical stability, an osteoconductive matrix, and osteoinductive and osteogenic biology. This intricate process is easily disrupted by various patient factors such as chronic disease and lifestyle. As the medical complexity and age of patients with fractures continue to increase, the importance of developing relevant experimental models is becoming paramount in preclinical research. The objective of this review is to describe the most common small animal models of systemically impaired fracture healing used in the orthopedic literature including osteoporosis, diabetes mellitus, smoking, alcohol use, obesity, and ageing. This review will provide orthopedic researchers with a summary of current models of systemically impaired fracture healing used in small animals and present an overview of the methods of induction for each condition.
    Type of Medium: Online Resource
    ISSN: 0736-0266 , 1554-527X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2050452-4
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  • 8
    In: Injury, Elsevier BV, Vol. 49, No. 2 ( 2018-02), p. 177-183
    Type of Medium: Online Resource
    ISSN: 0020-1383
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2011808-9
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  • 9
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  OTA International: The Open Access Journal of Orthopaedic Trauma Vol. 5, No. 1S ( 2022-03-10), p. e176-
    In: OTA International: The Open Access Journal of Orthopaedic Trauma, Ovid Technologies (Wolters Kluwer Health), Vol. 5, No. 1S ( 2022-03-10), p. e176-
    Type of Medium: Online Resource
    ISSN: 2574-2167
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 3019952-9
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  • 10
    Online Resource
    Online Resource
    British Editorial Society of Bone & Joint Surgery ; 2020
    In:  The Bone & Joint Journal Vol. 102-B, No. 12 ( 2020-12-01), p. 1723-1734
    In: The Bone & Joint Journal, British Editorial Society of Bone & Joint Surgery, Vol. 102-B, No. 12 ( 2020-12-01), p. 1723-1734
    Abstract: The purpose of this study was to: review the efficacy of the induced membrane technique (IMT), also known as the Masquelet technique; and investigate the relationship between patient factors and technique variations on the outcomes of the IMT. Methods A systematic search was performed in CINAHL, The Cochrane Library, Embase, Ovid MEDLINE, and PubMed. We included articles from 1 January 1980 to 30 September 2019. Studies with a minimum sample size of five cases, where the IMT was performed primarily in adult patients (≥ 18 years old), in a long bone were included. Multivariate regression models were performed on patient-level data to determine variables associated with nonunion, postoperative infection, and the need for additional procedures. Results A total of 48 studies were included, with 1,386 cases treated with the IMT. Patients had a mean age of 40.7 years (4 to 88), and the mean defect size was 5.9 cm (0.5 to 26). In total, 82.3% of cases achieved union after the index second stage procedure. The mean time to union was 6.6 months (1.4 to 58.7) after the second stage. Our multivariate analysis of 450 individual patients showed that the odds of developing a nonunion were significantly increased in those with preoperative infection. Patients with tibial defects, and those with larger defects, were at significantly higher odds of developing a postoperative infection. Our analysis also demonstrated a trend towards the inclusion of antibiotics in the cement spacer having a protective effect against the need for additional procedures. Conclusion The IMT is an effective management strategy for complex segmental bone defects. Standardized reporting of individual patient data or larger prospective trials is required to determine the optimal implementation of this technique. This is the most comprehensive review of the IMT, and the first to compile individual patient data and use regression models to determine predictors of outcomes. Cite this article: Bone Joint J 2020;102-B(12):1723–1734.
    Type of Medium: Online Resource
    ISSN: 2049-4394 , 2049-4408
    Language: English
    Publisher: British Editorial Society of Bone & Joint Surgery
    Publication Date: 2020
    detail.hit.zdb_id: 2697480-0
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