Publications by authors named "Kirk McGilvray"

Article Synopsis
  • The high failure rate of surgical repairs for tendinopathies has led researchers to explore adjunct therapies, specifically exosomes (EVs) from mesenchymal stromal cells (MSCs) which have shown promise in animal studies for enhancing tendon healing.
  • Research indicates that exosomes from tendon-specific cells (tenocytes) may be more effective than MSC-derived exosomes in promoting tendon healing due to their distinct functional properties.
  • The study found that tenocyte-derived exosomes (TdEVs) altered macrophage responses in ways that support tendon healing, while MSC-derived exosomes triggered different pathways related to inflammation and oxidative stress, highlighting the importance of the source of EVs in tendon repair processes.
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Objectives: This study explored the efficacy of collecting temporal fracture site compliance data via an advanced direct electromagnetic coupling (DEC) system equipped with a Vivaldi-type antenna, novel calibration technique, and multi-antenna setup (termed maDEC) as an approach to monitor acute fracture healing progress in a translational large animal model. The overarching goal of this approach was to provide insights into the acute healing dynamics, offering a promising avenue for optimizing fracture management strategies.

Methods: A sample of twelve sheep, subjected to ostectomies and intramedullary nail fixations, was divided into two groups, simulating normal and impaired healing scenarios.

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Several tendon and ligament animal models were presented at the 2022 Orthopaedic Research Society Tendon Section Conference held at the University of Pennsylvania, May 5 to 7, 2022. A key objective of the breakout sessions at this meeting was to develop guidelines for the field, including for preclinical tendon and ligament animal models. This review summarizes the perspectives of experts for eight surgical small and large animal models of rotator cuff tear, flexor tendon transection, anterior cruciate ligament tear, and Achilles tendon injury using the framework: "Why, Who, What, Where, When, and How" (5W1H).

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Tendon injuries and disease are resistant to surgical repair; thus, adjunct therapies are widely investigated, especially mesenchymal stromal cells (MSCs) and, more recently, their extracellular vesicles (MSCdEVs), for example, exosomes. Thought to act on resident and infiltrating immune cells, the role of MSCdEVs in paracrine signaling is of great interest. This study investigated how MSCdEVs differ from analogs derived from resident (tenocyte) populations (TdEV).

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The high failure rate of rotator cuff repair surgeries is positively correlated with age, yet the biomechanical changes to the tendons of the rotator cuff with age have not been described. As such, we sought to benchmark and characterize the biomechanical and histopathological properties with the accompanying gene expression of human rotator cuff tendons as a function of age and histopathological degeneration. All four rotator cuff tendons from fresh human cadaver shoulders underwent biomechanical, histopathological, and gene expression analyses.

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Background: Osteoporosis is an independent risk factor for failure after arthroscopic rotator cuff repair. Since rerupture rates after rotator cuff repair are associated with decreased bone mineral density and bone microarchitecture, adaptations of biomechanical properties of the rotator cuff enthesis in patients with osteoporosis remain unclear. Additionally, the effects of osteogenic therapy carrier drugs used for the treatment of osteoporosis on rotator cuff structure and properties have not been previously documented.

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Background: Rapid prediction of adverse bone fracture healing outcome (e.g., nonunion and/or delayed union) is essential to advise adjunct therapies to reduce patient suffering and improving healing outcome.

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The implementation of novel coaxial dipole antennas has been shown to be a satisfactory diagnostic platform for the prediction of orthopaedic bone fracture healing outcomes. These techniques require mechanical deflection of implanted metallic hardware (i.e.

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Cardiac biomechanics play a significant role in the progression of structural heart diseases (SHDs). SHDs alter baseline myocardial biomechanics leading to single or bi-ventricular dysfunction. But therapies for left ventricle (LV) failure patients do not always work well for right ventricle (RV) failure patients.

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A tibial tuberosity advancement (TTA), used to treat lameness in the canine stifle, provides a framework to investigate implant performance within an uneven loading environment due to the dominating patellar tendon. The purpose of this study was to reassess how we design orthopaedic implants in a load-bearing model to investigate potential for improved osseointegration capacity of fully-scaffolded mechanically-matched additive manufactured (AM) implants. While the mechanobiological nature of bone is well known, we have identified a lower limit in the literature where investigation into exceedingly soft scaffolds relative to trabecular bone ceases due to the trade-off in mechanical strength.

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Objective: Shoulder pain is commonly attributed to rotator cuff injury or osteoarthritis. Ovine translational models are used to investigate novel treatments aimed at remedying these conditions to prevent articular cartilage degeneration and subsequent joint degradation. However, topographical properties of articular cartilage in the ovine shoulder are undefined.

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Trauma to the soft tissues of the ankle joint distal syndesmosis often leads to syndesmotic instability, resulting in undesired movement of the talus, abnormal pressure distributions, and ultimately arthritis if deterioration progresses without treatment. Historically, syndesmotic injuries have been repaired by placing a screw across the distal syndesmosis to provide rigid fixation to facilitate ligament repair. While rigid syndesmotic screw fixation immobilizes the ligamentous injury between the tibia and fibula to promote healing, the same screws inhibit normal physiologic movement and dorsiflexion.

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Background: Chronic degeneration of rotator cuff tendons is a major contributing factor to the unacceptably high prevalence of rotator cuff repair surgery failures. The etiology of chronic rotator cuff degeneration is not well understood, and current therapies are not effective, necessitating preclinical research to fill this knowledge gap. Unfortunately, current large animal models rely on enthesis disruption as a means of model generation, which is not representative of human patients with chronic rotator cuff degeneration prior to full-thickness tears.

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Background Context: While the clinical effectiveness of recombinant human Platelet Derived Growth Factor-B chain homodimer combined with collagen and β-tricalcium phosphate (rhPDGF-BB + collagen/β-TCP) treatment for indications involving hindfoot and ankle is well-established, it is not approved for use in spinal interbody fusion, and the use of autograft remains the gold standard.

Purpose: The purpose of this study was to compare the effects of rhPDGF-BB + collagen/β-TCP treatment on lumbar spine interbody fusion in an ovine model to those of autograft bone and collagen/β-TCP treatments using biomechanical, radiographic, and histological assessment techniques.

Study Design: Thirty-two skeletally mature Columbian Rambouillet sheep were used to evaluate the safety and effectiveness of rhPDGF-BB + collagen/β-TCP matrix in a lumbar spinal fusion model.

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A novel canine tibial plateau leveling osteotomy (TPLO) fixation device was recently developed with design features such as titanium alloy (TA) material, distal monocortical screw fixation, and a point contact undersurface specifically targeted to reduce surgical site infection rates by ensuring tissue perfusion under the plate. The strength of the novel TPLO construct was compared with that of a predicate stainless steel (SS) locking plate construct with bicortical screws in 16 paired cadaveric canine limbs. The mean loads to failure were 716.

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Background: Expedient prediction of adverse bone fracture healing (delayed- or non-union) is necessary to advise secondary treatments for improving healing outcome to minimize patient suffering. Radiographic imaging, the current standard diagnostic, remains largely ineffective at predicting nonunions during the early stages of fracture healing resulting in mean nonunion diagnosis times exceeding six months. Thus, there remains a clinical deficit necessitating improved diagnostic techniques.

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Background: The purpose of this study was to evaluate the mechanical, structural, and histologic quality of rotator cuff repairs augmented with an interposition electrospun nanofiber scaffold composed of polyglycolic acid (PGA) and poly-L-lactide-co-ε-caprolactone (PLCL) in an acute sheep model.

Methods: Forty acute infraspinatus tendon detachment and repair procedures were performed in a sheep infraspinatus model using a double-row transosseous-equivalent anchor technique either with an interposition nanofiber scaffold composed of polyglycolic acid-poly-L-lactide-co-ε-caprolactone or with no scaffold. Animals were euthanized at the 6-week (20 samples) and 12-week (20 samples) postoperative time points to assess the biomechanical and histologic properties of the repairs and to compare differences within each group.

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Background: Untreated rotator cuff tears lead to irreversible tendon degeneration, resulting in unacceptable repair prognosis. The inability of current animal models of degenerated rotator cuff tendons to more fully emulate the manifestation and degree of pathology seen in humans with a previously torn rotator cuff tendon (s) significantly impairs the development of novel therapeutics. Therefore, the objective of this study was to develop a large-animal translational model of enthesis damage to the rotator cuff tendons to mimic the chronic degenerative changes that occur in patients that demonstrate clinical manifestations of tendinopathy.

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Background: The range of diagnostic modalities available to evaluate superficial digital flexor tendon (SDFT) injury includes magnetic resonance imaging (MRI), computed tomography (CT) and ultrasonography (US). Direct, comprehensive comparison of multi-modality imaging characteristics to end-point data has not previously been performed using a model of tendinopathy but is required to obtain a better understanding of each modality's diagnostic capabilities.

Objective: To compare CT, MRI and US evaluation to outcome measures for histologic, biochemical and biomechanical parameters using an equine surgical model of tendinopathy.

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bioreactors are a promising approach for engineering vascularized autologous bone grafts to repair large bone defects. In this pilot parametric study, we first developed a three-dimensional (3D) printed scaffold uniquely designed to accommodate inclusion of a vascular bundle and facilitate growth factor delivery for accelerated vascular invasion and ectopic bone formation. Second, we established a new sheep deep circumflex iliac artery (DCIA) model as an bioreactor for engineering a vascularized bone graft and evaluated the effect of implantation duration on ectopic bone formation.

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Autologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. Recombinant human bone morphogenetic protein 2 (rhBMP-2) can stimulate bone regeneration and enhance the healing efficacy of bone grafts. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest.

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The knee is the most common site for translational cartilage research in sheep, though topographic features of articular cartilage across surfaces are unspecified. We aimed to characterize the mechanical, morphological, and biochemical properties of articular cartilage across ovine knee surfaces and document variations between and within surface locations. Regions of interest (ROIs) were delineated across surfaces of 10 healthy ovine knees.

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Objective: To determine the biomechanical properties of pedicle screw external fixation (PDW) for equine mandibular fracture repair and compare PDW to locking compression plates (LCP).

Study Design: Cadaveric study.

Sample Population: Sixteen adult equine mandibles.

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Objective:  Rotator cuff tendon tears are the most common soft tissue injuries in the shoulder joint. Various animal models have been described for this condition, but all current translational animal models have inherent weaknesses in their ability to generate chronically degenerated rotator cuff tendons. The objective of this study was to evaluate a partial infraspinatus tendon transection model as a means of creating a chronically degenerated rotator cuff tendon in an ovine model and compare the injury characteristics of this model to those observed in human patients with severe chronic rotator cuff tendon injuries.

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Objective:  Screw loosening in fracture fixation poses a clinical risk which may lead to implant failure, particularly in poor bone quality. The objective of this study was to examine the effectiveness of a novel screw retention technology (SRT) for increased screw purchase in a large animal metatarsal fracture model.

Study Design:  This was a biomechanical, radiographic, and histological study utilizing an ovine metatarsal fracture model.

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