Search

Atypical femoral fractures (AFFs) are rare fractures usually associated with medications that can ultimately alter bone metabolism. Imatinib, a drug prescribed for treatment of chronic myeloid leukemia (CML), has been associated with altered bone homeostasis, however, with unknown clinical significance. Here, we present the case of a 17‐year‐old female, with a diagnosis of CML undergoing chronic imatinib therapy, who developed an AFF treated successfully with prophylactic fixation with intramedullary nailing. Our case underscores the importance of prompt recognition of this entity to allow patients timely appropriate care, even at an early age. [ABSTRACT FROM AUTHOR]

Background: Up to 80% of patients in the United States report dissatisfaction with pain management following orthopaedic surgery. Inadequate pain management is linked to negative outcomes, including increased costs, readmission rates, and chronic pain risk. Traditional pain management protocols often emphasise the biological components of pain, overlooking psychological and social. This systematic review addresses this gap by answering two key questions: (1) What factors are associated with increased risk of unsatisfactory pain management following orthopaedic surgery? (2) What are the key components of successful pain management protocols following orthopaedic surgery? Methods: PRISMA guidelines were followed with a search of relevant online databases. Studies were included if they were in English, provided patient feedback/satisfaction with pain management (quantitative studies) or provided satisfaction with pain management or healthcare team feedback (qualitative studies) or explored patient variables associated with satisfaction with pain management. Results: Of the 845 articles screened, 27 met the inclusion criteria. Synthesis suggested that while perceived severity and duration of pain are often assumed to be the primary drivers of patient satisfaction related to pain management, patients with a sense of control over their pain reported higher satisfaction, regardless of actual pain level. History of opioid misuse, patient expectations, and patient mental health were associated with dissatisfaction. Conclusion: Pre‐operative education and ongoing communication, particularly regarding patient risk‐factors and multi‐modal pain management strategies, appear to enhance patients' sense of control and satisfaction. Future research should explore whether individualised pre‐operative education can improve satisfaction with post‐surgical orthopaedic pain management. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries are common injuries that often have a drastic effect on patient's activities of daily living and physical function. While techniques for the surgical repair of these injuries have improved over time, rehabilitation methods following these repairs have been non‐standardized and under researched. Electronic searches were conducted in Ovid/Medline and SCOPUS to identify articles that discuss rehabilitation and exercise following peripheral nerve injury in animal models and its effects on peripheral nerve regeneration and recovery of function. Thirty‐eight articles met inclusion criteria; all were prospective studies in animal models. This systematic review suggests that exercise is a useful tool in returning autonomy to the individual and has beneficial effects in the recovery from peripheral nerve injury. It is beneficial to use rehabilitation exercises following the repair of peripheral nerve injuries to promote regeneration, and timing of that exercise may be just as important as the exercise prescribed. However, further studies with standardized models and outcome measures need to be conducted before translation to clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: While the importance of patient adherence to treatment protocols is firmly accepted, a definition for adherence and mechanisms to address non‐adherence are not well established. The goals of this study were to define adherence and identify barriers and enablers for adherence partnerships through the lens of the orthopaedic healthcare team. Methods: The qualitative study was designed using concepts from grounded theory. Eight focus groups, comprised of orthopaedic healthcare team members, were conducted to identify factors influencing orthopaedic patient adherence to treatment plans. Results: Healthcare team members identified a range of factors affecting patient adherence. Participants conveyed that patient non‐adherence can be a deliberate decision but can also result from barriers faced by the patient. Synthesis of themes identified distinct phases of adherence and culminated in the creation of a preliminary model that encapsulates healthcare team and patient factors impacting adherence, which was entitled, The Barriers and Enablers to Treatment Adherence (BETA) Model. Conclusion: The study findings alleviate the patient from the sole burden of adherence, recognising the influences that the healthcare team and system have on patients' ability to adhere. The BETA model of patient adherence represents the first step to mitigating non‐adherence by providing a foundation for programmatic research aimed at developing and evaluating interventions and management strategies that empower healthcare teams to effectively equip patients for adherence, leading to optimised patient outcomes following orthopaedic interventions. [ABSTRACT FROM AUTHOR]

Posttraumatic osteoarthritis (PTOA) significantly affects patients with pilon fractures even after adequate anatomical reduction, and treatment strategies targeting the biologic mediators of PTOA are needed. This study was designed to determine the effects of intra‐articular injection of platelet‐rich plasma (PRP) on synovial fluid (SF) biomarkers for patients undergoing open reduction and internal fixation (ORIF) of pilon fractures. Patients undergoing staged management of pilon fractures were enrolled in a prospective, double‐blinded, randomized, and placebo‐controlled clinical trial to determine the effects of a single intra‐articular injection of leukocyte‐reduced PRP on SF biomarkers. Arthrocentesis of the injured and uninjured ankles was performed at the time of external skeletal fixation (ESF) and ORIF. Patients were randomized to receive either autogenous leukocyte‐reduced PRP or saline (control) via intra‐articular injection into the injured ankle at the time of ESF. SF biomarker concentrations were compared—uninjured, injured pretreatment, and saline‐injected or PRP‐injected. Eleven patients (PRP, n = 5; saline, n = 6) completed the study. Twenty‐one uninjured, and 11 injured pretreatment, five PRP‐treated, and six saline‐treated SF samples were analyzed. PRP‐treated SF contained significantly higher levels of PDGF‐AA (p = 0.046) and significantly lower levels of MMP‐3 (p = 0.042), MMP‐9 (p = 0.009), IL‐1β (p = 0.049), IL‐6 (p < 0.01), IL‐8 (p = 0.048), and PGE2 (p < 0.04). This study provided mechanistic data to suggest that a single intraarticular injection of leukocyte‐reduced PRP is associated with anti‐inflammatory, anti‐degradative, and anabolic responses compared with saline control. These findings provide the impetus for investigating long‐term clinical outcomes after PRP injection as an orthobiologic adjunct to ORIF for mitigating the incidence and severity of PTOA after pilon fractures. [ABSTRACT FROM AUTHOR]

Many factors contribute to the development and progression of intervertebral disc (IVD) degeneration. This study was designed to assess the effects of compressive load magnitude on IVD metabolism. It was hypothesized that as load magnitude increased, there would be a significant increase in release of proinflammatory and degradative biomarkers, and a significant decrease in tissue proteoglycan (GAG) and collagen contents compared with unloaded controls. IVD whole organ functional spinal units (FSU) consisting of cranial and caudal body halves, cartilage endplates, and IVD (n = 36) were harvested from the tails of six Sprague Dawley rats, and FSUs were cultured at 0.0 MPa, 0.5 MPa, or 1.0 MPa at 0.5 Hz for 3 days. After culture, media were collected for biomarker analysis and FSUs were analyzed for extracellular matrix composition. Significant differences were determined using a one‐way analysis of variance or Kruskal–Wallis test and post hoc analyses. Media concentrations of IFN‐γ, IL‐6, IL‐1β, and MMP‐8 were significantly higher in the 0.5 MPa compared with the 0.0 MPa group. Media concentrations of PGE2 and TIMP‐1 were significantly higher in the 1.0 MPa group compared with the 0.0 MPa group, and media PGE2 was significantly higher in the 1.0 MPa group compared with the 0.5 MPa group. Media GAG content was significantly higher in the 1.0 MPa group compared with the 0.0 MPa group, and percent GAG in the tissue was significantly lower in 0.5 MPa and 1.0 MPa groups compared with the 0.0 MPa group. Clinical Significance: These data suggest that there are magnitude‐dependent inflammatory and degradative IVD responses to cyclic loading, which may contribute to IVD degeneration. [ABSTRACT FROM AUTHOR]

Preclinical studies involving large animal models aim to recapitulate the clinical situation as much as possible and bridge the gap from benchtop to bedside. To date, studies investigating intervertebral disc (IVD) degeneration and regeneration in large animal models have utilized a wide spectrum of methodologies for outcome evaluation. This paper aims to consolidate available knowledge, expertise, and experience in large animal preclinical models of IVD degeneration to create a comprehensive tool box of anatomical and functional outcomes. Herein, we present a Large Animal IVD Scoring Algorithm based on three scales: macroscopic (gross morphology, imaging, and biomechanics), microscopic (histological, biochemical, and biomolecular analyses), and clinical (neurologic state, mobility, and pain). The proposed algorithm encompasses a stepwise evaluation on all three scales, including spinal pain assessment, and relevant structural and functional components of IVD health and disease. This comprehensive tool box was designed for four commonly used preclinical large animal models (dog, pig, goat, and sheep) in order to facilitate standardization and applicability. Furthermore, it is intended to facilitate comparison across studies while discerning relevant differences between species within the context of outcomes with the goal to enhance veterinary clinical relevance as well. Current major challenges in pre‐clinical large animal models for IVD regeneration are highlighted and insights into future directions that may improve the understanding of the underlying pathologies are discussed. As such, the IVD research community can deepen its exploration of the molecular, cellular, structural, and biomechanical changes that occur with IVD degeneration and regeneration, paving the path for clinically relevant therapeutic strategies. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a complex disease with biologic, biomechanical, and clinical heterogeneity among patients. Relationships among OA tissue metabolism, histopathology, and extracellular matrix (ECM) composition have not been well characterized. It was hypothesized that moderate (r =.4‐.69) to strong (r >.7) correlations exist among these different measures of disease severity in osteochondral tissues from OA knees. Joint surfaces were obtained from patients (n = 6) undergoing total knee arthroplasty. Osteochondral explants (n = 136) were created and cultured for 3 days. Culture media were collected for biomarker analyses, and tissue was assessed for viability, histological scoring, and ECM composition. Correlations among media biomarker concentrations, histological scoring, ECM composition, and viability were determined using a Spearman correlation. GRO‐α, IL‐6, IL‐8, and MCP‐1 showed strong positive correlations to each other, and moderate positive correlations to NO, PGE2, and MMP‐2. Total MMP activity, MMP‐9, and MMP‐13 had strong positive correlations to each other, and moderate positive correlations to MMP‐1. MMP‐2 had a moderate to strong positive correlations to histological scores (total and cartilage structure) and collagen content. MMP‐2, IL‐6, IL‐8, and MCP‐1 had moderate negative correlations, and MMP‐9 had a moderate positive correlation, to viability. GRO‐α, IL‐6, IL‐8, and MCP‐1 had moderate positive correlations to collagen content. MMP‐9, MMP‐13, and total MMP activity had moderate negative correlations to tissue GAG. The data suggest links among proinflammatory and degradative pathways are present in OA osteochondral tissues. Further characterization of these links have the potential to delineate mechanisms of disease and diagnostic and therapeutic targets for knee OA. [ABSTRACT FROM AUTHOR]

Osteochondral allograft (OCA) transplantation can restore large articular defects in the knee. Bipolar OCA transplantations for partial and whole joint resurfacing often have less favorable results than single‐surface transplants. This study was designed to use a large animal model to test the hypothesis that unicompartmental bipolar osteochondral and meniscal allograft transplantation (BioJoint) would be as or more effective for treatment of medial compartment osteoarthritis (OA) compared to standard‐of‐care nonoperative treatment. OA was induced in one knee of each research hound (n = 8) using a meniscal release model and pretreatment assessments were performed. After 3 months, dogs were randomly assigned to either the control group (n = 4, no surgical intervention, daily nonsteroidal antiinflammatory drugs [NSAIDs]) or the BioJoint group (n = 4). Clinical, radiographic, and arthroscopic assessments were performed longitudinally and histopathology was evaluated at the 6‐month endpoint. At study endpoint, functional, pain, and total pressure index measures, as well as radiographic and arthroscopic grading of graft appearance and joint health, demonstrated superior outcomes for BioJoints compared to NSAID controls. Furthermore, histologic assessments showed that osteochondral and meniscal transplants maintain integrity and integrated into host tissues. Clinical significance: The results support the safety and efficacy of unicompartmental bipolar osteochondral and meniscal allograft transplantation in a preclinical model with highly functional outcomes without early OA progression. [ABSTRACT FROM AUTHOR]

Meniscal allograft transplantation (MAT) can be a safe, effective treatment for meniscal deficiency resulting in knee dysfunction, leading to osteoarthritis (OA) without proper treatment with 5‐year functional success rates (75%‐90%). While different grafts and techniques have generally proven safe and effective, complications include shrinkage, extrusion, progression of joint pathology, and failure. The objective of this study was to assess the functional outcomes after MAT using three different clinically‐relevant methods in a preclinical canine model. The study was designed to test the hypothesis that fresh meniscal‐osteochondral allograft transplantation would be associated with significantly better function and joint health compared with fresh‐viable or fresh‐frozen meniscus‐only allograft transplantations. Three months after meniscal release to induce meniscus‐deficient medial compartment disease, research hounds (n = 12) underwent MAT using meniscus allografts harvested from matched dogs. Three MAT conditions (n = 4 each) were compared: frozen meniscus–fresh‐frozen meniscal allograft with menisco‐capsular suture repair; fresh meniscus–fresh viable meniscal allograft (Missouri Osteochondral Preservation System (MOPS)‐preservation for 30 days) with menisco‐tibial ligament repair; fresh menisco‐tibial–fresh, viable meniscal‐tibial‐osteochondral allografts (MOPS‐preservation for 30 days) with menisco‐tibial ligament preservation and autogenous bone marrow aspirate concentrate on OCA bone. Assessment was performed up to 6 months after MAT. Pain, comfortable range of motion, imaging, and arthroscopic scores as well histological and cell viability findings were superior (P <.05) for the fresh menisco‐tibial group compared with the two other groups. Novel meniscal preservation and implantation techniques with fresh, MOPS‐preserved, viable meniscal‐osteochondral allografts with menisco‐tibial ligament preservation appears to be safe and effective for restoring knee function and joint health in this preclinical model. This has the potential to significantly improve outcomes after MAT. [ABSTRACT FROM AUTHOR]

Neck and low back pain are common among the adult human population and impose large social and economic burdens on health care and quality of life. Spine‐related disorders are also significant health concerns for canine companions with etiopathogeneses, clinical presentations, and diagnostic and therapeutic options that are very similar to their human counterparts. Historically, induced and spontaneous pathology in laboratory rodents, dogs, sheep, goats, pigs, and nonhuman primates have been used for study of human spine disorders. While each of these can serve as useful preclinical models, they all have inherent limitations. Spontaneously occurring spine disorders in dogs provide highly translatable data that overcome many of the limitations of other models and have the added benefit of contributing to veterinary healthcare as well. For this scoping review, peer‐reviewed manuscripts were selected from PubMed and Google Scholar searches using keywords: "intervertebral disc," "intervertebral disc degeneration," "biomarkers," "histopathology," "canine," and "mechanism." Additional keywords such as "injury," "induced model," and "nucleus degeneration" were used to further narrow inclusion. The objectives of this review were to (a) outline similarities in key features of spine disorders between dogs and humans; (b) describe relevant canine models; and (c) highlight the applicability of these models for advancing translational research and clinical application for mechanisms of disease, diagnosis, prognosis, prevention, and treatment, with a focus on intervertebral disc degeneration. Best current evidence suggests that dogs share important anatomical, physiological, histological, and molecular components of spinal disorders in humans, such that induced and spontaneous canine models can be very effective for translational research. Taken together, the peer‐reviewed literature supports numerous advantages for use of canine models for study of disorders of the spine when the potential limitations and challenges are addressed. [ABSTRACT FROM AUTHOR]

Articular cartilage injuries are a common source of joint pain and dysfunction. We hypothesized that pulsed electromagnetic fields (PEMFs) would improve growth and healing of tissue‐engineered cartilage grafts in a direction‐dependent manner. PEMF stimulation of engineered cartilage constructs was first evaluated in vitro using passaged adult canine chondrocytes embedded in an agarose hydrogel scaffold. PEMF coils oriented parallel to the articular surface induced superior repair stiffness compared to both perpendicular PEMF (p =.026) and control (p =.012). This was correlated with increased glycosaminoglycan deposition in both parallel and perpendicular PEMF orientations compared to control (p =.010 and.028, respectively). Following in vitro optimization, the potential clinical translation of PEMF was evaluated in a preliminary in vivo preclinical adult canine model. Engineered osteochondral constructs (∅ 6 mm × 6 mm thick, devitalized bone base) were cultured to maturity and implanted into focal defects created in the stifle (knee) joint. To assess expedited early repair, animals were assessed after a 3‐month recovery period, with microfracture repairs serving as an additional clinical control. In vivo, PEMF led to a greater likelihood of normal chondrocyte (odds ratio [OR]: 2.5, p =.051) and proteoglycan (OR: 5.0, p =.013) histological scores in engineered constructs. Interestingly, engineered constructs outperformed microfracture in clinical scoring, regardless of PEMF treatment (p <.05). Overall, the studies provided evidence that PEMF stimulation enhanced engineered cartilage growth and repair, demonstrating a potential low‐cost, low‐risk, noninvasive treatment modality for expediting early cartilage repair. [ABSTRACT FROM AUTHOR]

This study characterizes outcomes associated with subchondroplasty (SCP) versus SCP enhanced with platelet‐rich plasma (PRP) or bone marrow aspirate concentrate (BMC) treatment of impact‐induced subchondral bone marrow lesions (BML) using a validated preclinical canine model. With IACUC approval, purpose‐bred research hounds (n = 24) underwent arthroscopic impact injury (40 N) to both medial femoral condyles. At 3 months, functional assessments, arthroscopy, and magnetic resonance imaging (MRI) were performed. One knee in each dog (n = 24; n = 12 per endpoint) was randomly assigned to SCP with the other knee randomly assigned to SCP + PRP, SCP + BMC or sham injection (control) (n = 8 per group; n = 4 per endpoint). Dogs were evaluated at 6 and 12 months after treatment using functional assessments, radiography, arthroscopy, and MRI and humanely euthanatized at 6 or 12 months after treatment for histologic assessments. At 6 months post‐treatment, comfortable range‐of‐motion (CROM) was higher (p < 0.04) in SCP + PRP and SCP + BMC knees compared with controls. At 1 year post‐treatment, %Total Pressure Index was higher (p = 0.036) in SCP + BMC compared with controls, pain was lower (p < 0.05) in SCP + BMC and SCP + PRP compared with SCP and controls, and CROM was higher (p < 0.05) in SCP + BMC and SCP + PRP compared with SCP and controls. Knees treated with SCP + PRP and SCP + BMC had better (p < 0.05) MRI grades than SCP and controls. No statistically significant differences in arthroscopic or histologic pathology were noted. Clinical significance: Biologics added to SCP treatment may further enhance its beneficial effects by improving range‐of‐motion, pain severity, and limb loading through 1 year after treatment. However, these benefits must be considered alongside cost, logistics, and treatment availability. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:740‐746, 2020 [ABSTRACT FROM AUTHOR]

The dog is the most commonly used large animal model for the study of osteoarthritis. Optimizing methods for assessing cartilage health would prove useful in reducing the number of dogs needed for a valid study of osteoarthritis and cartilage repair. Twelve beagles had critical‐sized osteochondral defects created in the medial femoral condyle of both knees. Eight dogs had T1ρ and T2 magnetic resonance imaging (MRI) performed approximately 6 months after defect creation. Following MRI evaluations, all 12 dogs were humanely euthanatized and cartilage samples were obtained from the medial and lateral femoral condyles, medial and lateral tibial plateaus, trochlear groove, and patella for proteoglycan and collagen quantification. Equilibrium partitioning of an ionic contrast (EPIC)‐µCT was then performed followed by the histologic assessment of the knees. Correlations between T1ρ, T2, EPIC‐µCT and proteoglycan, collagen, and histology scores were assessed using a multivariate analysis accounting for correlations from samples within the same knee and in the same dog. Pearson's correlation coefficients were calculated to assess the strength of significant relationships. Correlations between µCT values and biochemical or histologic assessment were weak to moderately strong (0.09–0.41; p < 0.0001–0.66). There was a weak correlation between the T2 values and cartilage proteoglycan (−0.32; p = 0.04). The correlation between T1ρ values and cartilage proteoglycan were moderately strong (−0.38; p < 0.05) while the strongest correlation was between the T1ρ values and histological assessment of cartilage with a correlation coefficient of 0.58 (p < 0.0001). These data suggest that T1ρ shows promise for possible utility in the translational study of cartilage health and warrants further development in this species. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:368‐377, 2020 [ABSTRACT FROM AUTHOR]

Symptomatic chondral and osteochondral defects affect a large and growing number of patients. A safe and effective surgical treatment for large articular defects is osteochondral allograft (OCA) transplantation. One of the major causes of failure for OCA transplantation is loss of essential chondrocyte viability during the preservation and storage period. It is also possible that metabolic responses of the OCA when transitioning from storage temperature to body temperature may contribute to mechanisms causing failure. The present study was designed to compare MOPSSM‐preserved OCAs to those stored using the current standard of care (SOC) method with respect to metabolic responses when rewarmed for transplantation to and maintenance at body temperature (37°C). It was theorized that grafts stored using the MOPSSM protocol would maintain significantly higher chondrocyte viability and produce significantly lower levels of inflammatory mediators and degradative enzymes, and significantly higher levels of chemokines compared to grafts stored using the SOC protocol. Left over SOC and MOPSSM‐stored OCA tissues were collected after surgery, and cartilage explants were cultured for 6 days. Media was analyzed for biomarkers using commercially available assays. Cartilage from SOC grafts released significantly higher levels of PGE2, MMP‐1, MMP‐2, and MMP‐13, and significantly lower levels of IL‐8 and Gro‐α, compared to cartilage from MOPSSM‐stored grafts. Clinical significance: These data suggest that OCAs stored using the MOPSSM protocol have potentially less detrimental initial inflammatory and degradative responses to re‐warming for transplantation compared to OCAs stored using the current tissue bank protocols. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1530–1536, 2019. [ABSTRACT FROM AUTHOR]

Meniscus tears in the avascular region rarely functionally heal due to poor intrinsic healing capacity, frequently resulting in tear propagation, followed by meniscus deterioration. Recently, we have reported that time‐controlled application of connective tissue growth factor (CTGF) and transforming tissue growth factor β3 (TGFβ3) significantly improved healing of avascular meniscus tears by inducing recruitment and step‐wise fibrocartilaginous differentiation of mesenchymal stem/progenitor cells (MSCs). In this study, we investigated effects of the dose of CTGF and the release rate of TGFβ3 on avascular meniscus healing in our existing explant model. Our hypothesis was that dose and release rate of CTGF and TGFβ3 are contributing factors for functional outcome in avascular meniscus healing by stem cell recruitment. Low (100 ng/ml) and high (1,000 ng/ml) doses of CTGF as well as fast (0.46 ± 0.2 ng/day) and slow (0.29 ± 0.1 ng/day) release rates of TGFβ3 were applied to our established meniscus explant model for meniscus tears in the inner‐third avascular region. The release rate of TGFβ3 was controlled by varying compositions of poly(lactic‐co‐glycolic acids) (PLGA) microspheres. The meniscus explants were then cultured for 8 weeks on top of mesenchymal stem/progenitor cells (MSCs). Among the tested combinations, we found that a high CTGF dose and slow TGFβ3 release are most effective for integrated healing of avascular meniscus, demonstrating improvements in alignment of collagen fibers, fibrocartilaginous matrix elaboration and mechanical properties. This study may represent an important step toward the development of a regenerative therapy to improve healing of avascular meniscus tears by stem cell recruitment. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1555–1562, 2019. [ABSTRACT FROM AUTHOR]

This study compares serum and urine concentrations of relevant protein biomarkers among adult dogs with or without radiographic canine hip dysplasia (CHD). Adult (≥2 years of age), client‐owned dogs (n = 74) radiographically categorized as having at least "good" hips (n = 49) or having "mild," "moderate," or "severe" hip dysplasia (n = 25) by the Orthopedic Foundation for Animals (OFA). Urine and serum samples were obtained from each dog at a single time‐point and processed and analyzed for relevant protein biomarkers. Urinary concentrations of CTX‐II (p < 0.001) and TIMP‐1 (p = 0.002) were significantly lower in dogs with CHD compared to dogs with no CHD. ROC curve analyses were successful in establishing a panel of four biomarkers (urinary CTX‐I and II, serum MMP‐9, and serum PIICP) with high discriminatory capability for the presence or absence of hip dysplasia in adult dogs (AUC = 0.89). Urine and serum biomarkers can distinguish adult dogs with radiographic CHD from those with no CHD with a sensitivity of 0.95 and specificity of 0.77 using ROC analysis with AUC 0.89. Clinical Significance: This finding suggests that this simple, minimally invasive diagnostic technique has potential for discriminating dysplastic dogs from dogs with normal hips, with possible translational application to humans based on similar etiopathogenesis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1–5, 2019. [ABSTRACT FROM AUTHOR]

This study was designed to characterize metabolic responses of meniscal tissue explants to injury and inflammation. We hypothesized that impact injury and interleukin (IL‐1β) stimulation of meniscal explants would result in significant increases in matrix metalloproteinase (MMP) activity and relevant cytokine production compared to controls. Mature canine meniscal explants (n = 9/group) were randomly assigned to: (i) IL‐1β (0.1 ng/ml) treated (IL); (ii) 25% strain (25); (iii) 75% strain (75); (iv) 25% + IL‐1β (25IL); (v) 75% + IL‐1β (75IL); or (vi) 0% + no IL‐1β control (NC). Explants were impacted at 100 mm/s to 0%, 25%, or 75% strain and then cultured for 12 days with or without 0.1 ng/ml rcIL‐1β. Media were refreshed every 3 days and analyzed for MMP activity, ADAMTS‐4 activity, MMP‐1, MMP‐2, MMP‐3, GAG, NO, PGE2, IL‐6, IL‐8, MCP‐1, and KC concentrations. Treatment with IL‐1β alone significantly increased NO, PGE2, general MMP activity, IL‐6, IL‐8, KC, and MCP‐1 media concentrations compared to negative controls. Impact at 75% significantly increased PGE2, IL‐6, IL‐8, and KC media concentrations compared to negative controls. The combination of IL‐1β and 75% strain significantly increased production of PGE2 compared to IL‐1β or 75% strain alone. Impact injury to meniscal explants ex vivo is associated with increased production of pro‐inflammatory mediators and degradative enzyme activity, which are exacerbated by stimulation with IL‐1β. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2657–2663, 2018. [ABSTRACT FROM AUTHOR]

This study characterizes long‐term outcomes associated with subchondroplasty (SCP) treatment for impact‐induced subchondral bone marrow lesions (BML) using a validated pre‐clinical canine model. With IACUC approval, purpose‐bred research hounds (n = 16) underwent arthroscopic impact injury (40N) to both medial femoral condyles. At 3 months, functional assessments, arthroscopy, and MRI were performed and knees (n = 32) were randomly assigned to SCP (3 ml fluoroscopically guided percutaneous injection of AccuFill BSM into BML bone defects) or sham injection (Control). Dogs were assessed at 3, 6, 12, and 24 months after treatment using functional assessments, radiographic evaluation, arthroscopy, and MRI. Dogs were humanely euthanatized at 3, 6, 12, or 24 months after treatment for gross, microCT, and histologic assessments. All knees had focal articular cartilage defects with associated subchondral BMLs, as well as clinical dysfunction, 3 months after injury. At the 3 and 6 months, SCP knees showed more functional impairment than Control knees, however, these differences were not statistically significant. At 1‐ and 2‐year post‐treatment, function in SCP knees was better than in Control knees with range of motion being significantly (p < 0.05) better for SCP. Radiographic, arthroscopic, MRI, gross, microCT, and histologic findings matched the functional assessments well with Control being associated with better results at the two early time points and SCP being associated with better results at 1 and 2 years. Clinical significance: SCP treatment using calcium phosphate bone void filler was associated with an initial increase in pain and dysfunction followed by symptomatic benefits for up to 2 years after treatment for post‐traumatic femoral condyle BMLs in a preclinical canine model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2709–2717, 2018. [ABSTRACT FROM AUTHOR]

ABSTRACT: This Level II study assessed clinically relevant outcomes for repair of large, retracted infraspinatus tendons (ISTs) using a demineralized bone matrix (DBM) sponge (FlexiGraft) hydrated in platelet‐rich plasma (PRP) versus direct repair in a validated canine model. Adult research dogs (n = 10) were used. The IST was transected in each shoulder (n = 20) and randomized to direct repair or repair with DBM‐PRP interposition at 4 weeks posttransection. At 12 weeks postrepair, dogs were sacrificed, and the repair evaluated by magnetic resonance imaging (MRI), histology, and biomechanical testing. MRI and histology scores were significantly (p < 0.05) better in the DBM‐PRP shoulders. Biomechanical testing revealed significantly improved strength of the DBM‐PRP repairs at 5 and 10 mm of displacement, as well as for ultimate failure load. In this canine model of retracted IST repair, DBM‐PRP sponge hydrated in PRP was considered safe and effective. In addition, use of DBM‐PRP was associated with improved MRI and histologic appearance, and improved strength compared to direct repair. Clinical significance: Based on reported failure rates for repair of large, retracted rotator cuff tears, improving tendon‐to‐bone healing is critical. Use of DBM combined with PRP shows potential for addressing this critical clinical need. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:906–912, 2018. [ABSTRACT FROM AUTHOR]

ABSTRACT Due to the degradation of osteoarthritic (OA) cartilage in post-traumatic OA (PTOA), these tissues are challenging to study and manipulate in vitro. In this study, chondrocytes isolated from either PTOA (meniscal-release (MR) model) or normal (contralateral limb) cartilage of canine knee joints were used to form micropellets to assess the maintenance of the OA chondrocyte phenotype in vitro. Media samples from the micropellet cultures were used to measure matrix metalloproteinase (MMP), chemokine, and cytokine concentrations. Significant differences in matrix synthesis were observed as a function of disease with OA chondrocytes generally synthesizing more extracellular matrix with increasing time in culture. No donor dependent differences were detected. Luminex multiplex analysis of pellet culture media showed disease and time-dependent differences in interleukin (IL)-8, keratinocyte chemoattractant (KC)-like protein, MMP-1, MMP-2, and MMP-3, which are differentially expressed in OA. This memory of their diseased phenotype persists for the first 2 weeks of culture. These results demonstrate the potential to use chondrocytes from an animal model of OA to study phenotype alterations during the progression and treatment of OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:829-836, 2017. [ABSTRACT FROM AUTHOR]

ABSTRACT The objective of this study was to assess the safety and efficacy of intra-articular injections of hyaluronic acid (HA) versus saline for symptomatic treatment of osteoarthritis (OA). Twenty-five adult purpose-bred dogs underwent meniscal release of one knee. Clinical, arthroscopic, and radiographic signs of OA were confirmed in all dogs prior to treatment. Dogs were randomized into five groups: HA-1 ( n = 5), HA-3 ( n = 5), HA-5 ( n = 5), Saline-1 ( n = 5), and Saline-3 ( n = 5). Each dog received intra-articular injections of the respective substance into the affected knee at the pre-determined time points. Dogs were assessed for heat, swelling, and erythema after each injection and for lameness, pain, effusion, range of motion, kinetics, radiographic OA scoring, and arthroscopic scoring prior to treatment and for 6 months after injection. Dogs were then humanely euthanatized and the knees assessed grossly and histologically. Only mild heat, swelling, and/or erythema were noted in some dogs following injection and resolved within 1 week. Dogs treated with HA-1, HA-3, and HA-5 were significantly ( p < 0.05) better than dogs treated with Saline-1 and Saline-3 at the 4, 8, and 12 week time points based on at least one outcome measure. OA severity was not significantly different among groups at any time point, but increased in severity over time in all groups. Gross and histologic OA scores were not significantly different among groups. These data suggest the three HA injection protocols were safe, superior to saline for short-term amelioration of symptoms associated with chronic OA, and can be translated to human OA treatment. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1772-1779, 2016. [ABSTRACT FROM AUTHOR]

ABSTRACT Platelet rich plasma (PRP) is used to treat many musculoskeletal disorders. We used a canine model to determine the effects of multiple intra-articular injections of leukoreduced PRP (ACP) on anterior cruciate ligament healing, meniscal healing, and progression of osteoarthritis (OA). With Animal Care and Use Committee (ACUC) approval, 12 dogs underwent partial ACL transection and meniscal release in one knee. At weeks 1, 2, 3, 6, and 8 after insult, dogs were treated with intra-articular injections (2 ml) of either ACP ( n = 6) or saline ( n = 6). Dogs were assessed over 6 months to determine comfortable range of motion (CROM), lameness, pain, effusion, kinetics, and radiographic and arthroscopic assessments. At 6-month endpoint, dogs were assessed for ACL material properties and histopathology. Saline-treated dogs had significantly ( p < 0.04) more CROM loss, significantly ( p < 0.01) more pain, significantly ( p < 0.05) more severe lameness, significantly ( p < 0.05) lower function, and significantly ( p < 0.05) lower %Total Pressure Index in affected hindlimbs compared to ACP-treated dogs. Radiographic OA increased significantly ( p < 0.01) over time within each group. Arthroscopically, saline-treated knees showed moderate to severe synovitis, further ACL disruption, and medial compartment cartilage loss, and ACP-treated knees showed evidence of ACL repair and less severe synovitis. ACL material properties in ACP-treated knees were closer to normal than in saline-treated knees, however, the differences were not statistically significant. ACL histopathology was significantly ( p< 0.05) less severe in ACP-treated knees compared to saline-treated knees. Five intra-articular injections of leukoreduced PRP had beneficial effects for ACL healing, improved range of motion, decreased pain, and improved limb function for up to 6 months in this model. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:607-615, 2016. [ABSTRACT FROM AUTHOR]

ABSTRACT With limited availability of osteochondral allografts, tissue engineered cartilage grafts may provide an alternative treatment for large cartilage defects. An effective storage protocol will be critical for translating this technology to clinical use. The purpose of this study was to evaluate the efficacy of the Missouri Osteochondral Allograft Preservation System (MOPS) for room temperature storage of mature tissue engineered grafts, focusing on tissue property maintenance during the current allograft storage window (28 days). Additional research compares MOPS to continued culture, investigates temperature influence, and examines longer-term storage. Articular cartilage constructs were cultured to maturity using adult canine chondrocytes, then preserved with MOPS at room temperature, in refrigeration, or kept in culture for an additional 56 days. MOPS storage maintained desired chondrocyte viability for 28 days of room temperature storage, retaining 75% of the maturity point Young's modulus without significant decline in biochemical content. Properties dropped past this time point. Refrigeration maintained properties similar to room temperature at 28 days, but proved better at 56 days. For engineered grafts, MOPS maintained the majority of tissue properties for the 28-day window without clearly extending that period as it had for native grafts. These results are the first evaluating engineered cartilage storage. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:141-148, 2016. [ABSTRACT FROM AUTHOR]

ABSTRACT Development and validation of a large animal model for pre-clinical studies of intra-articular anterior cruciate ligament (ACL) reconstruction that addresses current limitations is highly desirable. The objective of the present study was to investigate a translational canine model for ACL reconstruction. With institutional approval, adult research hounds underwent arthroscopic debridement of the anteromedial bundle (AMB) of the ACL, and then either received a tendon autograft for 'hybrid double-bundle' ACL reconstruction ( n = 12) or no graft to remain ACL/AMB-deficient ( n = 6). Contralateral knees were used as non-operated controls ( n = 18) and matched canine cadaveric knees were used as biomechanical controls ( n = 6). Dogs were assessed using functional, diagnostic imaging, gross, biomechanical, and histologic outcome measures required for pre-clinical animal models. The data suggest that this canine model was able to overcome the major limitations of large animal models used for translational research in ACL reconstruction and closely follow clinical aspects of human ACL reconstruction. The 'hybrid double-bundle' ACL reconstruction allowed for sustained knee function without the development of osteoarthritis and for significantly improved functional, diagnostic imaging, gross, biomechanical, and histologic outcomes in grafted knees compared to ACL/AMB-deficient knees. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1171-1179, 2015. [ABSTRACT FROM AUTHOR]

Radiography, magnetic resonance imaging (MRI), and ultrasonography are commonly used for diagnosis of shoulder osteochondrosis and osteochondritis dissecans (OC/OCD) in dogs, however there is a lack of published information on the relative diagnostic sensitivities of these modalities. The purpose of this prospective study was to compare diagnostic sensitivities of these modalities for detecting shoulder OC/OCD in a group of dogs, using arthroscopy as the reference standard. Inclusion criteria were history and clinical findings consistent with osteochondrosis and/or osteochondritis dissecans involving at least one shoulder. With informed client consent, both shoulders for all included dogs were examined using standardized radiography, ultrasonography, MRI, and arthroscopy protocols. One of three veterinary surgeons recorded clinical and arthroscopic findings without knowledge of diagnostic imaging findings. One of two veterinary radiologists recorded diagnostic imaging findings without knowledge of clinical and arthroscopic findings. Eighteen client-owned dogs ( n = 36 shoulders) met inclusion criteria. Diagnostic sensitivity, specificity, and accuracy (correct classification rate) values for detecting presence or absence of shoulder osteochondrosis/osteochondritis dissecans were as follows: radiography (88.5%, 90%, 88.9%), ultrasonography (92%, 60%, 82.6%), and MRI (96%, 88.9%, 94.4%). Odds of a correct diagnosis for MRI were 3.2 times more than ultrasonography and two times more than radiography. For MRI detection of lesions, the sagittal T2 or PD-FAT SAT sequences were considered to be most helpful. For radiographic detection of lesions, the additional supinated-mediolateral and pronated-mediolateral projections were considered to be most helpful. Findings from the current study support more evidence-based diagnostic imaging recommendations for dogs with clinically suspected shoulder osteochondrosis or osteochondritis dissecans. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis remains a tremendous public health concern, both in terms of health-related quality of life and financial burden of disease. Translational research is a critical step towards understanding and mitigating the long-term effects of this disease process. Animal models provide practical and clinically relevant ways to study both the natural history and response to treatment of knee osteoarthritis. Many factors including size, cost, and method of inducing osteoarthritis are important considerations for choosing an appropriate animal model. Smaller animals are useful because of their ease of use and cost, while larger animals are advantageous because of their anatomical similarity to humans. This evidence-based review will compare and contrast several different animal models for knee osteoarthritis. Our goal is to inform the clinician about current research models, in order to facilitate the transfer of knowledge from the "bench" to the "bedside" [ABSTRACT FROM AUTHOR]

Tissue‐engineered osteochondral grafts have been synthesized from a variety of materials, with some success at repairing chondral defects in animal models. We hypothesized that in tissue‐engineered osteochondral grafts synthesized by bonding mesenchymal stem cell‐loaded hydrogels to a porous material, the choice of the porous scaffold would affect graft healing to host bone, and the quality of cell restoration at the hyaline cartilage surface. Bone marrow‐derived allogeneic mesenchymal stem cells were suspended in hydrogels that were attached to cylinders of porous tantalum metal, allograft bone, or a bioactive glass. The tissue‐engineered osteochondral grafts, thus created were implanted into experimental defects in rabbit knees. Subchondral bone restoration, defect fill, bone ingrowth‐implant integration, and articular tissue quality were compared between the three subchondral materials at 6 and 12 weeks. Bioactive glass and porous tantalum were superior to bone allograft in integrating to adjacent host bone, regenerating hyaline‐like tissue at the graft surface, and expressing type II collagen in the articular cartilage. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010 [ABSTRACT FROM AUTHOR]