Comparison of reamer irrigator aspirator (RIA) suspension versus bone marrow aspirate concentrate (BMC) for percutaneous treatment of long bone nonunions-A preclinical canine model.

OBJECTIVE: To compare the bone healing effects of percutaneously delivered bone marrow aspirate concentrate (BMC) versus reamer irrigator aspirator (RIA) suspension in a validated preclinical canine ulnar nonunion model. We hypothesized that BMC would be superior to RIA in inducing bone formation across a nonunion site after percutaneous application. The null hypothesis was that BMC and RIA would be equivalent. METHODS: A bilateral ulnar nonunion model (n= 6; 3 matched pairs) was created. Eight weeks after segmental ulnar ostectomy, RIA from the ipsilateral femur and BMC from the proximal humerus were harvested and percutaneously administered into either the left or right ulnar defect. The same volume (3 ml) of RIA suspension and BMC were applied on each side. Eight weeks after treatment, the dogs were euthanized, and the nonunions were evaluated using radiographic, biomechanical, and histologic assessments. RESULTS: All dogs survived for the intended study duration, formed radiographic nonunions 8 weeks after segmental ulnar ostectomy, and underwent the assigned percutaneous treatment. Radiographic and macroscopic assessments of bone healing at the defect sites revealed superior bridging-callous formation in BMC-treated nonunions. Histologic analyses revealed greater amount of bony bridging and callous formation in the BMC group. Biomechanical testing of the treated nonunions did not reveal any significant differences. CONCLUSION: Bone marrow aspirate concentrate (BMC) had important advantages over Reamer Irrigator Aspirator (RIA) suspension for percutaneous augmentation of bone healing in a validated preclinical canine ulnar nonunion model based on clinically relevant radiographic and histologic measures of bone formation.

Spindle cell cutaneous epitheliotropic T-cell lymphoma in an American Bulldog.

An 8-year-old American Bulldog developed coalescing exophytic bulbous nodules that grew rapidly on the left pinna and a single cutaneous mass on the left flank. Histological examination of the pinnal biopsy by a diagnostic laboratory revealed a densely cellular neoplasm with haphazardly arranged round to spindle cells with high mitotic activity and epitheliotropism. The initial diagnosis was a poorly differentiated malignant neoplasm with differential diagnoses including melanoma, tumour of histiocytic origin and, less likely, a pleomorphic lymphoma. A panel of melanoma immunohistochemical markers and immunolabelling for CD18 were pursued. Neoplastic cells were immunopositive for CD18 but negative for Melan-A, PNL2, TRP-1 and TRP-2, suggestive of a histiocytic tumour or lymphoma. The left ear masses recurred, and more masses developed on the body. The pinnectomized ear was submitted to the University of Missouri Veterinary Medical Diagnostic Laboratory. Similar cells were seen and were immunolabelled for CD18 and CD3 but were immunonegative for SOX10, CD79a and CD20. PCR for antigen receptor rearrangements revealed a clonal rearrangement of T-cell receptor gamma. These findings enabled a final diagnosis of epitheliotropic T-cell lymphoma with spindle cell morphology. Lymphoma should be considered as a potential differential diagnosis for cutaneous nodules of spindle cell morphology and lymphocytic immunohistochemical markers should be included in diagnostic panels.

Making the Case for Hyperosmolar Saline Arthroscopic Irrigation Fluids: A Systematic Review of Basic Science, Translational, and Clinical Evidence.

Commonly used isotonic arthroscopic irrigation fluids, such as normal saline or lactated Ringer's, were initially formulated for intravenous administration so they do not replicate the physiologic properties of healthy synovial fluid. Synovial fluid plays an important role in regulating joint homeostasis such that even transient disruptions in its composition and physiology can be detrimental. Previous studies suggest that hyperosmolar solutions may be a promising alternative to traditional isotonic fluids. This manuscript sought to systematically review and synthesize previously published basic science, translational, and clinical studies on the use of hyperosmolar arthroscopic irrigation fluids to delineate the optimal fluid for clinical use. A systematic literature search of MEDLINE/PubMed and Embase databases was performed in accordance with Preferred Reporting Items for Systemic Reviews and Meta-analyses (PRISMA) guidelines. The search phrases were: ("cartilage" AND "hyperosmolar"); ("arthroscopy" OR "arthroscopic" AND "hyperosmolar"). The titles, abstracts, and full texts were screened for studies on hyperosmolar solutions and articular cartilage. Study quality was assessed, and relevant data were collected. A meta-analysis was not performed due to study heterogeneity. A risk of bias assessment was performed on the included translational and clinical studies. There were 10 basic science studies, 2 studies performed in translational animal models, and 2 clinical studies included in this review. Of the basic science studies, 7 utilized a mechanical injury model. The translational studies were carried out in the canine shoulder and equine stifle (knee) joint. Clinical studies were performed in the shoulder and knee. Multiple basic science, translational, and clinical studies highlight the short-term safety, cost-effectiveness, and potential benefits associated with use of hyperosmolar solutions for arthroscopic irrigation. Further work is needed to develop and validate the ideal formulation for a hyperosmolar irrigation solution with proven long-term benefits for patients undergoing arthroscopic surgeries.

Head and neck squamous cell carcinoma with heterotopic ossification, lymphovascular invasion, and nodal and pulmonary metastases in a 23-year-old Morgan gelding.

Primary squamous cell carcinoma of the head and neck occurs in the skin or squamous epithelial lining tissues of the oral cavity, pharynx, larynx, and sinonasal tract. Although it is a common tumor in horses, distant metastatic spread to the lung is rare. This report describes a case of metastatic pulmonary squamous cell carcinoma in a 23-year-old Morgan gelding. The clinical signs displayed by this gelding in some ways mimicked the typical presentation of equine multinodular pulmonary fibrosis or thoracic lymphoma. The postmortem diagnosis in this case was head and neck squamous cell carcinoma, but a primary site of origin could not be ascertained. Cancer-associated heterotopic ossification (HO) was also identified in this case; this is an exceedingly rare finding with equine pulmonary neoplasia. Key clinical message: Careful physical examination should be undertaken in all horses presenting with clinical signs of intrathoracic disease. Clinical and radiographic abnormalities in this case of pulmonary metastatic disease resembled some of those associated with interstitial pneumonia. Rarely encountered in domestic animal species, there has been only 1 previous report of HO in a case of oronasal carcinoma in a horse.

Carcinome épidermoïde de la tête et du cou avec ossification hétérotopique, envahissement lymphovasculaire et métastases ganglionnaires et pulmonaires chez un hongre Morgan de 23 ans. Le carcinome épidermoïde primitif de la tête et du cou survient dans la peau ou les tissus épithéliaux squameux de la cavité buccale, du pharynx, du larynx et du tractus naso-sinusien. Bien qu'il s'agisse d'une tumeur courante chez les chevaux, la propagation métastatique à distance au poumon est rare. Ce rapport décrit un cas de carcinome épidermoïde pulmonaire métastatique chez un hongre Morgan de 23 ans. Les signes cliniques présentés par ce hongre imitaient à certains égards la présentation typique de la fibrose pulmonaire multinodulaire équine ou du lymphome thoracique. Le diagnostic post-mortem dans ce cas était un carcinome épidermoïde de la tête et du cou, mais un site d'origine primaire n'a pas pu être déterminé. L'ossification hétérotopique associée au cancer (HO) a également été identifiée dans ce cas; il s'agit d'une découverte extrêmement rare avec la néoplasie pulmonaire équine.Message clinique clé :Un examen physique attentif doit être entrepris chez tous les chevaux présentant des signes cliniques de maladie intrathoracique. Les anomalies cliniques et radiographiques dans ce cas de maladie pulmonaire métastatique ressemblaient à certaines de celles associées à la pneumonie interstitielle. Rarement rencontré chez les espèces animales domestiques, il n'y a eu qu'un seul signalement antérieur d'HO dans un cas de carcinome oronasal chez un cheval.(Traduit par Dr Serge Messier).

Alveolar echinococcosis in a dog in Missouri, USA.

A 10-y-old, castrated male Boxer dog that was born and had lived in Missouri without any travel history to other states, except for a few trips to Kansas, was presented with a distended abdomen and declined health. Ultrasonographic examination revealed a large hepatic mass, and the dog was euthanized. A postmortem examination revealed that the left liver lobes were largely replaced by a white-to-tan multilobular mass with a cobblestone surface. The lesion also involved the diaphragm. Histologically, hepatic architecture was effaced by large areas of necrosis with numerous, ≤0.2-cm, cystic structures that stained positively with periodic acid-Schiff stain and contained calcareous corpuscles. Gross and microscopic hepatic lesions were compatible with alveolar echinococcosis (AE) caused by Echinococcus multilocularis. PCR examination confirmed E. multilocularis, and results from genotyping were consistent with the E4 haplotype. To our knowledge, this is only the second canine AE case and the third pet dog that has been confirmed to be infected by E. multilocularis in the contiguous United States. E. multilocularis is a serious health risk for both pet dogs and humans.

The use of gold nanoparticles in improving ACL graft performance in an ovine model.

Surgical repair of the anterior cruciate ligament (ACL) can involve autograft or allograft materials. Allografts are typically chosen to avoid donor site morbidity associated with autografts harvest, but they can also result in a prolonged inflammatory period and delayed graft remodeling when compared to autografts. The aim of this study was to investigate the use of gold nanoparticles (AuNPs) conjugated to allografts to determine if AuNPs can reduce inflammation and enhance graft remodeling in an ovine model. Six sheep had their ACL surgically removed and replaced with a decellularized human gracilis tendon. Three of the sheep received grafts conjugated with 20 nm gold nanoparticles, while three of the sheep received grafts without the gold nanoparticles. The sheep were sacrificed 8 weeks after ACL reconstruction. Immediately following sacrifice, joint fluid was collected for cytology. Semi-quantitative histological scoring of the bone tunnel portion and the intra-articular portion of the grafts were performed independently along with descriptive analysis of histologic changes and quantitative analysis of revascularization. The results demonstrated that AuNP experimental grafts had an overall better histological scores than the non-AuNPs graft. The AuNPs grafts exhibited decreased inflammation in the bone tunnel portion of the graft, the intra-articular portion of the graft, and in the synovial fluid cell count. Overall, the results demonstrated that the grafts conjugated with nanoparticles have the potential to be influence inflammation and overall remodeling response.

Does Irrigating While Drilling Decrease Bone Damage?

Background: Heat generated during bone drilling may be associated with thermal necrosis and direct damage, leading to complications after surgery. This preclinical study evaluates the in vivo effects of saline irrigation, drilling device type, and device sharpness on heat generation and bone damage in viable cortical bone. Methods: Bicortical drilling of each tibial diaphysis from anesthetized research dogs was performed to evaluate temperature and bone damage using five different devices with or without saline irrigation. Results: Saline irrigation and sharp drill bits were associated with smaller temperature increases and less acute osteonecrosis. Conventional trocar tip Kirschner wires were associated with the largest temperature increase and the most acute osteonecrosis changes. Conclusion: The use of saline irrigation during bone drilling reduces temperature change and osteonecrosis. Furthermore, we recommend that the use of dull drill bits or standard tip Kirschner wires be avoided. Lastly, drill bit design can directly contribute to bone damage during drilling. Clinical Relevance: This study provides in vivo data from a preclinical model to validate the benefits of saline irrigation and sharp drill bits during bone drilling to regulate increases in temperature and decrease associated osteonecrosis. Risk for early implant loosening and poor surgical outcome is influenced by thermal osteonecrosis of bone such that consistent use of saline irrigation, sharp drill bits, and optimized designs may have important clinical advantages. Level of Evidence: II.

Histologic evidence for a humoral immune response in synovitis associated with cranial cruciate ligament disease in dogs.

OBJECTIVE: To investigate histopathological features of synovium from dogs with cranial cruciate ligament disease (CCLD) to seek mechanisms of osteoarthritis (OA) associated with CCLD. STUDY DESIGN: Retrospective, single-institution case series. ANIMALS: Thirty client-owned dogs. METHODS: Synovial biopsies (n = 30) obtained from stifles with CCLD were assessed by using two synovitis histopathology grading systems (Krenn and Hospital for Special Surgery [HSS]). The Krenn synovitis score was interpreted as "no synovitis," "low-grade," or "high-grade," while inflammatory subtype (low, mixed, or high) was determined by a computational algorithm within the HSS system. Comparison of synovitis scores was based on degree of CCL rupture and presence of meniscal tears. RESULTS: Histopathological changes and synovitis scores were similar regardless of degree of rupture (partial n = 5, complete n = 25) or presence of meniscal injury (n = 12) and were characterized by hyperplastic and lymphoplasmacytic synovitis with increased vascularity (30/30) and the presence of hemosiderin deposits (28/30), binucleated plasma cells (28/30), mucoid change (25/30), and Mott cells (16/30). Thirteen (43%) specimens were consistent with high-grade synovitis according to the Krenn system, while 11 (37%) specimens fit into the high-inflammatory subtype with the HSS system. CONCLUSION: Synovitis associated with canine CCLD in this study population was lymphoplasmacytic and was often highly inflammatory, with the presence of cells pertaining to humoral immunity. Humoral immune responses may play key roles in the synovitis associated with CCLD. CLINICAL SIGNIFICANCE: Modulation of biological factors that provoke humoral immune responses may mitigate symptoms of OA that persist and progress even after surgical treatment of CCLD in dogs.

Systematic Review of Osteochondral Allograft Transplant Immunology: How We Can Further Optimize Outcomes.

Despite the growing success for osteochondral allograft (OCA) transplantation in treating large articular cartilage lesions in multiple joints, associated revision and failure rates are still higher than desired. While immunorejection responses have not been documented, the effects of the host's immune responses on OCA transplantation failures have not been thoroughly characterized. The objective of this study was to systematically review clinically relevant peer-reviewed evidence pertaining to the immunology of OCAs to elucidate theragnostic strategies for improving functional graft survival and outcomes for patients undergoing OCA transplantation. This systematic review of Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, MEDLINE, PubMed, and EMBASE suggests that host immune responses play key roles in incorporation and functional survival of OCA transplants. OCA rejection has not been reported; however, graft integration through creeping substitution is reliant on host immune responses. Prolonged inflammation, diminished osteogenic potential for healing and incorporation, and relative bioburden are mechanisms that may be influenced by the immune system and contribute to undesirable outcomes after OCA transplantation. Based on the safety and efficacy of OCA transplantation and its associated benefits to a large and growing patient population, basic, preclinical, and clinical osteoimmunological studies on OCA transplantation that comprehensively assess and correlate cellular, molecular, histologic, biomechanical, biomarkers, diagnostic imaging, arthroscopic, functional, and patient-reported outcome measures are of high interest and importance.

Effects of cyclic compression on intervertebral disc metabolism using a whole-organ rat tail model.

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-1ß, 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.

Comparison of meniscal allograft transplantation techniques using a preclinical canine model.

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.

Unicompartmental bipolar osteochondral and meniscal allograft transplantation is effective for treatment of medial compartment gonarthrosis in a canine model.

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.

Clinical Application of the Basic Science of Articular Cartilage Pathology and Treatment.

The joint is an organ with each tissue playing critical roles in health and disease. Intact articular cartilage is an exquisite tissue that withstands incredible biologic and biomechanical demands in allowing movement and function, which is why hyaline cartilage must be maintained within a very narrow range of biochemical composition and morphologic architecture to meet demands while maintaining health and integrity. Unfortunately, insult, injury, and/or aging can initiate a cascade of events that result in erosion, degradation, and loss of articular cartilage such that joint pain and dysfunction ensue. Importantly, articular cartilage pathology affects the health of the entire joint and therefore should not be considered or addressed in isolation. Treating articular cartilage lesions is challenging because left alone, the tissue is incapable of regeneration or highly functional and durable repair. Nonoperative treatments can alleviate symptoms associated with cartilage pathology but are not curative or lasting. Current surgical treatments range from stimulation of intrinsic repair to whole-surface and whole-joint restoration. Unfortunately, there is a relative paucity of prospective, randomized controlled, or well-designed cohort-based clinical trials with respect to cartilage repair and restoration surgeries, such that there is a gap in knowledge that must be addressed to determine optimal treatment strategies for this ubiquitous problem in orthopedic health care. This review article discusses the basic science rationale and principles that influence pathology, symptoms, treatment algorithms, and outcomes associated with articular cartilage defects in the knee.

Intestinal echinococcosis in a dog from Missouri.

CASE DESCRIPTION: A 17-week-old 14.4-kg (31.7-lb) female German Shepherd Dog from Missouri with a history of multiple intermittent episodes of vomiting and diarrhea underwent exploratory celiotomy. CLINICAL FINDINGS: At the time of surgery, the dog was bright, alert, and responsive, with a tender abdomen and palpable mesenteric lymph nodes. Hematologic data revealed mild leukocytosis, mild hypoproteinemia, and mild hypoalbuminemia. Moderate petechiation of the jejunal serosa and prominent mesenteric lymph nodes, but no palpable obstructions, were found during surgery. Jejunal and lymph node biopsies were performed; histologic examination revealed multiple segments of adult cestodes up to 700 µm long in the jejunum. Segments had a scolex and contained approximately 30- to 35-µm-diameter ova, morphologically compatible with Echinococcus spp. Fecal flotation revealed numerous proglottids and ova similar to those recognized histologically. Results of PCR assays confirmed Echinococcus multilocularis of E4 haplotype (a European strain). TREATMENT AND OUTCOME: Praziquantel (5 mg/kg [2.3 mg/lb], SC, once) was administered after surgery; treatments after hospital discharge included praziquantel (10 mg/kg [4.5 mg/lb], PO, once). No proglottids or ova were observed by fecal flotation after the treatments. The dog remained healthy without gastrointestinal signs 1 year later. CLINICAL RELEVANCE: The dog of this report had no travel history outside the state of Missouri. To the authors' knowledge, this is the first report of intestinal E multilocularis infection in a pet dog in the contiguous United States and first detection of a European strain of E multilocularis in this country. Findings suggested possible establishment of a European strain of this zoonotic pathogen in the contiguous United States.

Comparison of biologic scaffolds for augmentation of partial rotator cuff tears in a canine model.

BACKGROUND: This study was designed to test the hypothesis that biologic scaffold augmentation of articular-sided partial-thickness supraspinatus tendon tears would be associated with superior functional, imaging, biomechanical, and histologic properties compared with untreated tears in a preclinical canine model. METHODS: With Institutional Animal Care and Use Committee approval, dogs (n = 16) underwent half-thickness resection of the articular portion of the supraspinatus tendon (SST). Defects were treated by débridement (DB) (n = 8) or scaffold augmentation on the bursal side using amnion matrix cord scaffold (AM) (n = 8), decellularized human dermal allograft (AF) (n = 8), or bovine collagen patch (RMP) (n = 8). Control dogs (n = 4; 8 normal shoulders) were included. Assessments included lameness, function, comfortable shoulder range of motion (CROM), pain, ultrasonography, magnetic resonance imaging (MRI), arthroscopy, gross examination, biomechanical testing, and histopathology. RESULTS: At 3 months, CROM was significantly lower and pain significantly higher in DB compared with all other groups. At 6 months, CROM was significantly lower and pain significantly higher in RMP compared with AM and AF, and AM and AF showed significantly less thickening than DB and RMP. AF had the least severe MRI pathology and AM had significantly less MRI pathology than DB. AF SSTs and biceps tendons showed the least severe histopathology, and AM SSTs showed significantly less histopathology than DB and RMP SSTs. CONCLUSION: Biologic scaffolds can be effective in augmenting healing of articular-sided partial-thickness SST tears when compared with débridement in a preclinical canine model. Decellularized human dermal allograft and amnion matrix cord may have advantages over the bovine collagen patch for use in this indication.

Patellar Bone-Tendon-Bone Autografts versus Quadriceps Tendon Allograft with Synthetic Augmentation in a Canine Model.

Patellar bone-tendon-bone (pBTB) autografts are often considered the "gold standard" for complete anterior cruciate ligament (ACL) reconstruction and are also associated with significant complications and early-onset knee osteoarthritis (OA). A novel quadriceps tendon allograft with synthetic augmentation, or "internal brace" (QTIB), has been reported to have potential advantages for ACL reconstruction based on animal model data. In this preclinical canine comparison study, we hypothesized that QTIB allograft compared with pBTB autograft would provide superior durability for knee stability, function, and prevention of OA. Under approval from our Institutional Animal Care and Use Committee, adult purpose-bred research hounds (n = 10) underwent arthroscopic complete transection of the ACL followed by either an arthroscopic-assisted all-inside ACL reconstruction using the QTIB allograft (n = 5) or pBTB autograft (n = 5). Contralateral knees were used as nonoperated controls (n = 10). Radiographic and arthroscopic assessments were performed at 2 and 6 months, respectively, after surgery. Anterior drawer, internal rotation, lameness, kinetics, pain, effusion, and comfortable range of knee motion were measured at 2, 3, and 6 months. Biomechanical and histologic assessments were performed at 6 months. All reconstructed knees were stable and had intact ACL grafts 6 months after surgery. At 6 months, QTIB reconstructed knees had significantly less lameness, lower pain, less effusion, and increased range of motion when compared with BTB knees (p < 0.05). BTB knees had significantly higher radiographic OA scores than QTIB knees at 6 months (p < 0.05). Superior outcomes associated with QTIB allograft may be due to the lack of donor site morbidity, the use of a robust tendon graft, and/or protection of the graft from the synthetic augmentation. Robust tendon grafts combined with a synthetic internal brace and platelet-rich plasma (PRP) may allow for more rapid and robust tendon-bone healing and graft "ligamentization," which protects the graft from early failure and rapid OA development that can plague commonly-used allografts.

Enhanced Subchondroplasty Treatment for Post-Traumatic Cartilage and Subchondral Bone Marrow Lesions in a Canine Model.

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.

Protein biomarkers in serum and urine for determining presence or absence of hip dysplasia in a canine model.

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.

Histologic assessment of ligament vascularity and synovitis in dogs with cranial cruciate ligament disease.

OBJECTIVE: To assess the relationship between histologic degeneration of cranial cruciate ligaments (CCLs) and severity of synovitis and ligament vascularity. SAMPLE: CCL and synovium from 59 stifle joints (53 dogs). PROCEDURES: CCL and synovium specimens were obtained from stifle joints of juvenile (15 joints; 12 dogs) and adult (25 joints; 22 dogs) dogs with intact CCLs and dogs with CCL rupture (rCCL; 19 joints; 19 dogs). Vascular density and degenerative changes of the CCL core region and severity of synovitis were semiquantitatively evaluated. Relationships were analyzed by use of a random effects model to account for correlated specimens. RESULTS: Mean ± SD modified Bonar scores (scale, 0 to 9) of adults (4.85 ± 0.44) and dogs with rCCL (5.69 ± 0.49) were significantly higher than scores of juveniles (1.13 ± 0.55). Vascularity scores (scale, 0 to 3) were significantly higher for juveniles (3.00 ± 0.24) than for adults (1.53 ± 0.27) and dogs with rCCL (0.78 ± 0.23). Synovitis scores were not significantly different among groups. There was a significant negative relationship between modified Bonar scores and vascularity scores for juveniles and adults and for adults and dogs with rCCL when controlling for age, but there was not a significant relationship between modified Bonar scores and synovitis scores. There was a significant relationship between modified Bonar scores and body weight of adults. CONCLUSIONS AND CLINICAL RELEVANCE: Poor blood supply to the core region could be an important underlying condition for spontaneous degeneration of the CCL in at-risk dogs.

Evaluation of a Novel Degradable Synthetic Biomaterial Patch for Augmentation of Tendon Healing in a Large Animal Model.

Tendon injury is common in sports. The standard of care (SOC) for tendon repair is surgical treatment. However, restored tendons often lack complete strength and functionality, and surgical repair is often unsuccessful. This controlled laboratory study investigates the healing of an Artelon patch (AP)-augmented tendon versus tendon repair alone in a preclinical canine patellar tendon defect model. Full-thickness proximal and distal flap defects were created in the patella tendons of eight purpose-bred research mongrel dogs. Dogs were randomly allocated into either the AP-augmented repair group or the SOC group (N = 8; four knees per group). Outcomes measures included limb function and pain; range of motion (ROM) and ultrasound assessment at 2, 4, and 8 weeks; and measurements of elongation, biomechanical testing, and histology at 8 weeks. Data were compared for statistically significant differences to preoperative measures and between groups (p < 0.05). The AP group had higher limb function scores compared with the SOC group at 2, 4, and 8 weeks, with statistically significant differences observed at 2 weeks (AP: 7.1 ± 1.4, SOC: 5.5 ± 0.4, p < 0.05) and 8 weeks (AP: 9.5 ± 0.7, SOC: 7.0 ± 0.9, p < 0.05). The ROM was significantly higher for the AP group at 4 weeks (AP: 105 degrees ± 4, SOC: 89 degrees ± 5, p < 0.05). Pain scores were statistically significantly lower in the AP group at 4 (AP: 0.6 ± 0.5, SOC: 2.2 ± 0.5) and 8 weeks (p < 0.05 for both comparisons). All animals in the AP group displayed full bridging tissue at week 4, while most animals of the SOC group displayed full bridging by week 8. Minimal tendon elongation was observed in both groups. Significantly more force was required to elongate tendons in the AP group compared with the SOC group (p < 0.05). Animals with AP-augmented tendon repair show an earlier regain of function, earlier regain of range of movement, less postoperative pain, and improved tendon strength when compared with animals treated with tendon repair alone.