Prevalence of presumed endplate junction failure at the lumbosacral intervertebral junction in dogs on computed tomography.

Lumbosacral intervertebral disc herniation (IVDH) is a common cause of lower back pain in dogs and humans. In humans, the vertebral endplate to annulus fibrosus (AF) attachment was implicated as an alternative failure site besides rupture through the dorsal AF (AFF). Endplate junction failure (EPJF) is characterized by IVDH, accompanied by endplate irregularities (type A), rim avulsions (type B), or larger bony avulsions on one (type C) or both endplates (type D), associated with an adjacent endplate defect. This retrospective study reports the CT prevalence of presumed EPJF in dogs and its associations with signalment and other lumbosacral CT abnormalities. CT scans, including the lumbosacral spine of dogs obtained at two institutions, were assessed, yielding 324 scans. Presumed EPJF was found in 69 dogs (21%) and AFF in 68 dogs (21%), commonly at the caudal endplate of the last lumbar vertebra (71%). The remaining 187 dogs did not show presumed EPJF or AFF. Presumed EPJF type A occurred in 49/69, type B in 19/69, and type C in 1/69 dogs. Univariable logistic regression showed that presumed EPJF was associated with significantly higher IVDH grades than AFF. In the multiple regression model, presumed EPJF and AFF remained associated with increasing age and spondylosis deformans. Presumed EPJF was associated with vertebral endplate sclerosis and AFF with zygapophyseal joint osteoarthritis. In conclusion, presumed EPJF was observed on CT in 21% of dogs with lumbosacral IVDH. Prospective studies correlating EPJF on CT with clinical, surgical, and histopathological findings are needed for a better understanding of the underlying pathology and clinical relevance.

Fast three-dimensional contrast-enhanced magnetic resonance angiography of the canine lumbar spinal cord vascular supply: A feasibility study.

Magnetic resonance angiography (MRA) is the noninvasive spinal cord vascular imaging modality of choice in human medicine. The aim of this exploratory, prospective, descriptive study was to assess the feasibility of fast three-dimensional (3D) contrast-enhanced (CE) MRA for visualization of spinal vascular structures in the canine lumbar region. Fourteen canine patients weighing > 5 kg were included. The lumbar arteries were consistently visualized (14/14;100%). Spinal arteries, radicular branches, great radicular artery (of Adamkiewicz), ventral spinal artery, and dorsal spinal arteries were not visualized (0/14;0%). The internal vertebral venous plexus was visualized in 11 of 14 (79%) dogs. Overall, the results of this study show that fast 3D CE-MRA of the lumbar region in dogs is feasible. However, the smaller arteries responsible for the spinal cord vascular supply were not visualized in this study.

Presumed cholesterinic granulomas detected on CT in horses are associated with increased lateral ventricle height and age.

Cholesterinic granulomas are mass-like lesions that form at the choroid plexus of the ventricular system. Large cholesterinic granulomas within the lateral ventricles have been reported to cause severe neurological signs. However, little data are available about their prevalence or appearance in the overall population. The objective was to report the prevalence of presumed cholesterinic granulomas on CT in a population of horses, and investigate associations between presumed cholesterinic granuloma presence, lateral ventricle size, age, and neurological signs. The study was cross sectional, CT scans of the head were assessed for presumed cholesterinic granuloma presence and size, and lateral ventricle height. Computed tomography findings and clinical information were compared using nonparametric testing. Computed tomography scans of 139 horses were included. Presumed cholesterinic granulomas were found in 22 horses (15.8%), nine were unilateral and 13 bilateral. A significant increase in prevalence was observed with age (P < .0001), with 38% of horses over 15 years old affected. The median volume of presumed cholesterinic granulomas was 242 mm3 with a range from 51 to 2420 mm3 . The mean lateral ventricle height was significantly increased in horses with presumed cholesterinic granulomas present (P = .004), with a median of 7.3 mm compared to 4.9 mm without. Neurological signs were not associated with presumed cholesterinic granuloma presence or lateral ventricle height. Fourth ventricle mineralizations were found in seven horses, which may represent cholesterinic granulomas. In conclusion, presumed cholesterinic granulomas occurred in a large proportion of the examined population and are associated with increased lateral ventricle dilation and advanced age.

Case report: Radiofrequency-induced thermal burn injury in a dog after magnetic resonance imaging.

A 10-year-old male Shar-Pei was referred for lethargy and proprioceptive deficits of the left thoracic limb. An magnetic resonance imaging (MRI) examination of the cervical spinal column and the brain was performed. The MRI examination of the brain was normal. A left-sided C3-C4 intervertebral disc extrusion with spinal cord compression was diagnosed. Medical treatment was elected. Within a week after the MRI examination, the dog presented with deep partial-thickness skin burn wounds in both axillae. Since the specific absorption rate had not exceeded the safety limits during any of the scans and no other procedures or circumstances were identified that could possibly have resulted in burn injuries, the thermal burn injuries were diagnosed as radiofrequency (RF) burns. The wounds healed by secondary intent over the next month. RF burns are the most reported complication in humans undergoing MRI but have not been reported in veterinary patients. Clinicians and technicians should consider the potential risk for RF burns in veterinary patients and take precautions regarding positioning of the patient and take notice of any signs of burn injury when performing follow-up examinations.

Automatic grading of intervertebral disc degeneration in lumbar dog spines.

Background: Intervertebral disc degeneration is frequent in dogs and can be associated with symptoms and functional impairments. The degree of disc degeneration can be assessed on T2-weighted MRI scans using the Pfirrmann classification scheme, which was developed for the human spine. However, it could also be used to quantify the effectiveness of disc regeneration therapies. We developed and tested a deep learning tool able to automatically score the degree of disc degeneration in dog spines, starting from an existing model designed to process images of human patients. Methods: MRI midsagittal scans of 5991 lumbar discs of dog patients were collected and manually evaluated with the Pfirrmann scheme and a modified scheme with transitional grades. A deep learning model was trained to classify the disc images based on the two schemes and tested by comparing its performance with the model processing human images. Results: The determination of the Pfirrmann grade showed sensitivities higher than 83% for all degeneration grades, except for grade 5, which is rare in dog spines, and high specificities. In comparison, the correspondent human model had slightly higher sensitivities, on average 90% versus 85% for the canine model. The modified scheme with the fractional grades did not show significant advantages with respect to the original Pfirrmann grades. Conclusions: The novel tool was able to accurately and reliably score the severity of disc degeneration in dogs, although with a performance inferior than that of the human model. The tool has potential in the clinical management of disc degeneration in canine patients as well as in longitudinal studies evaluating regenerative therapies in dogs used as animal models of human disorders.

Towards a flexible and personalised development of veterinarians and veterinary nurses working in a companion animal referral care setting.

In the Netherlands, the demand for veterinarians and veterinary nurses (VNs) working within referral care is rapidly growing and currently exceeds the amount of available board-certified specialists. Simultaneously, a transparent structure to guide training and development and to assess quality of non-specialist veterinarians and VNs working in a referral setting is lacking. In response, we developed learning pathways guided by an entrustable professional activity (EPA) framework and programmatic assessment to support personalised development and competence of veterinarians and VNs working in referral settings. Between 4 and 35 EPAs varying per discipline (n = 11) were developed. To date, 20 trainees across five disciplines have been entrusted. Trainees from these learning pathways have proceeded to acquire new EPAs in addition to their already entrusted set of EPAs or progressed to specialist training during (n = 3) or after successfully completing (n = 1) the learning pathway. Due to their outcome-based approach, the learning pathways support flexible ways of development.

Computed tomographic characteristics of presumed normal canine abdominal lymph nodes.

Though identification of lymph nodes is essential in staging cancer patients, little has been reported about the CT features of canine abdominal lymph nodes. The purpose of this retrospective study was to describe the visibility, location, and characteristics of abdominal lymph nodes in abdominal CT studies of dogs considered unlikely to have lymphadenopathy. The relationship between the number of identified lymph nodes and intraabdominal fat ranking, body weight, and slice thickness was also investigated. A total of 19 dogs were included. At least two jejunal lymph nodes and both left and right medial iliac lymph nodes were identified in all dogs. Colic lymph nodes were not identified in any of the dogs. Visualization of all other lymph nodes varied. There were significantly more lymph nodes visible in dogs with more intraabdominal fat (P < 0.0001). No correlation between the number of identified lymph nodes and body weight (P = 0.64) or slice thickness (P = 0.76) was found. Though most of all identified lymph nodes had an elongated shape, a rounded shape was most common in splenic, pancreaticoduodenal, renal, ileocolic and caudal mesenteric lymph nodes. Most lymph nodes had a homogeneous structure before and following the intravenous administration of contrast medium. Some lymph nodes had a slightly irregular structure or were relatively more hyper attenuating in the periphery than centrally before and/or after contrast administration. Mean attenuation before contrast was 37 Hounsfield Units (HU) (range 20-52 HU), and 109 HU after contrast (range 36-223 HU). Findings indicated that the CT visibility, characteristics of different abdominal lymph nodes may be variable in dogs.

Vertebral Osteosarcoma in Two Cats-Diagnosis, Treatment, and Outcome.

In this case report, we describe the diagnosis, treatment, and outcome of two feline cases of vertebral osteosarcoma. Case 1: A 6-year-old female neutered domestic longhaired cat was presented with progressive paraparesis, ataxia, and spinal hyperesthesia. MRI of the thoracolumbar spinal cord and vertebral column revealed a strongly contrast-enhancing mass lesion originating from the dorsal lamina and spinous process of T13. The lesion caused extradural compression of the spinal cord. Surgical debulking was performed, and the histopathological evaluation of surgical biopsies was consistent with vertebral osteosarcoma. The cat was paraplegic with intact nociception post-surgery. Subsequently, the cat recovered ambulation while remaining mildly ataxic and paraparetic at long-term follow-up. Post-operative chemotherapy was started with doxorubicin. CT scans at 2, 4, 9, 13, and 20 months post-surgery showed no signs of local recurrence or metastasis. Case 2: A 15.5-year-old male neutered domestic shorthaired cat was presented with progressive paraparesis, tail paresis, and spinal hyperesthesia. Radiographs and CT scan of the lumbar vertebral column showed a large mass originating from the dorsal lamina and spinous process of L6, suggestive of neoplasia, with severe compression of the spinal cord. Surgical debulking was performed, and the histopathological evaluation was consistent with vertebral osteosarcoma. Post-operative chemotherapy was started with doxorubicin. Seven months post-surgery, the patient was neurologically normal with no signs of metastatic disease. This case report highlights the possibility of good outcomes after the surgical treatment of feline vertebral osteosarcoma supplemented with post-surgical chemotherapy.

Epidemiology of Modic changes in dogs: Prevalence, possible risk factors, and association with spinal phenotypes.

Background: Chronic low back pain, a leading contributor to disease burden worldwide, is often caused by intervertebral disc (IVD) degeneration. Modic changes (MCs) are MRI signal intensity changes due to lesions in vertebral bone marrow adjacent to degenerated IVDs. Only a few studies described the histopathological changes associated with MC to date. MC type 1 is suggested to be associated with bone marrow infiltration of fibrovascular tissue, type 2 with fatty infiltration, and type 3 with bone sclerosis in humans. Methods: This study investigated whether the dog can be a valuable animal model to research MCs, by examining the prevalence, imaging, and histological characteristics of lumbar MCs in dogs (340 dogs, 2496 spinal segments). Results: Logistic regression analysis indicated that the presence of lumbosacral MCs was associated with age and disc herniation (annulus fibrosis protrusion and/or nucleus pulposus extrusion). According to MRI analysis, MCs were mostly detected at the lumbosacral junction in dogs. Most signal intensity changes represented MC type 3, while previous spinal surgery seemed to predispose for the development of MC type 1 and 2. Histological analysis (16 dogs, 39 spinal segments) indicated that IVDs with MCs showed more histopathological abnormalities in the endplate and vertebral bone marrow than IVDs without MCs. Mostly chondroid proliferation in the bone marrow was encountered, while the histologic anomalies described in humans associated with MCs, such as fibrovascular or fatty infiltration, were scarcely detected. Conclusions: Dogs spontaneously develop MCs, but may exhibit other pathological processes or more chronic bone marrow pathologies than humans with MCs. Therefore, more research is needed to determine the translatability of the MCs encountered in dog low-back-pain patients.

Hemophilia A Resulting in Severe Hyperesthesia Due to Extraparenchymal Spinal Cord Hemorrhage in a Young Golden Retriever Puppy.

A ten-week-old male Golden retriever puppy was presented with severe hyperesthesia, mild neurological deficits and episcleral bleeding. Clotting times showed a normal prothrombin time (PT) and prolonged activated partial thromboplastin time (aPPT). Computed tomography (CT) of the vertebral column showed intradural, extraparenchymal hyperattenuating changes on precontrast CT images and epidural mass lesions, suggestive of hematorrhachis. Hemophilia A was confirmed by a low-factor VIII activity (FVIII:C). Although the dog improved clinically with intravenous analgesia and cage rest, it was euthanized by the owners' choice because of the risk of developing future episodes of spontaneous hemorrhage. In young male puppies with severe hyperesthesia and mild neurological deficits, hemophilia A should be considered as a possible differential diagnosis.

Patient-specific 3D-printed shelf implant for the treatment of hip dysplasia tested in an experimental animal pilot in canines.

The concept of a novel patient-specific 3D-printed shelf implant should be evaluated in a relevant large animal model with hip dysplasia. Therefore, three dogs with radiographic bilateral hip dysplasia and a positive subluxation test underwent unilateral acetabular augmentation with a 3D-printed dog-specific titanium implant. The contralateral side served as control. The implants were designed on CT-based pelvic bone segmentations and extended the dysplastic acetabular rim to increase the weight bearing surface without impairing the range of motion. Outcome was assessed by clinical observation, manual subluxation testing, radiography, CT, and gait analysis from 6 weeks preoperatively until termination at 26 weeks postoperatively. Thereafter, all hip joints underwent histopathological examination. The implantation and recovery from surgery was uneventful. Clinical subluxation tests at the intervention side became negative. Imaging showed medialization of the femoral head at the intervention side and the mean (range) CE-angle increased from 94° (84°-99°) preoperative to 119° (117°-120°) postoperative. Gait analysis parameters returned to pre-operative levels after an average follow-up of 6 weeks. Histology showed a thickened synovial capsule between the implant and the femoral head without any evidence of additional damage to the articular cartilage compared to the control side. The surgical implantation of the 3D shelf was safe and feasible. The patient-specific 3D-printed shelf implants restored the femoral head coverage and stability of dysplastic hips without complications. The presented approach holds promise to treat residual hip dysplasia justifying future veterinary clinical trials to establish clinical effectiveness in a larger cohort to prepare for translation to human clinic.

Intra-Articular Slow-Release Triamcinolone Acetonide from Polyesteramide Microspheres as a Treatment for Osteoarthritis.

Osteoarthritis (OA) is a common cause of pain and disability. Local corticosteroid injections are effective in treating OA pain and inflammation but are short-acting. Prolonged intra-articular (IA) corticosteroid exposure may even lead to cartilage deterioration. The aim of this prospective study was to assess safety and provide proof-of-concept of IA-applied biodegradable polyesteramide-based microspheres (PEAMs) gradually releasing triamcinolone acetonide (TA). Mimicking continuous exposure associated with local drug delivery in canine articular chondrocytes cultured in the continuous presence of TA tissue regeneration was not affected, whereas intermittent exposure reduced proteoglycan production. In this respect, TA-PEAMs administered IA in a proof-of-concept study in 12 client-owned dogs with established OA also showed safety by radiographic examination, without changes in OA severity and in glycosaminoglycan synovial fluid levels. Treatment also resulted in clinical improvement in 10 out of 11 dogs during the two-month follow-up period, which persisted in 6 out of 10 dogs after 6 months, based on objective gait analysis and owner questionnaires. Synovial prostaglandin E2, a pro-inflammatory marker, was decreased two months after treatment. This study showed safety and proof-of-concept of IA-administered TA-PEAMs in dogs with OA, as a first step towards translation into the veterinary and human clinic.

Prospective Evaluation of Local Sustained Release of Celecoxib in Dogs with Low Back Pain.

Back pain affects millions globally and in 40% of the cases is attributed to intervertebral disc degeneration. Oral analgesics are associated with adverse systemic side-effects and insufficient pain relief. Local drug delivery mitigates systemic effects and accomplishes higher local dosing. Clinical efficacy of intradiscally injected celecoxib (CXB)-loaded polyesteramide microspheres (PEAMs) was studied in a randomized prospective double-blinded placebo controlled veterinary study. Client-owned dog patients suffering from back pain were treated with CXB-loaded (n = 20) or unloaded PEAMs ("placebo") (n = 10) and evaluated by clinical examination, gait analysis, owners' questionnaires, and MRI at 6 and 12 weeks follow-up. At 6 and 12 weeks, CXB-treated dogs experienced significantly less pain interference with their daily life activities compared to placebo. The risk ratio for treatment success was 1.90 (95% C.I. 1.24-2.91, p = 0.023) at week 6 and 1.95 (95% C.I. 1.10-3.45, p = 0.036) at week 12. The beneficial effects of CXB-PEAMs were more pronounced for the subpopulation of male dogs and those with no Modic changes in MRI at inclusion in the study; disc protrusion did not affect the outcome. It remains to be determined whether intradiscal injection of CXB-PEAMs, in addition to analgesic properties, has the ability to halt the degenerative process in the long term or restore the disc.

Structural, compositional, and functional effects of blunt and sharp cartilage damage on the joint: A 9-month equine groove model study.

This study aimed to quantify the long-term progression of blunt and sharp cartilage defects and their effect on joint homeostasis and function of the equine carpus. In nine adult Shetland ponies, the cartilage in the radiocarpal and middle carpal joint of one front limb was grooved (blunt or sharp randomized). The ponies were subjected to an 8-week exercise protocol and euthanized at 39 weeks. Structural and compositional alterations in joint tissues were evaluated in vivo using serial radiographs, synovial biopsies, and synovial fluid samples. Joint function was monitored by quantitative gait analysis. Macroscopic, microscopic, and biomechanical evaluation of the cartilage and assessment of subchondral bone parameters were performed ex vivo. Grooved cartilage showed higher OARSI microscopy scores than the contra-lateral sham-operated controls (p < 0.0001). Blunt-grooved cartilage scored higher than sharp-grooved cartilage (p = 0.007) and fixed charge density around these grooves was lower (p = 0.006). Equilibrium and instantaneous moduli trended lower in grooved cartilage than their controls (significant for radiocarpal joints). Changes in other tissues included a threefold to sevenfold change in interleukin-6 expression in synovium from grooved joints at week 23 (p = 0.042) and an increased CPII/C2C ratio in synovial fluid extracted from blunt-grooved joints at week 35 (p = 0.010). Gait analysis outcome revealed mild, gradually increasing lameness. In conclusion, blunt and, to a lesser extent, sharp grooves in combination with a period of moderate exercise, lead to mild degeneration in equine carpal cartilage over a 9-month period, but the effect on overall joint health remains limited.

Safety of intradiscal delivery of triamcinolone acetonide by a poly(esteramide) microsphere platform in a large animal model of intervertebral disc degeneration.

BACKGROUND CONTEXT: Local corticosteroids have been used to relieve symptoms of chronic low back pain, although treatment effects have been shown to wear off relatively fast. Prolonging corticosteroid presence by controlled release from biomaterials may allow for longer pain relief while circumventing adverse effects such as high bolus dosages. PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intradiscal controlled release of triamcinolone acetonide (TAA) by poly(esteramide) microspheres in a canine degenerated intervertebral disc (IVD) model. STUDY DESIGN: In a preclinical experimental large animal model, the effect of prolonged glucocorticoid exposure on disc degeneration was evaluated. METHODS: Degeneration was accelerated by nucleotomy of lumbar IVDs of Beagle dogs. After 4 weeks, microspheres loaded with 8.4 µg TAA, and 0.84mg TAA were administered to the degenerated IVDs by intradiscal injection (n=6 per group). Empty microspheres (n=6) and all adjacent non-nucleotomized noninjected IVDs were included as controls (n=24). Immediately prior to TAA administration and after 12 weeks, magnetic resonance imaging was performed. Degenerative changes were evaluated by disc height index, Pfirrmann grading, T1ρ and T2 mapping values, postmortem CT scans, macroscopic and microscopic grading, and biochemical/immunohistochemical analysis of inflammation and extracellular matrix content. In addition, nerve growth factor (NGF) protein expression, a biomarker for pain, was scored in nucleus pulposus (NP) tissues. The study was funded by a research grant from Health Holland (1.3million euros = 1.5million US dollars). RESULTS: Macroscopic evaluation and CT images postmortem were consistent with mild disc degeneration. Other abnormalities were not observed. Nucleotomy-induced degeneration and inflammation was mild, reflected by moderate Pfirrmann grades and PGE2 levels. Regardless of TAA dosage, local sustained delivery did not affect disc height index nor Pfirrmann grading, T1ρ and T2 mapping values, PGE2 tissue levels, collagen, GAG, and DNA content. However, the low dosage of TAA microspheres significantly reduced NGF immunopositivity in degenerated NP tissue. CONCLUSIONS: This is the first in vivo application in a preclinical large animal model of a controlled release formulation of corticosteroids in mild IVD degeneration. Sustained release of TAA locally in the IVD appeared safe and reduced NGF expression, suggesting its potential applicability for pain relief, although beneficial effects were absent on tissue degeneration. CLINICAL SIGNIFICANCE: The present platform seems to be promising in extending the local controlled delivery of TAA with the potency to provide long-standing analgesia in the subset of LBP patients suffering from discogenic pain.

Caudal lumbar spinal cysts in two French Bulldogs.

BACKGROUND: Spinal cysts are rare findings in veterinary medicine, but they are increasingly recognized due to the availability of advanced imaging techniques. Extradural meningeal cysts in French Bulldogs have not been reported previously and arachnoid cysts (diverticula) have not been reported at the caudal lumbar (L6-L7) region in dogs. CASE PRESENTATION: Two French Bulldogs, aged 5 and 8 years, were referred for evaluation of lower back pain and bilateral hind limb neurological deficits. Neurologic examination revealed ataxia and postural deficits in both dogs. Magnetic resonance imaging (MRI) showed cauda equina compression due to a cyst-like lesion at the level of L6-L7 in both cases. The dogs underwent dorsal laminectomy and the meningeal cyst was completely removed in one dog and in the other dog the spinal arachnoid diverticula was marsupialized. In Case 1, histopathology of the cysts was performed and MRI was repeated. Both dogs were pain free during follow-up evaluations. CONCLUSIONS: Based on radiological, intra-operative and histopathological findings, the first case was diagnosed as a meningocele connected by a pedicle to the caudal tip of the dural sac forming a dural diverticulum categorized as an extradural spinal cyst type Ib, and Case 2 as a type III intradural arachnoid diverticula. It is concluded that spinal cysts should be included in the differential diagnosis of cauda equina syndrome and lower back pain in French Bulldogs. Results of these cases may be useful for diagnostic and treatment management.

Temporary Segmental Distraction in a Dog with Degenerative Lumbosacral Stenosis.

OBJECTIVES: Degenerative lumbosacral stenosis (DLSS) is characterized by intervertebral disc degeneration and causes lower back pain in dogs. Temporary distraction in rabbit models with induced intervertebral disc degeneration showed signs of intervertebral disc repair. In the present study, we assessed safety and efficacy of temporary segmental distraction in a dog with clinical signs of DLSS. METHODS: Distraction of the lumbosacral junction by pedicle screw-rod fixation was applied in a 5-year-old Greyhound with DLSS and evaluated by radiography, magnetic resonance imaging, and force plate analysis before and after distraction. RESULTS: Safe distraction of the lumbosacral junction was demonstrated, with improvement of clinical signs after removal of the distraction device. Signal intensity of the intervertebral disc showed no changes over time. T2 value was highest directly after removal of the distraction device but decreased by 10% of the preoperative value at 9 months of follow-up. Disc height decreased (8%) immediately after removal of the distraction device, but recovered to the initial value. A decrease in the pelvic/thoracic propulsive force during pedicle screw-rod fixation and distraction was demonstrated, which slowly increased by 4% compared with the initial value. CLINICAL SIGNIFICANCE: Temporary pedicle screw-rod fixation in combination with distraction in a dog with DLSS was safe, improved clinical signs and retained disc height at 9 months of follow-up.

Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix: from bench towards bedside.

The socioeconomic burden of chronic back pain related to intervertebral disc (IVD) disease is high and current treatments are only symptomatic. Minimally invasive strategies that promote biological IVD repair should address this unmet need. Notochordal cells (NCs) are replaced by chondrocyte-like cells (CLCs) during IVD maturation and degeneration. The regenerative potential of NC-secreted substances on CLCs and mesenchymal stromal cells (MSCs) has already been demonstrated. However, identification of these substances remains elusive. Innovatively, this study exploits the regenerative NC potential by using healthy porcine NC-derived matrix (NCM) and employs the dog as a clinically relevant translational model. NCM increased the glycosaminoglycan and DNA content of human and canine CLC aggregates and facilitated chondrogenic differentiation of canine MSCs in vitro. Based on these results, NCM, MSCs and NCM+MSCs were injected in mildly (spontaneously) and moderately (induced) degenerated canine IVDs in vivo and, after six months of treatment, were analyzed. NCM injected in moderately (induced) degenerated canine IVDs exerted beneficial effects at the macroscopic and MRI level, induced collagen type II-rich extracellular matrix production, improved the disc height, and ameliorated local inflammation. MSCs exerted no (additive) effects. In conclusion, NCM induced in vivo regenerative effects on degenerated canine IVDs. NCM may, comparable to demineralized bone matrix in bone regeneration, serve as 'instructive matrix', by locally releasing growth factors and facilitating tissue repair. Therefore, intradiscal NCM injection could be a promising regenerative treatment for IVD disease, circumventing the cumbersome identification of bioactive NC-secreted substances.

Intradiscal application of a PCLA-PEG-PCLA hydrogel loaded with celecoxib for the treatment of back pain in canines: What's in it for humans?

Chronic low back pain is a common clinical problem in both the human and canine population. Current pharmaceutical treatment often consists of oral anti-inflammatory drugs to alleviate pain. Novel treatments for degenerative disc disease focus on local application of sustained released drug formulations. The aim of this study was to determine safety and feasibility of intradiscal application of a poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-bpoly(ε-caprolactone-co-lactide) PCLA-PEG-PCLA hydrogel releasing celecoxib, a COX-2 inhibitor. Biocompatibility was evaluated after subcutaneous injection in mice, and safety of intradiscal injection of the hydrogel was evaluated in experimental dogs with early spontaneous intervertebral disc (IVD) degeneration. COX-2 expression was increased in IVD samples surgically obtained from canine patients, indicating a role of COX-2 in clinical IVD disease. Ten client-owned dogs with chronic low back pain related to IVD degeneration received an intradiscal injection with the celecoxib-loaded hydrogel. None of the dogs showed adverse reactions after intradiscal injection. The hydrogel did not influence magnetic resonance imaging signal at long-term follow-up. Clinical improvement was achieved by reduction of back pain in 9 of 10 dogs, as was shown by clinical examination and owner questionnaires. In 3 of 10 dogs, back pain recurred after 3 months. This study showed the safety and effectiveness of intradiscal injections in vivo with a thermoresponsive PCLA-PEG-PCLA hydrogel loaded with celecoxib. In this set-up, the dog can be used as a model for the development of novel treatment modalities in both canine and human patients with chronic low back pain.