Pathogenic variants in COL6A3 cause Ullrich-like congenital muscular dystrophy in young Labrador Retriever dogs.

The collagen VI-related muscular dystrophies in people include a broad spectrum of diseases ranging from the severe Ullrich congenital muscular dystrophy to the mild Bethlem myopathy. Clinical features are attributable to both muscle and connective tissue and include progressive muscle weakness and respiratory failure, hyperlaxity of distal joints, and progressive contracture of large joints. Here we describe two different COL6A3 pathogenic variants in Labrador Retriever dogs that result in autosomal recessive or autosomal dominant congenital myopathies with hyperlaxity of distal joints and joint contracture, similar to the condition in people.

Biomechanical Comparison of Three Crural Fascia Repair Techniques for Tibial Tuberosity Advancement Surgery.

OBJECTIVES: The aim of this study was to compare the strength of three described techniques for repair of the medial crural fascia to the strength of the intact fascia of the paired limbs. We hypothesized that intact controls would have higher peak loads at failure than repair groups and that the modified Mason-Allen suture pattern would have the highest peak load at failure of the repair groups. MATERIALS AND METHODS: Canine cadavers (n = 22) were randomly assorted into three groups. Group A: a continuous suture pattern. Group B: five equally spaced simple interrupted cruciate sutures over a simple continuous suture pattern. Group C: an interrupted modified Mason-Allen suture pattern. The mid-portion of the crural fascia was incised in Groups A and C, while Group B used a cranial incision. Contralateral limbs were utilized as paired controls. Tibiae were mounted to a biomaterial testing machine and the medial crural fascia loaded at 10 mm/min. RESULTS: Mean peak load to failure for Group A: 201.0N, Group B: 261.0N, Group C: 306.1N and Intact limbs: 799.5N. Between repair groups, there was no significant difference between peak loads to failure identified. Significant differences were identified between all repairs and intact limbs. All repairs approached a mean of 33.5% (267.8N) of intact medial crural fascia strength. CLINICAL SIGNIFICANCE: All repair techniques met no more than 1/3 intact medial crural fascia strength. Further research is required to continue to evaluate the most clinically appropriate technique to repair the medial tibial crural fascia.

Stiffness Matters: Part II-The Effects of Plate Stiffness on Load-Sharing and the Progression of Fusion Following Anterior Cervical Discectomy and Fusion In Vivo.

STUDY DESIGN: Real time in vivo measurement of forces in the cervical spine of goats following anterior cervical discectomy and fusion (ACDF). OBJECTIVE: To measure interbody forces in the cervical spine during the time course of fusion following ACDF with plates of different stiffnesses. SUMMARY OF BACKGROUND DATA: Following ACDF, the biomechanics of the arthrodesis is largely dictated by the plate. The properties of the plate prescribe the extent of load-sharing through the disc space versus the extent of stress-shielding. Load-sharing promotes interbody bone formation and stress-shielding can inhibit maturation of bone. However, these principles have never been validated in vivo. Measuring in vivo biomechanics of the cervical spine is critical to understanding the complex relationships between implant design, interbody loading, load-sharing, and the progression of fusion. METHODS: Anterior cervical plates of distinct bending stiffnesses were placed surgically following ACDF in goats. A validated custom force-sensing interbody implant was placed in the disc space to measure load-sharing in the spine. Interbody loads were measured in vivo in real time during the course of fusion for each plate. RESULTS: Interbody forces during flexion/extension were highly dynamic. In animals that received high stiffness plates, maximum forces were in extension whereas in animals that received lower stiffness plates, maximum forces were in flexion. As fusion progressed, interbody load magnitude decreased. CONCLUSION: The magnitude of interbody forces in the cervical spine is dynamic and correlates to activity and posture of the head and neck. The magnitude and consistency of forces in the interbody space correlates to plate stiffness with more compliant plates resulting in more consistent load-sharing. The magnitude of interbody forces decreases as fusion matures suggesting that smart interbody implants may be used as a diagnostic tool to indicate the progression of interbody fusion. LEVEL OF EVIDENCE: N/A.

Load-sharing through elastic micro-motion accelerates bone formation and interbody fusion.

BACKGROUND CONTEXT: Achieving a successful spinal fusion requires the proper biological and biomechanical environment. Optimizing load-sharing in the interbody space can enhance bone formation. For anterior cervical discectomy and fusion (ACDF), loading and motion are largely dictated by the stiffness of the plate, which can facilitate a balance between stability and load-sharing. The advantages of load-sharing may be substantial for patients with comorbidities and in multilevel procedures where pseudarthrosis rates are significant. PURPOSE: We aimed to evaluate the efficacy of a novel elastically deformable, continuously load-sharing anterior cervical spinal plate for promotion of bone formation and interbody fusion relative to a translationally dynamic plate. STUDY DESIGN/SETTING: An in vivo animal model was used to evaluate the effects of an elastically deformable spinal plate on bone formation and spine fusion. METHODS: Fourteen goats underwent an ACDF and received either a translationally dynamic or elastically deformable plate. Animals were followed up until 18 weeks and were evaluated by plain x-ray, computed tomography scan, and undecalcified histology to evaluate the rate and quality of bone formation and interbody fusion. RESULTS: Animals treated with the elastically deformable plate demonstrated statistically significantly superior early bone formation relative to the translationally dynamic plate. Trends in the data from 8 to 18 weeks postoperatively suggest that the elastically deformable implant enhanced bony bridging and fusion, but these enhancements were not statistically significant. CONCLUSIONS: Load-sharing through elastic micro-motion accelerates bone formation in the challenging goat ACDF model. The elastically deformable implant used in this study may promote early bony bridging and increased rates of fusion, but future studies will be necessary to comprehensively characterize the advantages of load-sharing through micro-motion.

ISSLS Prize Winner: Dynamic Loading-Induced Convective Transport Enhances Intervertebral Disc Nutrition.

STUDY DESIGN: Experimental animal study of convective transport in the intervertebral disc. OBJECTIVE: To quantify the effects of mechanical loading rate on net transport into the healthy and degenerative intervertebral disc in vivo. SUMMARY OF BACKGROUND DATA: Intervertebral disc degeneration is linked with a reduction in transport to the avascular disc. Enhancing disc nutrition is, therefore, a potential strategy to slow or reverse the degenerative cascade. Convection induced by mechanical loading is a potential mechanism to augment diffusion of small molecules into the disc. METHODS: Skeletally mature New Zealand white rabbits with healthy discs and discs degenerated via needle puncture were subjected to low rate axial compression and distraction loading for 2.5, 5, 10, 15, or 20 minutes after a bolus administration of gadodiamide. Additional animals with healthy discs were subjected to high-rate loading for 10 minutes or no loading for 10 minutes. Transport into the disc for each loading regimen was quantified using post-contrast-enhanced magnetic resonance imaging. RESULTS: Low-rate loading resulted in the rapid uptake and clearance of gadodiamide in the disc. Low-rate loading increased net transport into the nucleus by a mean 16.8% and 12.6% in healthy and degenerative discs, respectively. The kinetics of small molecule uptake and clearance were accelerated in both healthy and degenerative discs with low-rate loading. In contrast, high-rate loading reduced transport into nucleus by a mean 16.8%. CONCLUSION: These results illustrate that trans-endplate diffusion can be enhanced by forced convection in both healthy and degenerative discs in vivo. Mechanical loading-induced convection could offer therapeutic benefit for degenerated discs by enhancing uptake of nutrients and clearance of by-products. LEVEL OF EVIDENCE: 4.

Low rate loading-induced convection enhances net transport into the intervertebral disc in vivo.

BACKGROUND CONTEXT: The intervertebral disc primarily relies on trans-endplate diffusion for the uptake of nutrients and the clearance of byproducts. In degenerative discs, diffusion is often diminished by endplate sclerosis and reduced proteoglycan content. Mechanical loading-induced convection has the potential to augment diffusion and enhance net transport into the disc. The ability of convection to augment disc transport is controversial and has not been demonstrated in vivo. PURPOSE: To determine if loading-induced convection can enhance small molecule transport into the intervertebral disc in vivo. STUDY DESIGN: Net transport was quantified via postcontrast enhanced magnetic resonance imaging (MRI) into the discs of the New Zealand white rabbit lumbar spine subjected to in vivo cyclic low rate loading. METHODS: Animals were administered the MRI contrast agent gadodiamide intravenously and subjected to in vivo low rate loading (0.5 Hz, 200 N) via a custom external loading apparatus for either 2.5, 5, 10, 15, or 20 minutes. Animals were then euthanized and the lumbar spines imaged using postcontrast enhanced MRI. The T1 constants in the nucleus, annulus, and cartilage endplates were quantified as a measure of gadodiamide transport into the loaded discs compared with the adjacent unloaded discs. Microcomputed tomography was used to quantify subchondral bone density. RESULTS: Low rate loading caused the rapid uptake and clearance of gadodiamide in the nucleus compared with unloaded discs, which exhibited a slower rate of uptake. Relative to unloaded discs, low rate loading caused a maximum increase in transport into the nucleus of 16.8% after 5 minutes of loading. Low rate loading increased the concentration of gadodiamide in the cartilage endplates at each time point compared with unloaded levels. CONCLUSIONS: Results from this study indicate that forced convection accelerated small molecule uptake and clearance in the disc induced by low rate mechanical loading. Low rate loading may, therefore, be therapeutic to the disc as it may enhance the nutrient uptake and waste product clearance.

Small intestinal submucosa for anular defect closure: long-term response in an in vivo sheep model.

STUDY DESIGN: After undergoing anulotomy, lumbar intervertebral discs from sheep were treated with small intestinal submucosa (SIS) and assessed functionally at 24 weeks after surgery. OBJECTIVE: To determine the efficacy of an SIS-based patch and plug scaffold to facilitate anular defect closure and anular functional recovery after anulotomy and partial discectomy. SUMMARY OF BACKGROUND DATA: The incidence of reherniation following discectomy remains high and mechanical means of anular closure have met with limited success. SIS is a naturally occurring collagen-based material, which acts as a resorbable scaffold in vivo that promotes soft tissue regeneration. METHODS: Twelve sheep underwent retroperitoneal exposure of the lumbar spine. Three levels were assigned to either: no additional procedure, box anulotomy alone, or box anulotomy followed by placement of an SIS "patch and plug" anchored by titanium bone screws. At 26 weeks after surgery, 18 motion segments underwent pressure-volume testing to assess the competency of the anulus. High resolution MRI images were taken of the remaining 18 segments. Undecalcified histology was conducted on all specimens. RESULTS: Radiographs, MRI images, and histology indicate that there was an exuberant tissue response at SIS-treated levels. New tissue formation in SIS-treated specimens was integrated well with the native anulus, but did not resemble the organization of native anulus. The extent of anular closure was substantial enough to allow the disc a functional recovery to a mean 66% of its capacity to develop internal pressure. MRI images indicate that SIS-treated levels did not maintain signal intensity comparable to exposure-only (intact) levels, but SIS-treated discs were statistically significantly higher than anulotomy-only levels. CONCLUSION: SIS-treated discs were better able to maintain hydration and resulted in a functional recovery relative to anulotomy alone levels. The SIS patch and plug reduced the cascade of functional degeneration that an intervertebral disc undergoes following anulotomy.