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Regeneration of hyaline cartilage in human-sized joints remains a clinical challenge, and it is a critical unmet need that would contribute to longer healthspans. Injectable scaffolds for cartilage repair that integrate both bioactivity and sufficiently robust physical properties to withstand joint stresses offer a promising strategy. We report here on a hybrid biomaterial that combines a bioactive peptide amphiphile supramolecular polymer that specifically binds the chondrogenic cytokine transforming growth factor ß-1 (TGFß-1) and crosslinked hyaluronic acid microgels that drive formation of filament bundles, a hierarchical motif common in natural musculoskeletal tissues. The scaffold is an injectable slurry that generates a porous rubbery material when exposed to calcium ions once placed in cartilage defects. The hybrid material was found to support in vitro chondrogenic differentiation of encapsulated stem cells in response to sustained delivery of TGFß-1. Using a sheep model, we implanted the scaffold in shallow osteochondral defects and found it can remain localized in mechanically active joints. Evaluation of resected joints showed significantly improved repair of hyaline cartilage in osteochondral defects injected with the scaffold relative to defects injected with the growth factor alone, including implantation in the load-bearing femoral condyle. These results demonstrate the potential of the hybrid biomimetic scaffold as a niche to favor cartilage repair in mechanically active joints using a clinically relevant large-animal model. [ABSTRACT FROM AUTHOR]

Sieve electrodes stand poised to deliver the selectivity required for driving advanced prosthetics but are considered inherently invasive and lack the stability required for a chronic solution. This proof of concept experiment investigates the potential for the housing and engagement of a sieve electrode within the medullary canal as part of an osseointegrated neural interface (ONI) for greater selectivity toward improving prosthetic control. The working hypotheses are that (A) the addition of a sieve interface to a cuff electrode housed within the medullary canal of the femur as part of an ONI would be capable of measuring efferent and afferent compound nerve action potentials (CNAPs) through a greater number of channels; (B) that signaling improves over time; and (C) that stimulation at this interface generates measurable cortical somatosensory evoked potentials through a greater number of channels. The modified ONI was tested in a rabbit (n = 1) amputation model over 12 weeks, comparing the sieve component to the cuff, and subsequently compared to historical data. Efferent CNAPs were successfully recorded from the sieve demonstrating physiological improvements in CNAPs between weeks 3 and 5, and somatosensory cortical responses recorded at 12 weeks postoperatively. This demonstrates that sieve electrodes can be housed and function within the medullary canal, demonstrated by improved nerve engagement and distinct cortical sensory feedback. This data presents the conceptual framework for housing more sophisticated sieve electrodes in bone as part of an ONI for improving selectivity with percutaneous connectivity toward improved prosthetic control. [ABSTRACT FROM AUTHOR]

Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined. In vitro studies suggest involvement of intracellular signaling through mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and mammalian target of rapamycin (mTOR). However, anabolic signaling responses to bone loading using a whole animal in vivo model have not been studied in detail. Therefore, we examined mechanically-induced signaling events at five time points from 0 to 24 hours after loading using the rat in vivo ulna end-loading model. Western blot analysis of bone for MAPK’s, PI3K/Akt, and mTOR signaling, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to estimate gene expression of calcitonin gene-related protein alpha (CGRP-α), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), c-jun, and c-fos in dorsal root ganglion (DRG) of the brachial intumescence were performed. There was a significant increase in signaling through MAPK’s including extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) in loaded limbs at 15 minutes after mechanical loading. Ulna loading did not significantly influence expression of the genes of interest in DRG neurons. Bone signaling and DRG gene expression from the loaded and contralateral limbs was correlated (SR>0.40, P<0.05). However, bone signaling did not correlate with expression of the genes of interest in DRG neurons. These results suggest that signaling through the MAPK pathway may be involved in load-induced bone formation in vivo. Further characterization of the molecular events involved in regulation of bone adaptation is needed to understand the timing and impact of loading events, and the contribution of the neuronal signaling to functional adaptation of bone. [ABSTRACT FROM AUTHOR]

Articular stress fracture arising from the distal end of the third metacarpal bone (MC3) is a common serious injury in Thoroughbred racehorses. Currently, there is no method for predicting fracture risk clinically. We describe an ex-vivo biomechanical model in which we measured subchondral crack micromotion under compressive loading that modeled high speed running. Using this model, we determined the relationship between subchondral crack dimensions measured using computed tomography (CT) and crack micromotion. Thoracic limbs from 40 Thoroughbred racehorses that had sustained a catastrophic injury were studied. Limbs were radiographed and examined using CT. Parasagittal subchondral fatigue crack dimensions were measured on CT images using image analysis software. MC3 bones with fatigue cracks were tested using five cycles of compressive loading at -7,500N (38 condyles, 18 horses). Crack motion was recorded using an extensometer. Mechanical testing was validated using bones with 3 mm and 5 mm deep parasagittal subchondral slots that modeled naturally occurring fatigue cracks. After testing, subchondral crack density was determined histologically. Creation of parasagittal subchondral slots induced significant micromotion during loading (p<0.001). In our biomechanical model, we found a significant positive correlation between extensometer micromotion and parasagittal crack area derived from reconstructed CT images (SR = 0.32, p<0.05). Correlations with transverse and frontal plane crack lengths were not significant. Histologic fatigue damage was not significantly correlated with crack dimensions determined by CT or extensometer micromotion. Bones with parasagittal crack area measurements above 30 mm2 may have a high risk of crack propagation and condylar fracture in vivo because of crack micromotion. In conclusion, our results suggest that CT could be used to quantify subchondral fatigue crack dimensions in racing Thoroughbred horses in-vivo to assess risk of condylar fracture. Horses with parasagittal crack arrays that exceed 30 mm2 may have a high risk for development of condylar fracture. [ABSTRACT FROM AUTHOR]

ABSTRACT Experimental studies have shown the ability of statins to stimulate bone formation when delivered locally or in large oral doses, however most have been studied in rodents. This anabolic effect is through the selective activation of BMP-2. Our purpose was to determine the effects of local treatment with lovastatin on bone healing in mammals as a preclinical animal model. We administered lovastatin (6 mg/kg) by percutaneous injection to a canine tibial osteotomy stabilized with external fixation. We found that lovastatin improved bone healing after a single injection into the fracture site assessed by serial radiography and histology at bone union. However, lovastatin treatment resulted in adverse local soft tissue inflammation. These results suggest that percutaneous lovastatin injection may be a useful adjuvant treatment over the course of bone healing to augment fracture repair, although further investigation into the mechanism of soft tissue adverse effects is warranted. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:210-216, 2014. [ABSTRACT FROM AUTHOR]

Despite the potential for growth factor delivery strategies to promote orthopedic implant healing, there is a need for growth factor delivery methods that are controllable and amenable to clinical translation. We have developed a modular bone growth factor, herein termed "modular bone morphogenetic peptide (mBMP)", which was designed to efficiently bind to the surface of orthopedic implants and also stimulate new bone formation. The purpose of this study was to coat a hydroxyapatite-titanium implant with mBMP and evaluate bone healing across a bone-implant gap in the sheep femoral condyle. The mBMP molecules efficiently bound to a hydroxyapatite-titanium implant and 64% of the initially bound mBMP molecules were released in a sustained manner over 28 days. The results demonstrated that the mBMP-coated implant group had significantly more mineralized bone filling in the implant-bone gap than the control group in C-arm computed tomography (DynaCT) scanning (25% more), histological (35% more) and microradiographic images (50% more). Push-out stiffness of the mBMP group was nearly 40% greater than that of control group whereas peak force did not show a significant difference. The results of this study demonstrated that mBMP coated on a hydroxyapatite-titanium implant stimulates new bone formation and may be useful to improve implant fixation in total joint arthroplasty applications. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the effects of loading of a single bone on adaptation of other appendicular long bones and if these responses were neuronally regulated. It is inferred that functional skeletal adaptation is controlled by osteocytes, but can also be regulated by the nervous system. The study employed young male Sprague-Dawley rats. To induce a modeling response, the right ulna of the rats was loaded. It is concluded that increased bone formation in multiple bones was induced by ulna loading, in growing, young male rats.

This study was to determine the efficacy of recombinant human bone morphogenetic protien-2 (rhBMP-2)/calcium phosphate matrix (CPX) paste to accelerate healing in a canine articular fracture model with associated subchondral defect. rhBMP-2/CPX (BMP), CPX alone (CPX) or autogenous bone graft (ABG) was administered to a canine articular tibial plateau osteotomy with a subchondral defect in each of 21 female dogs. The unoperated contralateral limbs served as controls. Ground reaction forces, synovial fluid, radiographic changes, mechanical testing, bone density, and histology of bone and synovium were analyzed at 6 weeks after surgery. Radiographic analysis demonstrated that the BMP and CPX groups showed improved bony healing compared to the ABG group at week 6. Histomorphometric analysis demonstrated that the BMP group had significantly increased trabecular bone volume compared to the CPX and ABG groups. Mechanical testing revealed that the BMP group had significantly greater maximum failure loads than the ABG group. Histological analysis demonstrated that the BMP group had significantly less sub-synovial inflammation than CPX group. This study demonstrated that rhBMP-2/CPX accelerated healing of articular fractures with subchondral defect compared to ABG in most of the parameters evaluated, and had less subsynovial inflammation than the CPX alone in a canine model. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 466-471, 2009 [ABSTRACT FROM AUTHOR]

Background: The double-bundle technique has recently gained much interest in ligament reconstruction. In addition to potential kinematic advantages, perhaps double tunnels have the potential for faster and more secure tendon-to-bone healing. Hypothesis: Placement of tendons in 2 osseous tunnels, as opposed to 1, will enhance tendon fixation as determined biomechanically and histologically. Study Design: Controlled laboratory study. Methods: Fourteen sheep were used, and an extra-articular tendon graft reconstruction was performed on both knees of each sheep. In 1 randomly selected knee, the long digital extensor tendon was released from the femur and placed into a single tunnel in the proximal tibia. In the contralateral knee, the tendon was split and placed into 2 tibial tunnels. Ten sheep were analyzed by mechanical testing, and the remaining 4 were subjected to histologic evaluation at 6 weeks after surgery. Paired t tests were used for statistical analysis. Results: Mechanical testing demonstrated that the peak load (981.8 ± 143.2 N, mean ± SD) and stiffness (570.9 ± 114.6 N/mm) at 6 weeks after surgery in the double-tunnel group were significantly greater than for the single-tunnel group (714.8 ± 94.2 N and 432.2 ± 56.7 N/mm, respectively; load, P = .007; stiffness, P = .03). Histologic analysis suggested similar tendon-to-bone healing for both groups. Conclusion: This study demonstrated enhanced biomechanical fixation of the tendon to the surrounding bone in the doubletunnel compared with the single-tunnel technique in this ovine model. Clinical Relevance: The double-tunnel technique may provide better fixation and healing in human ligament reconstruction. [ABSTRACT FROM AUTHOR]

In this 18 month in vivo canine study we compared three methods of attaching the gluteal muscles to the proximal femur during hip reconstruction with an allograft-prosthesis composite (APC). All three methods are commonly practiced in human hip revision surgery and data on their effectiveness in dogs is directly relevant to human treatment. The methods compared were host gluteal tendon sutured to allograft tendon, host greater trochanter apposed to allograft using a cable grip system, and host cortical bone shells around the allograft secured with cerclage wires. For each method, we assessed changes in allograft-host bone fusion, weight bearing, gluteal muscle mass, and structural properties through qualitative radiography, gait analysis, histology, and biomechanical testing. Hip reconstruction using the WRAP method resulted in the greatest limb use with complete resolution of gluteal muscle atrophy 18 months after surgery. This method yielded a stronger, more stable hip joint that allowed for more normal limb function. These hips had the more rapid rate of bony union at the host bone-allograft junction and little resorption of the graft. The increased limb use and resultant larger gluteal muscle mass conferred to the WRAP hip composites the greatest tensile strength and stiffness when tested 18 months after reconstruction. There was a large amount of new bone formation on the periosteal surface where the WRAP reconstructions had an overlay of live bone that resulted in a more rapid union and increased cortical width at the level of the osteotomy. New bone also penetrated into the allograft a greater distance from the osteotomy in the WRAP group. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:208-220, 2007 [ABSTRACT FROM AUTHOR]

Objectives To evaluate the effects of intra-articular protection (IAP) on the canine cranial cruciate ligament (CrCL) and stifle in a CrCL midsubstance elongation injury model. Study Design Experimental longitudinal cohort study. Animals Skeletally mature female mixed breed hounds (n=12; mean±SEM weight, 25.6±0.7 kg). Methods After CrCL elongation in 1 stifle of each dog, IAP was applied in 6 joints. In vivo assessment included radiographs, cranial–caudal joint translation, gait analysis, and synovial fluid levels of 3B3(−) (proteoglycan epitope) and C2C (collagen II neoepitope) up to 12 weeks after surgery. Joint translation and rotation were quantified at necropsy. CrCL midsubstance length was determined before and after elongation and at necropsy. CrCLs were subjectively assessed with light microscopy. Comparisons were made between stifles containing elongated CrCLs with and without IAP and unoperated controls. Results Four weeks after surgery, ground reaction forces were significantly decreased in operated limbs. Absolute C2C levels were significantly elevated in operated stifles 4 weeks post-surgery. C2C and 3B3(−) levels normalized to total protein were significantly elevated in IAP+ stifles 8 weeks after surgery. Protected CrCLs appeared to have decreased granulation tissue and better collagen fiber alignment. Conclusions IAP has negligible effects on the canine stifle based on the response variables evaluated in this 12-week study. Protection of elongated CrCLs may promote reduced, organized scar formation. Clinical Relevance These results support the healing capacity of the canine CrCL midsubstance following elongation injury and IAP application to potentially reduce cicatrix formation in elongated CrCLs. [ABSTRACT FROM AUTHOR]

Objective To compare the orthogonal radiographic (OR) and computed tomographic (CT) appearance of paired Thoroughbred racehorse limbs with severe condylar fracture. Study Design In vitro study. Sample Population Cadaveric paired limbs with severe condylar fracture (n=11 horses). Methods Four standard radiographic and multiple transverse CT images were obtained of the fractured and contralateral limbs centering on the metacarpo/metatarsophalangeal (fetlock) joints. Radiographs and CT images were graded by 4 raters, and interobserver agreement was calculated. Imaging evaluations were supplemented by fetlock joint dissection. A consensus description of actual injury and the detection accuracy of OR and CT for that injury was determined. Results Rater agreement for OR and CT for most pathologic features was good or excellent. OR was similar to CT for the detection of condylar and diaphyseal third metacarpal and metatarsal (MC/MT3) fractures, diaphyseal fractures of the first phalanx (P1), and fracture location on the condyle. CT was superior to OR for detection of MC/MT3 proximal fissures and articular comminution, condylar small cracks and lucencies, and proximal sesamoid fractures. OR was superior to CT for detection of proximal P1 dorsal fractures. Both OR and CT were poor at detecting palmar/planter proximal P1 fractures and coalescing cracks in the subchondral bone of MC/MT3. Conclusions CT is better than OR for detection of pathology in limbs with condylar fractures, but does not detect every pathologic feature. Clinical Relevance CT provides superior information of pathology in Thoroughbred racehorses with condylar fractures. [ABSTRACT FROM AUTHOR]

The purpose of this study was to create a controlled partial thickness cartilage lesion in a sheep model, and to provide a foundation to study the natural history of the progression of this lesion. Twenty-eight sheep divided into four groups (1, 12, 24, and 52 weeks, n = 7/group) were used in this study. In one stifle, a mechanical tool was used to create a 200 µm partial thickness lesion (1.5 × 1.5 cm2) on the medial femoral condyle via arthroscopy. Joint fluid was drawn presurgery and after euthanasia for analysis of collage II 3/4 C long (C2C). After euthanasia, the condyle was analyzed by gross appearance, confocal laser microscopy (CLM) for cell viability, scanning electronic microscopy (SEM) for surface roughness, Artscan for cartilage stiffness, and histology for cartilage morphology. The gross appearance of the treated area appeared rough, soft, and swollen compared to untreated control over time. CLM demonstrated that the depth of cell death increased to 590 µm at 52 weeks after surgery. SEM demonstrated that the treated area became more irregular over time. Stiffness of the treated area was significantly less than control by 12 weeks after surgery. Histologic analysis demonstrated that the 12, 24, and 52 week groups had significantly poorer histologic scores than the 1 week group. Joint fluid analysis demonstrated that the treatment group at 1 week had significant higher levels of C2C than the pretreatment baseline data. The results of this study demonstrated that partial thickness injury of cartilage continued to propagate and degenerate over time in this sheep model. Options for the prevention or treatment of this lesion may be tested using this model in the future. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1974-1982, 2006 [ABSTRACT FROM AUTHOR]

Objective Evaluation of the relationship between canine weight gain from 6 to 15 weeks of age and passive coxofemoral joint (CFJ) laxity at 16 weeks of age. Study Design Longitudinal cohort study. Animals Full- or half-sibling hounds (n=56). Methods Hounds were weighed weekly from 6 to 15 weeks of age. Individual average daily gain (ADG) was calculated for each week (weekly) and for the study (overall). PennHIP distraction index (DI) was determined for each CFJ at 16 weeks. Mixed effects linear models were evaluated for associations of DI (highest and mean) with 15-week weight and ADGs (actual or normalized). Left and right DIs were compared with a Student's paired t-test. Significance was set at P<.05. Trends were considered at P<.10. Results Mean (±SD) 16-week DI score and 15-week weight was 0.67±0.16 and 12.5±1.8 kg, respectively. Within animal left and right DIs were not significantly different. There were no significant associations between DI and any of the weight gains evaluated. There was a trend for a negative relationship between normalized 14-week ADG and DI in one statistical model. Conclusions Weight gain from 6 to 15 weeks of age was unrelated to 16-week PennHIP DI in a homogenous canine population with moderate-to-severe CFJ joint laxity. Clinical Relevance Based on our results, ad libitum feeding between 6 and 15 weeks of age does not appear to have an adverse impact on joint laxity at 16 weeks of age as measured by the PennHIP DI. [ABSTRACT FROM AUTHOR]

Chondromalacia can cause joint pain and synovial effusion with the potential for developing into osteoarthritis. Thermal chondroplasty using radiofrequency energy (RFE) has been reported to be superior to mechanical debridement for treating chondromalacia. We compared short-term changes in biomechanical properties of articular cartilage after treatment with monopolar (mRFE) or bipolar RFE (bRFE) or mechanical debridement (MD) on experimentally created grade II chondromalacia patellae. Chondromalacia patellae was created arthroscopically in both patellae of 15 ponies. Ten months after surgery, each patella was randomly assigned to one of four experimental groups: sham operated, untreated control; MD; bRFE; and mRFE. Animals were euthanized 6 months after treatment and fresh osteochondral sections were collected from the treated area, the border of the chondromalacic and nonchondromalacic area, and from two untreated areas for analysis of mechanical properties. The same areas were harvested from an additional six untreated ponies. The aggregate modulus (HA), Poisson's ratio (νs), and permeability (k) were determined for each area under creep indentation, and cartilage thickness was measured with a needle probe. The relation between zone of calcified cartilage (ZCC) and mechanical properties of hyaline cartilage (HC) was assessed histomorphometrically. Treated areas of all four groups had inferior mechanical properties compared at the same location. The treated and border areas had significantly lower HA values than the untreated areas. Permeability values showed significant differences between bRFE and other treated groups. Chondromalacic areas showed thinning of cartilage compared to nonchondromalacic areas. Biomechanical properties of the injured cartilage were inferior to nonchondromalacic cartilage regardless of the treatment type. mRFE had the highest stiffness value compared to other treatments and significantly higher values than MD. A significant correlation was observed between the mechanical properties of HC and ZCC thickness. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [ABSTRACT FROM AUTHOR]

Abstract: Defects in articular cartilage are often repaired with fresh osteochondral grafts. While fresh allografts provide viable chondrocytes, logistic limitations require surgical implantation within seven days of graft harvest. Here, we provide information on cold preservation of whole intact osteochondral materials that retains cartilage cell viability and function, and histologic and biochemical integrity for 28days. Canine femoral condyles were obtained and stored at 4°C for 14, 21 or 28days. At the end of the storage period, cartilage was assessed for cell viability, 35S uptake, proteoglycan content and histologic parameters. The most noticeable histologic change was reduced Safranin-O near the cartilage surface with 14days of cold preservation, but had recovered with 21 and 28days. Cartilage thicknesses did not vary significantly. Cell viability was >95% at 14days, 75–98% at 21days and reduced to 65–90% at 28days. Cell function measures showed that the level of 35SO4 incorporation was suppressed in samples stored at 4°C. However, no significant differences were seen among groups at 14, 21 or 28days of cold preservation. This data has implications for tissue banking protocols for osteochondral allograft material obtained for transplantation suggesting that cold preserved allograft material be implanted within 28days. [Copyright &y& Elsevier]

The objective of this study was to establish guidelines for the selection of an insulation material used to surround the electrode of radio frequency energy (RFE) probes used for thermal chondro plasty. These guidelines were established by identifying which insulation materials resulted in the least amount of con rcdrocyte death while smoothing the surface of chondromalacia cartilage. RFE causes electrolyte oscillation and molecular friction in the tissue to heat it and subsequently smooth the surface. Ma- [311 tertial properties investigated included the coefficient of thermal sec expansion (CTE), thermal conductivity (TC), and volume re sis- nac tibiad (VR). die Fresh human chondromalacia cartilage samples of Outer bridge h grades II and Ill were obtained from patients undergoing total C C knee arthroplasty. Stiffness measurements were taken retreat dement and post treatment. RFE was applied to a 1-cm area for that 15 s in a paintbrush treatment pattern. The insulation materials pit evaluated included Macro® (j CTE. J, TC, I VR; in relarention to GTE = 10 x 10-6/0 C @ 20 °C, TC = 3 W/mK, Vii = 1 x 10" ohm*cm), zirconia toughened alumina (ZTA) and 99.5% alumina (J. CTE, I TC, VR), alu- minium nitride (j GTE, I TC, 1 Vii), Teflon® (PTFE) a s (I CTE, j TC, I Vii), partially stabilized zirconia (YTZP) cor (j CTEJ TC,I VR),andUltem®(I CTEJ TC,4. Vii). or There were no significant differences between pretreatment and post treatment stiffness of the cartilage for any material invest- cet.. gated. Subjectively scored scanning electron microscopy (SEM) quz images revealed that the surfaces of all samples treated with RFE pro were relatively smooth with melted frond's. Prototype probes made gerl with Macro®, 99.5 % alumina, and ZTA had TC ≦ 30 W/mol*K anc and resulted in a mean of 35% less cell death (176 ± 56 pm, 130 ± 48 pm, and 114 ± 33 pm, respectively) than aluminum ma nitride, PTFE, and YTZP (246 ± 68 pm, 231 ± 108 pm, and fun 195 ± 89 pm, respectively). Macor®, 99.5% alumina, and ZTA sha prototype probes all had Vii hm*cm and resulted intc in a mean 37% less cell death than aluminum nitride or YTZP. re There was no apparent relationship between CTE and the depth of chondrocyte death. 7 [ABSTRACT FROM AUTHOR]

Following transplantation of ovine neocartilage allografts, 26 sheep were divided into groups according to the following weight-bearing schedule: 8-week nonweight bearing (8NWB, n=14), and 8-week nonweight bearing+4-week weight bearing (8NWB+4WB, n=12). In addition, 7 and 6 sheep, respectively, in the 8NWB and 8NWB+4WB groups received tTG treatment after allograft transplantation, whereas the remaining 13 sheep in these groups did not receive tTG. Finally, 8 sheep served as sham-operated controls without allograft transplantation. After euthanasia, stifle joints were harvested for the analysis of gross appearance, chondrocyte viability, histology, and biomechanical testing. No significant differences were noted in macroscopic graft survival and union with host tissue in both 8NWB and 8NWB+4WB groups between the tTG treated and non-tTG treated animals. Analysis of histological scores demonstrated no significant difference between tTG and non-tTG treatments in both 8NWB and 8NWB+4WB groups. Confocal laser microscopic analysis of the explanted defects revealed 70%-100% cell viability in all treatment groups. This study shows that allogeneic chondrocytes harvested from neonatal donors provide sufficient metabolic activity to affect repair. Use of tTG to augment resorbable suture fixation of neocartilage grafts provided no advantage over suture alone in this pilot study. [ABSTRACT FROM AUTHOR]

This study was designed to objectively quantify in vivo anterior–posterior canine knee translation relative to anterior cruciate ligament (ACL) integrity. Tibial translation was determined in one knee of 43 crossbreed hounds from radiographs performed while a set anterior and then posterior force was applied to the tibia using a custom designed device. The total (TTT), anterior (ATT), and posterior (PTT) tibial translation were measured (absolute) and normalized to the width of the tibia (normalized). Absolute and normalized TTT was significantly greater in ruptured ACL knees than in partially disrupted (PD) ACL knees, which were significantly greater than in intact ACL knees. ATT and PTT was significantly greater in ruptured ACL knees than in PD or intact ACL knees, which were not significantly different. The sensitivity and specificity of normalized TTT to distinguish knees with intact from PD ACLs were both 100%. Normalized TTT to distinguish knees with PD from ruptured ACLs had a sensitivity and specificity of 100% and 92%, respectively. Intra- and inter-observer intra-class correlation coefficients were 0.84 or higher for all translations. This precise non-invasive technique to assess canine knee translational stability and ACL integrity permits repetitive, objective measurements for diagnostic use and to assess therapeutic intervention efficacy. [Copyright &y& Elsevier]

Background: In this study, we evaluated the capacity of a single percutaneous injection of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in a rapidly resorbable calcium phosphate paste (alpha-BSM) to accelerate bone-healing in a canine tibial osteotomy model. We hypothesized that the osteotomy sites would heal faster after percutaneous delivery of rhBMP-2/alpha-BSM than they would after injection of alpha-BSM alone or after no treatment.Methods: Bilateral tibial osteotomy was performed and the sites were stabilized with external fixators in sixteen dogs. Four hours after the surgery, one limb of each dog was treated with a single percutaneous injection of rhBMP-2/alpha-BSM paste or an equal volume of alpha-BSM alone. There were eight limbs in each group, and the osteotomy site in the contralateral limb served as an untreated control. The results were evaluated with serial radiography and force-plate analysis at four and eight weeks after surgery and with mechanical testing and histologic examination at eight weeks after the surgery.Results: At four and eight weeks after the osteotomy and treatment, the scores for radiographic union were significantly greater for the rhBMP-2/alpha-BSM-treated limbs than they were for the alpha-BSM-treated or untreated, control limbs (p < 0.05). The callus area in the rhBMP-2/alpha-BSM-treated limbs was significantly greater than that in the alpha-BSM-treated and untreated, control limbs at four and eight weeks postinjection (p < 0.05). The time-integrated vertical force for the rhBMP-2-treated limbs was significantly greater than that for their contralateral controls at four weeks and significantly greater than that for the treated and control limbs of the alpha-BSM-treated dogs at four and eight weeks after the surgery (p Conclusions: This study demonstrates the capacity of a single percutaneous injection of rhBMP-2 delivered in a resorbable calcium phosphate paste (alpha-BSM) four hours after surgery to accelerate the healing of tibial osteotomy sites in a canine model. [ABSTRACT FROM AUTHOR]

Background: In this study, we evaluated the capacity of a single percutaneous injection of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in a rapidly resorbable calcium phosphate paste (α-BSM) to accelerate bone-healing in a canine tibial osteotomy model. We hypothesized that the osteotomy sites would heal faster after percutaneous delivery of rhBMP-2/(α-BSM than they would after injection of α-BSM alone or after no treatment. Methods: Bilateral tibial osteotomy was performed and the sites were stabilized with external fixators in sixteen dogs. Four hours after the surgery, one limb of each dog was treated with a single percutaneous injection of rhBMP-2/α-BSM paste or an equal volume of α-BSM alone. There were eight limbs in each group, and the osteotomy site in the contralateral limb served as an untreated control. The results were evaluated with serial radiography and force-plate analysis at four and eight weeks after surgery and with mechanical testing and histologic examination at eight weeks after the surgery. Results: At four and eight weeks after the osteotomy and treatment, the scores for radiographic union were significantly greater for the rhBMP-2/α-BSM-treated limbs than they were for the α-BSM-treated or untreated, control limbs (p < 0.05). The callus area in the rhBMP-2/α-BSM-treated limbs was significantly greater than that in the α-BSM-treated and untreated, control limbs at four and eight weeks post injection (p < 0.05). The time-integrated vertical force for the rhBMP-2-treated limbs was significantly greater than that for their contralateral controls at four weeks and significantly greater than that for the treated and control limbs of the α-BSM-treated dogs at four and eight weeks after the surgery (p ≤ 0.05). The rhBMP-2-treated limbs were significantly stiffer in bending and in torsion (p < 0.05) compared with the α-BSM-treated and control limbs. Histologic analysis demonstrated increased bone formation and more mature bone at the osteotomy site in the rhBMP-2-treated limbs compared with that in the α-BSM-treated and control limbs. Conclusions: This study demonstrates the capacity of a single percutaneous injection of rhBMP-2 delivered in a resorbable calcium phosphate paste α-BSM) four hours after surgery to accelerate the healing of tibial osteotomy sites in a canine model. Clinical Relevance: A single percutaneous injection of rhBMP-2/α-BSM may be useful as an adjuvant treatment to accelerate healing of bone defects similar to those created in this study. [ABSTRACT FROM AUTHOR]

Objective To quantify long-term bone adaptation after stable cemented total hip arthroplasty (cTHA) in dogs. Study Design Clinical study. Animals Fourteen dogs. Methods Femoral specimens were collected from client-owned dogs that were donated after death because of causes unrelated to their cTHA. Mean (±SEM) dog age was 11.4±0.7 years and implant duration was 5.3±0.7 years. Implant stability was established from radiographic signs and gross mechanical stability. Femurs were evaluated at 3 levels based on implant length: proximal stem (PS), mid-stem (MS), and distal to stem (DS). Cortical area, medullary area, and porosity were measured at each level. Implanted femurs were compared to contralateral nonimplanted femurs. Results Cortical area and cortical porosity were significantly increased in implanted femurs compared to nonimplanted femurs. Cortical area was increased at the MS and DS levels, and porosity was increased at the PS and MS levels in implanted femurs. Porosity was greatest in the endosteal region at the PS and MS levels in implanted femurs. Conclusions Significant differences in femoral geometry and cortical porosity were detected after long-term stable cTHA. Net bone loss proximally and increased bone mass distally support stress shielding as a important mechanical factor associated with bone adaptation. Distribution of porosity shifts to endosteal regions after long-term cTHA. Clinical Relevance Significant site-specific femoral adaptation occurs in response to stable cTHA and may precede implant loosening. [ABSTRACT FROM AUTHOR]

Objective To evaluate femoral adaptation after unstable long-term cemented total hip arthroplasty (cTHA) in dogs. Study Design Clinical study. Animals Four dogs. Methods Paired femurs were examined from client-owned dogs that were donated to a retrieval program after death from causes unrelated to their cTHA. Mean (±SEM) dog age was 10.0±1.5 years and implant duration was 6.0±1.4 years. Implanted femurs had radiographic changes associated with implant loosening and gross mechanical instability at femur retrieval. Femurs were evaluated at 3 levels relative to implant length. Cortical area and medullary area were measured at each level, and cortical porosity was assessed at each level in 4 quadrants and in 3 regions. Implanted femurs were compared with the contralateral non-implanted femurs. Results Cortical area and cortical porosity were increased at all levels in femurs with unstable implants. Implanted femurs had increased porosity in all quadrants and regions at the proximal 2 levels, and increased porosity in only the cranial quadrant and mid-cortical area at the distal level, when compared with contralateral non-implanted femurs. Corresponding medullary areas were not different. Conclusions Significant histomorphometric changes occur in femurs after unstable cTHA. The patterns of periosteal bone formation and endosteal bone resorption support mechanisms of stress shielding and wear debris-mediated osteolysis as factors that may contribute to femoral adaptation and implant loosening. Clinical Relevance Despite popularity and excellent return to function with cTHA, aseptic loosening remains a serious long-term complication. Substantial net bone loss and unfavorable environment with unstable cTHA may make revision surgery less successful. [ABSTRACT FROM AUTHOR]

Transection of the canine anterior cruciate ligament (ACL) is a well-established osteoarthritis (OA) model. This study evaluated a new method of canine ACL disruption as well as canine knee joint laxity and joint capsule (JC) contribution to joint stability at two time points (16 and 26 weeks) after ACL disruption (n=5/time interval). Ten crossbreed hounds were evaluated with force plate gait analysis and radiographs at intervals up to 34 weeks after monopolar radiofrequency energy (MRFE) treatment of one randomly selected ACL. Each contralateral ACL was sham treated. The MRFE treated ACLs ruptured approximately eight weeks (mean 52.5 days, SEM ± 1.0, range 48–56 days) after treatment. Gait analysis and radiographic changes were consistent with established canine ACL transection models of OA. Anterior–posterior (AP) translation and medial–lateral (ML) rotation were measured in each knee at 30°, 60°, and 90° of flexion with and then without JC with loads of 40 N in AP translation and 4 N m in ML rotation. A statistically significant interaction in AP translation included JC by cruciate (P=0.02), and there was a trend for a cruciate by time (P=0.07) interaction. Significant interactions in ML rotational testing included the presence of joint capsule (P=0.0001) and angle by cruciate (P=0.0012). This study describes a model in which canine ACLs predictably rupture approximately eight weeks after arthroscopic surgery and details the contribution of JC to canine knee stability in both ACL intact and deficient knees. The model presented here avoids the introduction of potential surgical variables at the time of ACL rupture and may contribute to studies of OA pathogenesis and inhibition. This model may also be useful for insight into the pathologic changes that occur in the knee as the ACL undergoes degeneration prior to rupture. [Copyright &y& Elsevier]

Presents a study which compared thermal chondroplasty with monopolar radiofrequency energy in a 37 degrees celsius lavage solution with that of a 22 degrees celsius lavage solution in terms of chondrocyte death and smoothing of the articular cartilage surface. Description of a method to limit chondrocyte death for temperature-controlled monopolar radiofrequency energy; Materials and methods used in the study; Results and discussion.

This study evaluated biomechanical properties of healing ligament following subfailure (grade II) injury by comparing young and mature animals in a rat lateral collateral ligament (LCL) model. One randomly selected LCL was stretched in situ using a custom designed device in eighteen young (21 days) and eighteen skeletally mature (8 months) male rats. Animals were euthanized at 0, 7, and 14 days post-surgery, and ligament ultimate stress, strain at failure and laxity were determined (n=6 pairs per group). At time 0 after introduction of stretch injury, ligament laxity was present in both groups. The mature rats had 54±9% strength of the control while the immature rats had 58±11% of the strength of the control, representing a consistent and significant injury. The immature and mature ligaments showed similar patterns of cellular damage post-injury and had similar modes of mechanical failure. Ligament laxity decreased in each group as healing time increased, however ligament laxity did not completely recover in either group after 2 weeks of healing. After 7 and 14 days of healing, the mature rats, respectively, had only 63±14% and 80±8% strengths of the controls while the immature rats had 94±6% and 94±10%. Hence, mechanical data showed that immature animals recovered their strength after a grade II sprain at a faster rate than mature animals. However, ligament laxity was still present in both groups two weeks after the injury and was not completely removed by growth in the immature group. These findings are clinically relevant since joint laxity after injury is common, and these results may explain the presence of continued instability in a joint injured at a young age. Hence, this study, with a new injury model, showed differences in ligament healing associated with maturity and quantified the clinically observed persistance of ligament laxity. [Copyright &y& Elsevier]

Provides information on a study that compared the effects of treatment with bipolar and monopolar radiofrequency energy on 30 osteochondral sections harvested from 22 patients with spontaneously occurring chondromalacia who were undergoing knee arthroplasty. Methodology of the study; Results and discussion on the study.