Evaluation of zoledronate, cytochalasin-D, and desferrioxamine on osseointegration in an intra-medullary femoral implant model.

OBJECTIVE: The rise in primary and revision surgeries utilizing joint replacement implants suggest the need for more reliable means of promoting implant fixation. Zoledronate-(Zol), cytochalasin-D-(cytoD), and desferrioxamine-(DFO) have been shown to enhance mesenchymal stem cell (MSC) differentiation into osteoblasts promoting bone formation. The objective was to determine whether Zol, cytoD, and DFO can improve fixation strength and enhance peri-implant bone volume about intra-medullary femoral implants. METHODS: 48 Sprague-Dawley female rats were randomized into four treatments, saline-control or experimental: Zol-(0.8 µg/µL), cytoD-(0.05 µg/µL), DFO-(0.4 µg/µL). Implants were placed bilaterally in the femoral canals following injection of treatment solution and followed for 28 days. Mechanical push-out testing and micro-CT were our primary evaluations, measuring load to failure and bone volume. Qualitative evaluation included histological assessment. Data was analyzed with a one-way ANOVA with Holm-Sidak mean comparison testing. RESULTS: Significant results included pushout tests showing an increase in maximum energy for Zol (124%) and cytoD (82%); Zol showed an increase in maximum load by 48%; Zol micro-CT showed increase in BV/TV by 35%. CONCLUSIONS: Our findings suggest that locally applied Zol and cytoD enhance implant mechanical stability. Bisphosphonates and actin regulators, like cytoD, might be further investigated as a new strategy for improving osseointegration.

Osteogenic benefits of low-intensity pulsed ultrasound and vibration in a rodent osseointegration model.

OBJECTIVES: Osseointegrated prostheses are increasingly used for amputees, however, the lengthy rehabilitation time of these prostheses remains a challenge to their implementation. The aim of this study was to investigate the ability of locally applied vibration or low-intensity pulsed ultrasound (LIPUS) to accelerate osseointegration and increase peri-implant bone volume. METHODS: A 4-week and 8-week rodent study were conducted in a femoral intramedullary implant model (control, vibration, LIPUS, and combined treatment) to determine effects on healing. Osseointegration was evaluated quantitatively through mechanical, µCT and histological evaluations. RESULTS: Maximum pushout load at 4 weeks increased with LIPUS relative to control (37.7%, P=0.002). Histologically, LIPUS and vibration separately increased peri-implant bone formation after 4 weeks relative to control. Vibration resulted in greater peri-implant bone after 8 weeks than all other groups (25.7%, P<0.001). However, no significant group differences in pushout load were noted at 8 weeks. CONCLUSIONS: Although vibration increased bone around implants, LIPUS was superior to vibration for accelerating osseointegration and increasing bone-implant failure loads at 4 weeks. However, the LIPUS benefits on osseointegration at 4 weeks were not sustained at 8 weeks.

The use of an IL1-receptor antagonist to reverse the changes associated with established tendinopathy in a rat model.

Interleukin-1 (IL1) is a cytokine that plays a role in inflammation and is a potential contributor to the inflammation present in tendinopathy. Its inhibition may be of use in the treatment of tendinopathy and has been a target for treatment. To evaluate how an IL1-receptor antagonist (IL1-RA) reverses pathologic changes associated with established patellar tendinopathy, we randomized 48 Sprague-Dawley retired breeder rats into three groups having weekly bilateral patellar tendon injections for 6 weeks. The control group received 0.1 mL saline for 6 weeks. The intervention groups were treated with 0.1 mL 2% carrageenan for 4 weeks. Beginning at week three, the IL1-RA group received 0.94 mg of the IL1-RA (2.5 mg/kg) added to the 0.1 mL 2% carrageenan and 0.94 mg of the IL1-RA alone for the final 2 weeks, while the CAR received 0.1 mL saline for the final 2 weeks. Animals were euthanized 6 weeks after initial injection. The CAR group demonstrated significantly (P < 0.05) shorter tendon lengths (7.81 ± 0.44 mm) than the control (8.25 ± 0.58 mm) and IL1-RA (8.34 ± 0.52 mm) group (P < 0.05). Macroscopically, plaque-like formations were reduced and margins of the tendon were more evident in the IL1-RA group compared to the CAR group. CAR group demonstrated significantly greater histopathologic changes (inflammatory cell density, disorganization of collagen, nuclear rounding, and angiogenesis) than the control and IL1-RA group. No significant difference in mechanical properties of the tendon was noted. These findings demonstrate IL1-RA can reduce pathologic changes in the patellar tendon in an established tendonitis model although did not demonstrate a difference in mechanical properties.

Bone changes after short-term whole body vibration are confined to cancellous bone.

OBJECTIVE: This study assessed femur properties in 80 adult female rats exposed to a range of whole body vibration amplitudes at 45 Hz over five weeks. Our hypothesis was that an optimal amplitude for whole body vibration would be apparent and would result in increased bone strength. METHODS: Animals were treated in five amplitude groups (0 g, 0.15 g, 0.3 g, 0.6 g, and 1.2 g peak), for 15 minutes per day, five days per week, for five weeks. Femur strength was assessed via: (1) three-point bending of the shaft, (2) cantilever bending of the neck, and (3) indentation of distal cancellous bone. Femoral bone mineral density, plasma prostaglandin E2 (PGE2) concentrations, cartilage thickness, and histopathologic properties were measured. RESULTS: Vibration doubled (P=0.039) cancellous bone stiffness in the 0.6 g and 1.2 g groups and induced a 74% increase in PGE2 concentrations (P=0.007). However, femoral densitometry and strength of the neck and shaft were unchanged and the cancellous bone indentation strength did not differ statistically (P=0.084). Cartilage thickness of vibrated groups at the medial condyle did not increase significantly (P=0.142) and the histopathologic grade did not change. There was no definitive optimal vibration amplitude. CONCLUSION: The benefits of vibration therapy over five weeks were confined to cancellous bone.

Static and dynamic single leg postural control performance during dual-task paradigms.

Combining dynamic postural control assessments and cognitive tasks may give clinicians a more accurate indication of postural control under sport-like conditions compared to single-task assessments. We examined postural control, cognitive and squatting performance of healthy individuals during static and dynamic postural control assessments in single- and dual-task paradigms. Thirty participants (female = 22, male = 8; age = 20.8 ± 1.6 years, height = 157.9 ± 13.0 cm, mass = 67.8 ± 20.6 kg) completed single-leg stance and single-leg squat assessments on a force plate individually (single-task) and concurrently (dual-task) with two cognitive assessments, a modified Stroop test and the Brooks Spatial Memory Test. Outcomes included centre of pressure speed, 95% confidence ellipse, squat depth and speed and cognitive test measures (percentage of correct answers and reaction time). Postural control performance varied between postural control assessments and testing paradigms. Participants did not squat as deep and squatted slower (P < 0.001) during dual-task paradigms (≤12.69 ± 3.4 cm squat depth, ≤16.20 ± 4.6 cm · s-1 squat speed) compared to single-task paradigms (14.57 ± 3.6 cm squat depth, 19.65 ± 5.5 cm · s-1 squat speed). The percentage of correct answers did not change across testing conditions, but Stroop reaction time (725.81 ± 59.2 ms; F2,58 = 7.725, P = 0.001) was slowest during single-leg squats compared to baseline (691.64 ± 80.1 ms; P = 0.038) and single-task paradigms (681.33 ± 51.5 ms; P < 0.001). Dynamic dual-task assessments may be more challenging to the postural control system and may better represent postural control performance during dynamic activities.

Submuscular Versus Subcutaneous Ulnar Nerve Transposition: A Cadaveric Model Evaluating Their Role in Primary Ulnar Nerve Repair at the Elbow.

PURPOSE: To investigate the length gained from subcutaneous and submuscular transposition of the ulnar nerve at the elbow. Specifically, the study aimed to define an expected nerve gap able to be overcome, and to determine if a difference between transposition techniques exists. METHODS: Eleven cadaveric specimens from the scapula to fingertip were procured. In situ decompression and mobilization of the ulnar nerve at the elbow followed by simulated laceration of the nerve was performed. Nerves were marked 5 mm from the laceration site to facilitate overlap measurement and to simulate nerve end preparation to viable fascicles before primary coaptation. Nerve ends were attached to spring gauges set at 100 g of tension (strain ≤ 10%). Measurements of nerve overlap were obtained in varying degrees of wrist (0°, 30°, 60°) and elbow (0°, 15°, 30°, 45°, 60°, 90°) flexion. Measurements were performed after in situ decompression and mobilization, and then repeated after both subcutaneous and submuscular transposition. RESULTS: Ulnar nerve transposition was found to increase nerve overlap at an elbow flexion of 30° or greater. No difference was seen between subcutaneous and submuscular transpositions at all wrist and elbow positions. In situ decompression and mobilization alone provided an average of 3.5 cm of length gain with the elbow extended. Transposition in conjunction with clinically feasible wrist and elbow flexion (30° and 60°, respectively) provided 5.2 cm of length gain. Controlling for mobilization, a statistically significant increase in overlap of approximately 2 cm was gained from transposition. CONCLUSIONS: Although mobilization combined with wrist and elbow flexion may afford substantial gap reduction and should be used initially when approaching proximal ulnar nerve lacerations, transposition should be considered when faced with a large nerve gap greater than 3 cm at the elbow. No difference was seen between submuscular and subcutaneous transposition techniques. CLINICAL RELEVANCE: This study defines the extent an ulnar nerve gap at the elbow can be overcome by in situ mobilization, joint positioning, and transposition. It additionally compares the efficacy of submuscular and subcutaneous transposition techniques in closing this gap.

Immediate effect of vibratory stimuli on quadriceps function in healthy adults.

INTRODUCTION: The purpose of this study was to compare the effect of whole body vibration (WBV) and local muscle vibration (LMV) on quadriceps function. METHODS: Sixty adults were randomized to WBV, LMV, or control groups. Quadriceps function [Hoffmann (H)-reflex, active motor threshold (AMT), motor evoked potential (MEP) and electromyographic amplitude, peak torque (PT), rate of torque development (RTD), and central activation ratio (CAR)] was assessed before and immediately after and 10 and 20 minutes after interventions. RESULTS: WBV improved PT, CAR, AMT, EMG, and MEP amplitude, and EMG amplitude and CAR were greater than control after application. LMV improved EMG amplitude and AMT, and EMG amplitude was greater than control after application. AMT remained lower 10 and 20 minutes after WBV and LMV. No differences were noted between LMV and WBV. Vibration did not influence H-reflex or RTD. CONCLUSIONS: WBV and LMV increased quadriceps function and may be used to enhance the efficacy of strengthening protocols. Muscle Nerve 54: 469-478, 2016.

Whole-Body and Local Muscle Vibration Immediately Improve Quadriceps Function in Individuals With Anterior Cruciate Ligament Reconstruction.

OBJECTIVE: To determine the immediate effects of a single session of whole-body vibration (WBV) and local muscle vibration (LMV) on quadriceps function in individuals with anterior cruciate ligament reconstruction (ACLR). DESIGN: Singe-blind, randomized crossover trial. SETTING: Research laboratory. PARTICIPANTS: Population-based sample of individuals with ACLR (N=20; mean age ± SD, 21.1±1.2y; mean mass ± SD, 68.3±14.9kg; mean time ± SD since ACLR, 50.7±21.3mo; 14 women; 16 patellar tendon autografts, 3 hamstring autografts, 1 allograft). INTERVENTIONS: Participants performed isometric squats while being exposed to WBV, LMV, or no vibration (control). Interventions were delivered in a randomized order during separate visits separated by 1 week. MAIN OUTCOME MEASURES: Quadriceps active motor threshold (AMT), motor-evoked potential (MEP) amplitude, Hoffmann reflex (H-reflex) amplitude, peak torque (PT), rate of torque development (RTD), electromyographic amplitude, and central activation ratio (CAR) were assessed before and immediately after a WBV, LMV, or control intervention. RESULTS: There was an increase in CAR (+4.9%, P=.001) and electromyographic amplitude (+16.2%, P=.002), and a reduction in AMT (-3.1%, P<.001) after WBV, and an increase in CAR (+2.7%, P=.001) and a reduction in AMT (-2.9%, P<.001) after LMV. No effect was observed after WBV or LMV in H-reflex, RTD, or MEP amplitude. AMT (-3.7%, P<.001), CAR (+5.7%, P=.005), PT (+.31Nm/kg, P=.004), and electromyographic amplitude (P=.002) in the WBV condition differed from the control condition postapplication. AMT (-3.0% P=.002), CAR (+3.6%, P=.005), and PT (+.30Nm/kg, P=.002) in the LMV condition differed from the control condition postapplication. No differences were observed between WBV and LMV postapplication in any measurement. CONCLUSIONS: WBV and LMV acutely improved quadriceps function and could be useful modalities for restoring quadriceps strength in individuals with knee pathologies.

Comparison of fixation methods after anteromedialization osteotomy of the tibial tubercle for patellar instability.

PURPOSE: The aim of this study was to evaluate the biomechanical strength of two 4.5-mm screws and three 3.5-mm screws for fixation of the tibial tubercle after anteromedialization osteotomy. METHODS: Anteromedialization of the tibial tubercle was performed on 5 pairs of fresh-frozen cadaveric lower extremities. One leg from each pair was randomized to fixation with two 4.5-mm screws and the contralateral leg to fixation with three 3.5-mm screws. Each specimen was loaded cyclically to simulate an active straight-leg raise and then to failure while displacement of the tubercle fragment was recorded. RESULTS: There was no difference in mean tubercle fragment displacement under cyclic loading at any cycle number (P > .352). Maximum failure load for osteotomies secured with two 4.5-mm screws was 1,459 ± 540 N, and for three 3.5-mm screws it was 1,360 ± 707 N. This was not a statistically significant difference (P = .723). Tubercle migration of 7 mm was chosen as clinical failure. At this amount of displacement, mean load was 1,085 ± 398 N and 764 ± 313 N in the 4.5-mm and 3.5-mm groups, respectively, which was also not significantly different (P = .146). CONCLUSIONS: Both 2 × 4.5-mm and 3 × 3.5-mm screw constructs after tibial tubercle anteromedialization are equally capable of withstanding physiologic forces like those encountered during an active straight-leg raise and have similar failure strength. CLINICAL RELEVANCE: Although both configurations are comparable, the use of the smaller 3.5-mm screws may reduce the need for hardware removal related to prominence and soft tissue irritation.

The assessment of postural control with stochastic resonance electrical stimulation and a neoprene knee sleeve in the osteoarthritic knee.

OBJECTIVE: To determine whether the combination of stochastic resonance (SR) electrical stimulation and a neoprene knee sleeve could improve center of pressure (COP) measures of postural sway during single-leg stance in those with knee osteoarthritis (OA). DESIGN: Counterbalanced, repeated-measures intervention study of osteoarthritic adults during 6 different testing conditions: a control condition-control 1 (1); a counterbalance sequence of 4 treatment conditions-no stimulation with sleeve (2), 75% stimulation with sleeve (3), 100% stimulation with sleeve (4), and 150% stimulation with sleeve (5); and a second control condition-control 2 (6). SETTING: University sports medicine research laboratory. PARTICIPANTS: Subjects (N=52) with radiographically determined, minimal-to-moderate medial knee OA. INTERVENTIONS: Neoprene knee sleeve and SR electrical stimulation. MAIN OUTCOME MEASURES: COP displacement in the medial-lateral and anterior-posterior directions was collected to resolve the mean velocity, SD, range, and total path length. RESULTS: No significant differences were found in the study measures between the testing conditions. Additionally, no significant differences were found between the 3 stimulation conditions or between the sleeve-alone and stimulation conditions for any of the study measures. CONCLUSIONS: There were no significant improvements in balance with the use of a neoprene knee sleeve. Additionally, there was no added benefit of the SR stimulation as applied in the current configuration in this population.

Some observations on the subfibrillar structure of collagen fibrils as noted during treatment with NKISK and cathepsin G with mechanical agitation.

We observed the structure of collagen fibrils in rat tail tendons after treatment with NKISK and cathepsin G. NKISK is a pentapeptide that has been previously shown to bind fibronectin, while cathepsin G is a serine protease that cleaves fibronectin but not type I collagen. In tendons treated with NKISK, fibrils were seen to extensively dissociate into smaller-diameter subfibrils. These subfibrils were homogeneous in diameter with an average diameter of 26.3 ± 5.8 nm. Similar, although less extensive, dissociation into subfibrils was found in tendons treated with cathepsin G. The average diameter of these subfibrils was 24.8 ± 4.9 nm. The ability of NKISK and cathepsin G to release subfibrils at physiological pH without harsh denaturants may enhance the study of the subfibrillar structure of collagen fibrils.

Repair of lesser tuberosity osteotomy for shoulder arthroplasty: biomechanical evaluation of the Backpack and Dual Row techniques.

BACKGROUND: Subscapularis dysfunction following total shoulder arthroplasty can result in permanent loss of function. The lesser tuberosity osteotomy (LTO) has been proposed as a method which utilizes bone-to-bone healing to improve subscapularis function. This study evaluates the biomechanical properties of two described techniques for LTO repair. We hypothesized that a Dual Row repair would be stronger and demonstrate less cyclic displacement than a Backpack repair. MATERIALS AND METHODS: Ten matched pairs of cadaveric humeri were dissected, leaving the subscapularis intact, and a lesser tuberosity osteotomy was performed. Matched shoulders were randomized to either a Backpack repair or a Dual Row repair. Repairs were subjected to cyclic loading to 180 N for 500 cycles, followed by ramp-up loading to ultimate failure. Clinical failure was defined as displacement >5 mm after 500 cycles. RESULTS: Displacement after 500 cycles was significantly greater for the Backpack repair (6.9 mm) than for the Dual Row repair (4.6 mm) (P = .007). Most displacement occurred on the first cycle (Backpack, 4.6 mm; Dual Row, 2.1 mm) (P < .001). There was a trend toward a higher clinical failure rate for the Backpack repair (8/10) than the Dual Row repair (3/10). Ultimate tensile strength was significantly greater for the Dual Row repair (632.3 N) than for the Backpack repair (510.9 N) (P = .01). CONCLUSION: The Dual Row technique is significantly stronger and demonstrates less cyclic displacement than the Backpack technique. Clinical studies are needed to determine the impact of LTO repair technique on subscapularis function following shoulder arthroplasty.

Interleukin-1 receptor antagonist inhibits arthrofibrosis in a post-traumatic knee immobilization model.

BACKGROUND: Therapies for arthrofibrosis after knee surgery are needed to prevent loss of joint function. Interleukin-1 receptor antagonists (IL-1RA) have shown promise in treating established arthrofibrosis in pilot clinical studies. The objective of this study was to evaluate the ability of intra-articular injection of IL-1RA to prevent knee joint contracture in a post-traumatic knee immobilization model. METHODS: 20 male Sprague Dawley rats were block randomized into two groups: control and IL-1RA. Rats underwent intra-articular surgical trauma of the right knee with placement of an immobilization suture, securing the knees in 150° flexion. On post-operative days 1 and 8, each group received a 0.1 ml intra-articular injection of either saline (control) or anakinra (IL-1RA:single dosage; 2.63 mg/kg). Rats were euthanized fourteen days after surgery and the immobilization femorotibial angles were measured on the operative limbs with the suture and musculature intact. Subsequently, musculature was removed and femorotibial angles were measured in the operative and non-operative limbs with a defined extension moment applied with the posterior capsule intact or cut. A contracture angle was calculated as the angular difference between the operative and non-operative limb. RESULTS: The immobilization knee flexion angle did not differ (P = 0.761) between groups (control: 152 ± 9; IL-1RA: 150 ± 11). The joint contracture angles (smaller angle = improved outcome) were reduced by 12 degrees on average in the IL-1RA group compared to the control for both the capsule intact (P = 0.024) and cut (P = 0.019) states. CONCLUSIONS: Intra-articular IL-1RA injection was found to diminish knee extension deficits associated with arthrofibrosis in a post-traumatic joint immobilization model.

Prostaglandin E(2), collagenase, and cell death responses depend on cyclical load magnitude in an explant model of tendinopathy.

Tendinopathy is a significant clinical problem that can result from repetitive activity. While the precise etiology of this condition remains unclear, the cellular response to cyclical loading is believed to have a contributory role to the pathology of tendinopathy. This study examined the short-term biochemical response of avian flexor digitorum profundus tendon to repetitive cyclic loadings of varying magnitude. An in vitro tendon explant model was utilized to apply four levels of haversine tensile stress (peak stress of 0, 3, 12, and 18 MPa) at 1.0 Hz, 8 hr/day for 3 days. The 12 and 18 MPa levels were known to cause significant mechanical damage based on previous work. Tissue media was recovered and analyzed for prostaglandin E(2) (PGE(2)), lactate dehydrogenase (LDH, measure of cell death), and collagenase levels. Tissue samples were recovered and analyzed for cell viability, total collagen, and sulfated glycosaminoglycan content. Collagenase, LDH, and PGE(2) levels were found to be influenced by loading magnitude (p < 0.05) with higher levels being present at higher load magnitudes. Varying cyclical load magnitude caused minimal compositional changes as collagen content and glycosaminoglycan did not change. These results indicate that elevated cyclical mechanical loading of tendon quickly results in altered biochemical tissue responses indicative of tissue injury. More sustained cyclical loading over time may be required for these initial responses to induce more dramatic tissue changes as observed in clinical tendinopathy.

Effect of local zoledronic acid administration in a rat model of posterolateral spinal fusion.

STUDY DESIGN: Randomized animal model study. PURPOSE: Posterolateral spinal fusion represents a common surgical procedure in the United States. The effect of bisphosphonate administration in these patients is poorly understood. The purpose of this study is to determine whether local administration of bisphosphonate by soaking bone autograft would affect the apparent bone density or structural properties of the fusion mass in a rat model of posterolateral spinal fusion. METHODS: 36 Spring Dawley rats underwent L4-5 posterolateral spinal fusion with bone autograft. These rats were divided into three groups, two experimental groups and one control group. Each of the experimental groups underwent spinal fusion with morselized vertebral cortical and cancellous autograft soaked in zoledronic acid solution; one group 20 mcg/mL, another 200 mcg/mL. The control group underwent L4-5 spinal fusion with cancellous allograft soaked with saline. At 8 weeks, the rats were euthanized for analysis. Evaluations consisted of micro-CT scanning, four-point bending biomechanical testing, histology, and radiographs. RESULTS: Both of the experimental groups showed statistically significant increase in apparent bone density and bone volume fraction at the fusion mass. Biomechanical measures revealed a trend for improvement in the experimental groups, but these did not reach statistical significance. CONCLUSIONS: This data suggest that locally administered bisphosphonate medications result in increased apparent bone density and bone volume fraction at the fusion mass in posterolateral spinal fusion, and that there appear to be no deleterious consequences with regards to the stiffness or maximum load to failure of the fusion mass under flexion bending evaluation.

Locally delivered minocycline microspheres do not impair osseointegration of titanium implants in a rat femur model.

BACKGROUND: The purpose of this study was to determine whether intramedullary administration of extended-release minocycline microspheres would affect osseointegration. METHODS: Twenty-two rats were randomized to minocycline or saline femoral intramedullary injection followed by implantation of titanium alloy rods. Following euthanasia at four-weeks, pushout testing was performed and bone-volume-fraction assessed. RESULTS: Pushout strength was marginally greater in minocycline-treated implants (122.5 ± 39.1 N) compared to saline (96.9 ± 26.1 N) (P = 0.098). No difference was observed in energy to maximum load, mean stiffness, or peri-implant bone-volume-fraction (P > 0.05). CONCLUSIONS: Peri-implant minocycline administration did not impair implant fixation strength or peri-implant bone-volume, supporting its potential utility as an adjunct to intramedullary implants.

Effect of Nerve-Cutting Technique on Nerve Microstructure and Neuroma Formation.

Background Peripheral neuroma formation results from partial or complete nerve division. Elucidating measures to prevent the development of peripheral neuromas is of clinical importance. The aim of this study was to determine the effect of various surgical nerve-cutting techniques on nerve microstructure and resultant neuroma formation. Methods Twenty Sprague-Dawley rats were randomly assigned to one of the following nerve-cutting techniques: No. 15 scalpel blade with tongue depressor, micro-serrated scissors, nerve-cutting guide forceps with straight razor, and bipolar cauterization. The right sciatic nerve was transected using the assigned nerve-cutting technique. Neuromas were harvested 6 weeks postoperatively, and samples were obtained for histologic analysis. The contralateral sciatic nerve was transected at euthanasia and analyzed with histology and with scanning electron microscopy in a subset of the rats. Results Fifteen of the 20 rats survived the 6-week experiment. Scanning electron microscopy of the No. 15 scalpel blade group showed the most visual damage and disorganization whereas the nerve-cutting guide forceps and micro-serrated scissors groups resulted in a smooth transected surface. Bipolar cauterization appeared to enclose the fascicular architecture within a sealed epineurium. Each neuroma was significantly larger than contralateral controls. There were no significant differences in neuroma caliber between nerve transection groups. No substantial differences in microstructure were evident between transection groups. Conclusion Despite disparate microscopic appearances of the cut surfaces of nerves using various nerve-cutting techniques, we found no significant differences in the caliber or incidence of neuroma formation based on nerve-cutting technique. Nerve-cutting technique used when transecting peripheral nerves may have little bearing on the formation or size of resultant neuroma formation.

Minocycline microspheres did not significantly improve outcomes after collagenase injection of tendon.

BACKGROUND: Tetracycline antibiotics inhibit matrix metalloproteinases and pro-inflammatory cytokines implicated in the pathogenesis of tendinopathy, while microsphere formulations allow sustained release of drug contents. The purpose of this study was to evaluate the ability of a local minocycline microsphere injection to restore normal tendon properties in a rat model of collagenase-induced patellar tendinopathy. METHODS: A total of 22 rats were randomly assigned to the control (n = 11) or minocycline (n = 11) group and received bilateral patellar tendon injections of collagenase. After 7 days, the minocycline group received the minocycline microsphere treatment and the control group received phosphate buffered solution. Pain was assessed via activity monitors and Von Frey filament testing. At 4 weeks post-collagenase injections, animals were euthanized. RESULTS: Cage crossings significantly decreased among all rats 2-3 days following each injection period, however, tactile allodynia measures did not reflect this injury response. Biomechanical properties, interleukin-1 beta levels, and glycosaminoglycan content did not differ between groups. While not statistically significant, levels of leukotriene B4 were lower in the minocycline group compared to controls (p = 0.061), suggesting a trend. CONCLUSIONS: Our study further characterizes the collagenase model of tendinopathy by demonstrating no evidence of central sensitization with collagenase-induced injury. We found no adverse effect of intratendinous injections of minocycline-loaded poly-lactic-co-glycolic acid microspheres, although no therapeutic effect was observed. Future studies involving a more substantial tendon injury with a greater inflammatory component may be necessary to more thoroughly evaluate the effects of minocycline on tendon pathology.

Deferoxamine-Soaked Suture Improves Angiogenesis and Repair Potential After Acute Injury of the Chicken Achilles Tendon.

BACKGROUND: A major obstacle to the treatment of soft tissue injuries is the hypovascular nature of the tissues. Deferoxamine (DFO) has been shown to stimulate angiogenesis by limiting the degradation of intracellular hypoxia-inducible factor 1-alpha. HYPOTHESIS: DFO-saturated suture would induce angiogenesis and improve the markers of early healing in an Achilles tendon repair model. STUDY DESIGN: Controlled laboratory study. METHODS: Broiler hens were randomly assigned to the control (CTL) group or DFO group (n = 9 per group). The right Achilles tendon was partially transected at its middle third. The defect was surgically repaired using 3-0 Vicryl suture soaked in either sterile water (CTL group) or 324 mM DFO solution (DFO group). All animals were euthanized 2 weeks after the injury, and the tendon was harvested. Half of the tendon was used to evaluate angiogenesis via hemoglobin content and tissue repair via DNA content and proteoglycan (PG) content. The other half of the tendon was sectioned and stained with hematoxylin and eosin, safranin O, and lectin to evaluate vessel density. RESULTS: Hemoglobin content (percentage of wet tissue weight) was significantly increased in the DFO group compared with the CTL group (0.081 ± 0.012 vs 0.063 ± 0.016, respectively; P = .046). DNA content (percentage of wet tissue weight) was also significantly increased in the DFO group compared with the CTL group (0.31 ± 0.05 vs 0.23 ± 0.03, respectively; P = .024). PG content (percentage of wet tissue weight) was significantly decreased in the DFO group compared with the CTL group (0.26 ± 0.02 vs 0.33 ± 0.08, respectively; P = .035). Total chondroid area (number of vessels per mm2 of tissue area evaluated) was significantly decreased in the DFO group compared with the CTL group (17.2 ± 6.6 vs 24.6 ± 5.1, respectively; P = .038). Articular zone vessel density (vessels/mm2) was significantly increased in the DFO group compared with the CTL group (7.1 ± 2.5 vs 2.1 ± 0.9, respectively; P = .026). CONCLUSION: The significant increase in hemoglobin content as well as articular zone vessel density in the DFO group compared with the CTL group is evidence of increased angiogenesis in the fibrocartilaginous region of the tendon exposed to DFO. The DFO group also displayed a significantly greater level of DNA and significantly lower level of PG, suggesting enhanced early healing by fibrous tissue formation. CLINICAL RELEVANCE: Stimulating angiogenesis by DFO-saturated suture may be clinically useful to improve healing of poorly vascularized tissues.

Improved osseointegration with as-built electron beam melted textured implants and improved peri­implant bone volume with whole body vibration.

Transcutaneous osseointegrated prostheses provide stable connections to the skeleton while eliminating skin lesions experienced with socket prosthetics. Additive manufacturing can create custom textured implants capable of interfacing with amputees' residual bones. Our objective was to compare osseointegration of textured surface implants made by electron beam melting (EBM), an additive manufacturing process, to machine threaded implants. Whole body vibration was investigated to accelerate osseointegration. Two cohorts of Sprague-Dawley rats received bilateral, titanium implants (EBM vs. threaded) in their tibiae. One cohort comprising five groups vibrated at 45 Hz: 0.0 (control), 0.15, 0.3, 0.6 or 1.2 g was followed for six weeks. Osseointegration was evaluated through torsional testing and bone volume fraction (BV/TV). A second cohort, divided into two groups (control and 0.6 g), was followed for 24 days and evaluated for resonant frequency, bone-implant contact (BIC) and fluorochrome labeling. The EBM textured implants exhibited significantly improved mechanical stability independent of vibration, highlighting the benefits of using EBM to produce custom textured surfaces. Bone formation on and around the EBM textured implants increased compared to machined implants, as seen by BIC and fluorescence. No difference in torque, BIC or fluorescence among vibration levels was detected. BV/TV significantly increased at 0.6 g compared to control for both implant types.