The effectiveness and mechanical properties of chemotherapy-impregnated cement in Ewing sarcoma.

Bone cement is often used in the surgical treatment of Ewing sarcoma (ES). Chemotherapy-impregnated cement (CIC) has never been tested in slowing ES growth. The purpose of the study is to determine if CIC can decrease cell proliferation, and to assess changes in the mechanical qualities of the cement. Chemotherapeutic agents including doxorubicin, cisplatin, etoposide, and SF2523 were mixed with bone cement. ES cells were plated and exposed to cell growth media that had contained CIC or regular bone cement (RBC) as a control, and cell proliferation assays were performed daily for 3 days. Mechanical testing on RBC and CIC was also performed. There was a significant decrease (p < 0.001) in cell proliferation among all cells treated with CIC compared to cells treated with RBC by 48 h postexposure. Additionally, there was a synergistic effectiveness of the CIC noted when multiple antineoplastic agents were combined. Three-point bending tests did not reveal substantial reductions in tolerated maximum bending load and maximal displacement at maximal bending load between CIC and RBC. Statement of Clinical Significance: CIC does appear to be effective at decreasing cell growth and does not appear to substantially alter the mechanical properties of the cement.

From the international space station to the clinic: how prolonged unloading may disrupt lumbar spine stability.

BACKGROUND CONTEXT: Prolonged microgravity exposure is associated with localized low back pain and an elevated risk of post-flight disc herniation. Although the mechanisms by which microgravity impairs the spine are unclear, they should be foundational for developing in-flight countermeasures for maintaining astronaut spine health. Because human spine anatomy has adapted to upright posture on Earth, observations of how spaceflight affects the spine should also provide new and potentially important information on spine biomechanics that benefit the general population. PURPOSE: This study compares quantitative measures of lumbar spine anatomy, health, and biomechanics in astronauts before and after 6 months of microgravity exposure on board the International Space Station (ISS). STUDY DESIGN: This is a prospective longitudinal study. SAMPLE: Six astronaut crewmember volunteers from the National Aeronautics and Space Administration (NASA) with 6-month missions aboard the ISS comprised our study sample. OUTCOME MEASURES: For multifidus and erector spinae at L3-L4, measures include cross-sectional area (CSA), functional cross-sectional area (FCSA), and FCSA/CSA. Other measures include supine lumbar lordosis (L1-S1), active (standing) and passive (lying) flexion-extension range of motion (FE ROM) for each lumbar disc segment, disc water content from T2-weighted intensity, Pfirrmann grade, vertebral end plate pathology, and subject-reported incidence of chronic low back pain or disc injuries at 1-year follow-up. METHODS: 3T magnetic resonance imaging and dynamic fluoroscopy of the lumbar spine were collected for each subject at two time points: approximately 30 days before launch (pre-flight) and 1 day following 6 months spaceflight on the ISS (post-flight). Outcome measures were compared between time points using paired t tests and regression analyses. RESULTS: Supine lumbar lordosis decreased (flattened) by an average of 11% (p=.019). Active FE ROM decreased for the middle three lumbar discs (L2-L3: -22.1%, p=.049; L3-L4: -17.3%, p=.016; L4-L5: -30.3%, p=.004). By contrast, no significant passive FE ROM changes in these discs were observed (p>.05). Disc water content did not differ systematically from pre- to post-flight. Multifidus and erector spinae changed variably between subjects, with five of six subjects experiencing an average decrease 20% for FCSA and 8%-9% for CSA in both muscles. For all subjects, changes in multifidus FCSA strongly correlated with changes in lordosis (r2=0.86, p=.008) and active FE ROM at L4-L5 (r2=0.94, p=.007). Additionally, changes in multifidus FCSA/CSA correlated with changes in lordosis (r2=0.69, p=.03). Although multifidus-associated changes in lordosis and ROM were present among all subjects, only those with severe, pre-flight end plate irregularities (two of six subjects) had post-flight lumbar symptoms (including chronic low back pain or disc herniation). CONCLUSIONS: We observed that multifidus atrophy, rather than intervertebral disc swelling, associated strongly with lumbar flattening and increased stiffness. Because these changes have been previously linked with detrimental spine biomechanics and pain in terrestrial populations, when combined with evidence of pre-flight vertebral end plate insufficiency, they may elevate injury risk for astronauts upon return to gravity loading. Our results also have implications for deconditioned spines on Earth. We anticipate that our results will inform new astronaut countermeasures that target the multifidus muscles, and research on the role of muscular stability in relation to chronic low back pain and disc injury.

Operative findings and complications associated with adjunctive hip arthroscopy in 95 hips undergoing periacetabular osteotomy.

PURPOSE: to report our initial experience with adjunctive hip arthroscopy and periacetabular osteotomy (PAO). METHODS: Retrospective review of patients who underwent PAO and ipsilateral hip arthroscopy between 2003 and 2013. Indications for arthroscopy were mechanical symptoms and/or positive magnetic resonance imaging to suggest intra-articular pathology including chondrolabral lesions, ligamentum teres tears and hypertrophy, and synovitis. Preoperative Tönnis arthritis grades, age, sex, operative findings and treatment, complications, and, if available, hip survival were recorded. RESULTS: Of 78 patients (95 hips) included, 64 (82%) were female and 14 (18%) male, average age was 30.6 (14-63) years. Tönnis grades were 0 in 40 hips (42%), 1 in 45 hips (47%), and 2 in 10 hips (11%). No Tönnis 3 hips were included. 84% of hips demonstrated labral pathology. 92% had chondromalacia, which was severe enough in 4 patients to warrant cancellation of PAO; all 4 have subsequently required total hip replacement at short-term follow-up. Labral debridement was performed in 73 hips and refixation in 7. 5 postoperative complications occurred - none major, including 1 fluid extravasation, 1 case of heterotopic ossification, and 3 transient neuropraxias. CONCLUSIONS: Intraarticular pathology is highly prevalent in patients undergoing PAO with mechanical symptoms, and can be safely managed by adjunctive arthroscopy. Complications were minimal in our series and are comparable to reports of PAO without arthroscopy. Arthroscopy can treat pathology that is inaccessible during standalone PAO and permits avoidance of routine arthrotomy, surgical dislocation, rectus release, and futile PAO in cases with severe articular damage.

Lumbar Spine Paraspinal Muscle and Intervertebral Disc Height Changes in Astronauts After Long-Duration Spaceflight on the International Space Station.

STUDY DESIGN: Prospective case series. OBJECTIVE: Evaluate lumbar paraspinal muscle (PSM) cross-sectional area and intervertebral disc (IVD) height changes induced by a 6-month space mission on the International Space Station. The long-term objective of this project is to promote spine health and prevent spinal injury during space missions and here on Earth. SUMMARY OF BACKGROUND DATA: National Aeronautics and Space Administration (NASA) crewmembers have a 4.3 times higher risk of herniated IVDs, compared with the general and military aviator populations. The highest risk occurs during the first year after a mission. Microgravity exposure during long-duration spaceflights results in approximately 5 cm lengthening of body height, spinal pain, and skeletal deconditioning. How the PSMs and IVDs respond during spaceflight is not well described. METHODS: Six NASA crewmembers were imaged supine with a 3 Tesla magnetic resonance imaging. Imaging was conducted preflight, immediately postflight, and then 33 to 67 days after landing. Functional cross-sectional area (FCSA) measurements of the PSMs were performed at the L3-4 level. FCSA was measured by grayscale thresholding within the posterior lumbar extensors to isolate lean muscle on T2-weighted scans. IVD heights were measured at the anterior, middle, and posterior sections of all lumbar levels. Repeated measures analysis of variance was used to determine significance at P < 0.05, followed by post-hoc testing. RESULTS: Paraspinal lean muscle mass, as indicated by the FCSA, decreased from 86% of the total PSM cross-sectional area down to 72%, immediately after the mission. Recovery of 68% of the postflight loss occurred during the next 6 weeks, still leaving a significantly lower lean muscle fractional content compared with preflight values. In contrast, lumbar IVD heights were not appreciably different at any time point. CONCLUSION: The data reveal lumbar spine PSM atrophy after long-duration spaceflight. Some FCSA recovery was seen with 46 days postflight in a terrestrial environment, but it remained incomplete compared with preflight levels. LEVEL OF EVIDENCE: 4.

Radiofrequency stimulation for potential healing of meniscal injuries in the avascular zone.

We conducted this study to evaluate the effect of radiofrequency (RF) stimulation with suture repair on the healing of tears in the meniscal white-white zone. Fifty-four New Zealand white rabbits underwent surgically induced meniscal injuries within the white-white region. RF was applied using a 0.8-mm TOPAZ MicroDebrider RF wand (ArthroCare) at level 4 for 500 milliseconds. Rabbits were sacrificed at 28 and 84 days for gross and histologic analysis by 3 blinded observers and at 9, 28, and 84 days for biochemical examination. Biochemical analyses included evaluation of cell proliferation (3H-thymidine), as well as mitogenic (IGF-1, bFGF) and angiogenic (VEGF, αV) factors. Of specimens repaired with RF combined with suture, 19 (58%) showed a degree of gross morphologic and histologic healing. No significant healing was seen in specimens with either no repair or repair with suture alone. We observed a 40% increase in cellular proliferation when RF supplementation was used (P<.05). With regards to mitogenic and angiogenic markers (IGF-1, bFGF, VEGF, and αV), there was a significant increase in groups treated with RF at 9 and 28 days (P>0.05). RF supplementation of avascular zone meniscal repairs may lead to an increased healing response.

Use of platelet-rich plasma to enhance tendon function and cellularity.

Clinical studies have shown inconsistent healing with subjective improvement after use of platelet-rich plasma (PRP) for tendinosis and partial tendon tears. We conducted a study to assess changes after injecting PRP into an intact rabbit patellar tendon (PT) model. In the study group (n = 10), an incision was made over the PT and PRP was injected into multiple sites on the PT. The control group (n = 8) was injected with saline. PTs were harvested 7 and 28 days after injection. Hematoxylin-eosin staining showed hypercellularity in the PRP group at 7 days, but the effect was not as marked at 28 days. At 7 days, polarized microscopy showed increased crimp density of collagen in the PRP group, compared with the control group, demonstrating up-regulation in collagen matrix. Cellular proliferation measured by tritiated thymidine was also significantly increased (P = .02) in the PRP group, compared with the control group, but the difference was not as significant at 28 days. At 7 and 28 days, there were no significant changes in basic fibroblast growth factor, insulin-like growth factor, vascular endothelial growth factor, or platelet-derived growth factor with 2B chains. Injection of PRP into rabbit PT enhances collagen remodeling and hypercellularity with increased metabolic activity, which could have a positive effect on healing.

Treatment of articular cartilage defects in the goat with frozen versus fresh osteochondral allografts: effects on cartilage stiffness, zonal composition, and structure at six months.

BACKGROUND: Understanding the effectiveness of frozen as compared with fresh osteochondral allografts at six months after surgery and the resultant consequences of traditional freezing may facilitate in vivo maintenance of cartilage integrity. Our hypothesis was that the state of the allograft at implantation affects its performance after six months in vivo. METHODS: The effect of frozen as compared with fresh storage on in vivo allograft performance was determined for osteochondral allografts that were transplanted into seven recipient goats and analyzed at six months. Allograft performance was assessed by examining osteochondral structure (cartilage thickness, fill, surface location, surface degeneration, and bone-cartilage interface location), zonal cartilage composition (cellularity, matrix content), and cartilage biomechanical function (stiffness). Relationships between cartilage stiffness or cartilage composition and surface degeneration were assessed with use of linear regression. RESULTS: Fresh allografts maintained cartilage load-bearing function, while also maintaining zonal organization of cartilage cellularity and matrix content, compared with frozen allografts. Overall, allograft performance was similar between fresh allografts and nonoperative controls. However, cartilage stiffness was approximately 80% lower (95% confidence interval [CI], 73% to 87%) in the frozen allografts than in the nonoperative controls or fresh allografts. Concomitantly, in frozen allografts, matrix content and cellularity were approximately 55% (95% CI, 22% to 92%) and approximately 96% (95% CI, 94% to 99%) lower, respectively, than those in the nonoperative controls and fresh allografts. Cartilage stiffness correlated positively with cartilage cellularity and matrix content, and negatively with surface degeneration. CONCLUSIONS: Maintenance of cartilage load-bearing function in allografts is associated with zonal maintenance of cartilage cellularity and matrix content. In this animal model, frozen allografts displayed signs of failure at six months, with cartilage softening, loss of cells and matrix, and/or graft subsidence, supporting the importance of maintaining cell viability during allograft storage and suggesting that outcomes at six months may be indicative of long-term (dys)function. CLINICAL RELEVANCE: Fresh versus frozen allografts represent the "best versus worst" conditions with respect to chondrocyte viability, but "difficult versus simple" with respect to acquisition and distribution. The outcomes described from these two conditions expand the current understanding of in vivo cartilage remodeling and describe structural properties (initial graft subsidence), which may have implications for impending graft failure.

Augmentation of tendon healing with butyric acid-impregnated sutures: biomechanical evaluation in a rabbit model.

BACKGROUND: Butyric acid (BA) has been shown to be angiogenic and to enhance transcriptional activity in tissue. These properties of BA have the potential to augment biological healing of a repaired tendon. PURPOSE: To evaluate this possibility both biomechanically and histologically in an animal tendon repair model. STUDY DESIGN: Controlled laboratory study. METHODS: A rabbit Achilles tendon healing model was used to evaluate the biomechanical strength and histological properties at 6 and 12 weeks after repair. Unilateral tendon defects were created in the middle bundle of the Achilles tendon of each rabbit, which were repaired equivalently with either Ultrabraid BA-impregnated sutures or control Ultrabraid sutures. RESULTS: After 6 weeks, BA-impregnated suture repairs had a significantly increased (P < .0001) Young's modulus and ultimate tensile strength relative to the control suture repairs. At 12 weeks, no statistical difference was observed between these measures. The histological data at 6 weeks demonstrated significantly increased (P < .005) vessel density within 0.25 mm of the repair suture in the BA-impregnated group. There was also an associated 42% increase in the local number of myofibroblasts in the BA samples relative to the controls at this time. By 12 weeks, these differences were not observed. CONCLUSION: Tendons repaired with BA-impregnated sutures demonstrated improved biomechanical properties at 6 weeks relative to control sutures, suggesting a neoangiogenic mechanism of enhanced healing through an increased myofibroblast presence. CLINICAL RELEVANCE: These findings demonstrate that a relatively simple alteration of suture material may augment early tendon healing to create a stronger repair construct during this time.

A biomechanical assessment of tendon repair after radiofrequency treatment.

After acute tendon injury, rapid mobilization prevents adhesions and improves the ultimate strength of the repair. Radiofrequency (RF) ablation is proposed to enhance angiogenesis in the early stages of healing. The mechanism and effect of RF have not yet been described in an animal model of tendon injury. To investigate the biomechanical effect of bipolar RF on acute injury in a rabbit model of partial Achilles tendon transection and suture repair, RF-treated tendon repairs were compared to untreated tendons. Cross-sectional area, Young's modulus, and ultimate tensile strength were determined. At 6 and 12 weeks after repair, RF-treated tendons had significant increases in cross-sectional area (P<.001; P< .0001) and ultimate tensile strength (P<.0001; P<.01). Young modulus of RF-treated tendons was increased at 6 weeks but not at 12 weeks (P<.01) Compared with untreated tendons, RF-treated tendons showed faster return to mechanical integrity. This may allow earlier rehabilitation.

Effect of light-emitting diode (LED) therapy on the development of osteoarthritis (OA) in a rabbit model.

OBJECTIVE: The objective of this study was to evaluate whether light-emitting diodes (LEDs) could be effective in a noninvasive, therapeutic device for the treatment of osteoarthritic (OA) knee joints. DESIGN: Five weeks following the anterior cruciate ligament transection (ACLT) of mature New Zealand White rabbits, the animal knees were exposed to LED stimulation at intervals of 10 min/day, 5 days/week for 5 weeks in the experimental group (n=7). The device used high intensity red and infrared (IR) LEDs with a total amount of energy delivered to the skin of 2.4 J/cm(2). Animals were sacrificed at 9 weeks postoperatively. Femoral surface gross morphology was evaluated with a modified Outerbridge classification and mRNA expression of catabolic and anabolic markers from femoral condyle cartilage and synovial tissue was assessed using RT-PCR. A control group was harvested 9 weeks following untreated ACLT. RESULTS: Gross morphometry of the control group showed four Grade II, two Grade III and one Grade IV (average 2.6) condyles macroscopically. The experimental group showed two Grade I and five Grade II (average 1.7) (Table 1). mRNA expression of aggrecan in the cartilage showed no difference between the groups, however type II collagen expression increased in the experimental group compared with control. TNF-α expression was significantly decreased in the experimental group compared to control. CONCLUSIONS: There was general preservation of the articular surface and decreased levels of inflammation in the osteoarthritic joints with the application of LED therapy. This may provide potential application as a noninvasive treatment.

Etanercept enhances preservation of osteochondral allograft viability.

BACKGROUND: Osteochondral allografts are an increasingly popular treatment for the repair of articular cartilage lesions. Current tissue bank protocols require bacteriological testing that takes from 21 to 28 days to process. During this time, tumor necrosis factor-alpha (TNF-α, a proapoptotic cytokine) is upregulated, resulting in loss of chondrocyte viability. To date, etanercept (a cytokine inhibitor) has not been studied in the current storage paradigm with the intention of preserving cell viability. PURPOSE: This study was undertaken to assess whether the addition of etanercept can improve the chondrocyte viability ofosteochondral allograft during storage. STUDY DESIGN: Controlled laboratory study. METHODS: Osteochondral allografts were harvested from 8 Boer goat femurs and placed into storage media and stored at 4°C for 28 days. The experimental group was supplemented with 10 µg/mL of etanercept. After storage, cell viability was assessed by live/dead staining and confocal microscopy. Specimens were also analyzed histologically and underwent histomorphologic analysis. TNF-α expression was measured with semiquantitative polymerase chain reaction. RESULTS: At 28 days, the percentage viability of the superficial zone in etanercept-treated allografts was maintained at significantly higher levels than those measured in the untreated group (69.3 ± 9.4 compared with 47.8 ± 19.1, P = .01). No difference was found histologically between the etanercept and the untreated group (ie, safranin O staining for glycosaminoglycan expression). Histomorphologic assessment showed no difference in indentation stiffness or roughness between groups. TNF-α expression was significantly decreased in the etanercept group compared to the untreated group. CONCLUSION: Etanercept was able to maintain cell viability of osteochondral allografts significantly better than the current storage paradigm after 28 days of storage. CLINICAL RELEVANCE: Maintaining the viability of the superficial zone will benefit outcomes by facilitating joint articulation via improved lubrication. Additionally, maintaining the cellular viability for increased periods of time may allow a greater window of time in which a suitable recipient may be found.

Can osteochondral grafting be augmented with microfracture in an extended-size lesion of articular cartilage?

BACKGROUND: Both microfracture and osteochondral autografting procedures have been useful in treating osteochondral lesions. HYPOTHESIS: Combining microfracture and osteochondral autografting procedures can extend the size of lesions that can be treated with either technique. STUDY DESIGN: Descriptive laboratory study. METHODS: Eight adult goats underwent osteochondral autograft transfer of a 4.5-mm femoral trochlea plug into an 8-mm full-thickness chondral defect. Microfracture was performed in the gap region surrounding the autograft. The animals were allowed normal activity until the end of the experiment at 6 months. At harvest, the knees were assessed grossly, and then evaluation was performed by histology, histomorphometry, biochemistry, and biomechanics. RESULTS: The osteochondral plugs healed well, with integration of the bone and preservation of the chondral cap. The chondral gap between the host site articular cartilage and the transferred plug had decreased from 3 mm at implant to less than 0.1 mm. Histologic analysis demonstrated regions of variable cartilage repair, with integration of the cartilage layer at some sites but incomplete healing at others. Histomorphometry demonstrated filling of the chondral gap to 75% to 85% of the normal volume. Biochemical analysis revealed greater than 90% type II collagen at most sites, with some areas containing 80% type II collagen. Biomechanical indentation testing indicated that the repaired area had variable thickness and stiffness, with a trend of increased stiffness in the bulk graft and decreased softness at the proximal microfracture interface site. CONCLUSION: The performance of a combined microfracture and osteochondral autograft transfer procedure to resurface a large chondral defect appears promising. CLINICAL RELEVANCE: This combined technique shows promise for treatment of large chondral defects with a single operative procedure with autogenous tissue that is safe and potentially would have a shorter period of rehabilitation, similar to that of osteochondral transfers and microfracture, in a cost-effective setting.