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Selected AbstractsIFORS: the formative yearsINTERNATIONAL TRANSACTIONS IN OPERATIONAL RESEARCH, Issue 2 2000G.K. Rand In 1999 IFORS (The International Federation of Operational Research Societies) celebrated 40 years since its formation. The purpose of this article is to explain how it came into being following the first international conference in Operational Research, and to examine the foundations that were laid in the years leading up to its first General Meeting, held at the second international conference. A further article will examine several themes in IFORS' subsequent history. [source] Improving between-day kinematic reliability using a marker placement deviceJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2010Brian Noehren Abstract 3D motion analysis is commonly used to measure clinical outcomes, involving repeated measures over time. However, the day-to-day reliability of these measurements has been questioned and few attempts have been made to improve this reliability. Our purpose was to determine if a marker placement device (MPD) could improve day-to-day kinematic reliability as compared to manual marker placement. Ten healthy runners participated. Day-to-day comparisons of peak angles were made between manual marker placement and the use of an MPD. Reliability of each method was determined with intraclass correlation coefficients (ICC) and standard errors of measurement (SEM). The ICC and SEM values improved with the MPD. With the MPD, 7 out of 9 ICC values were >0.9 compared to only 3 when using manual marker placement. Additionally, the largest reduction in SEM values was in the transverse plane. Use of the MPD increases the power to detect smaller differences in studies of where gait is assessed over time. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1405,1410, 2010 [source] A comparison of cyclic variations in anterior knee laxity, genu recurvatum, and general joint laxity across the menstrual cycleJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2010Sandra J. Shultz Abstract Changes in anterior knee laxity (AKL), genu recurvatum (GR) and general joint laxity (GJL) were quantified across days of the early follicular and early luteal phases of the menstrual cycle in 66 females, and the similarity in their pattern of cyclic variations examined. Laxity was measured on each of the first 6 days of menses (M1,M6) and the first 8 days following ovulation (L1,L8) over two cycles. The largest mean differences were observed between L5 and L8 for AKL (0.32,mm), and between L5 and M1 for GR (0.56°) and GJL (0.26) (p,<,0.013). At the individual level, mean absolute cyclic changes in AKL (1.8,±,0.7,mm, 1.6,±,0.7,mm), GR (2.8,±,1.0°, 2.4,±,1.0°), and GJL (1.1,±,1.1, 0.7,±,1.0) were more apparent, with minimum, maximum and delta values being quite consistent from month to month (ICC2,3,=,0.51,0.98). Although the average daily pattern of change in laxity was quite similar between variables (Spearman correlation range 0.61 and 0.90), correlations between laxity measures at the individual level were much lower (range ,0.07 to 0.43). Substantial, similar, and reproducible cyclic changes in AKL, GR, and GJL were observed across the menstrual cycle, with the magnitude and pattern of cyclic changes varying considerably among females. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1411,1417, 2010 [source] The quadriga effect revisited: Designing a "safety incision" to prevent tendon repair rupture and gap formation in a canine model in vitroJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2010Hugo Giambini Abstract Loss of experimental animals due to tendon repair failure results in the need for additional animals to complete the study. We designed a relief proximal to the flexor digitorum profundus (FDP) tendon repair site to serve as a "safety incision" to prevent repair site ruptures and maximize safety incision-to-suture strength. The FDP tendons were dissected in 24 canine forepaws. The 2nd and 5th tendons were lacerated at the proximal interphalangeal joint level and sutured using a modified Kessler technique and peripheral running suture. Tendon width was measured where the FDP tendon separates into each individual digit and a safety incision, equal to the 2nd and 5th tendon widths, was performed 3, 4, or 5,mm (Groups 1, 2, and 3) proximal to the separation. The tendons were pulled at a rate of 1,mm/s until either the "safety incision" ruptured or the repair failed. There was no gap formation at the repair site in Groups 1 and 2. However, all Group 3 tendons failed by repair site rupture with the safety incision intact. An adequate safety incision to protect repair gap and rupture and maintain tendon tension for the FDP animal model should be about 4,mm from where the FDP tendon separates. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1482,1489, 2010 [source] Kynurenine inhibits chondrocyte proliferation and is increased in synovial fluid of patients with septic arthritisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2010Tim T. Lögters Abstract Kynurenine, the major degradation product of tryptophan has been shown to directly damage various tissues. Its potential contribution to septic arthritis is unknown. In this study, we analyzed the putative diagnostic value of kynurenine for bacterial joint infection and its potential harmful effects on cartilage. In a prospective study 41 patients with a joint effusion who had undergone arthrocentesis were included. Tryptophan and kynurenine levels from synovial fluid were quantified by HPLC. Diagnostic value of kynurenine was evaluated and its effects on the proliferation of the chondrocyte cell line ATDC5 were determined. Synovial fluid kynurenine values from patients with septic arthritis (4.1,±,0.8,µmol/L, n,=,9) were significantly increased compared to patients with non-infectious inflammatory arthropathy (1.8,±,0.2,µmol/L, n,=,17) or osteoarthritis (1.2,±,0.1,µmol/L, n,=,15, p,<,0.01). At a cut-off value of 2.28,µmol/L kynurenine had a sensitivity of 0.89 and a specificity of 0.87. Further, kynurenine inhibited chondrocyte (ATDC5) cell proliferation in a dose-dependent manner. Septic arthritis is associated with significantly increased values of synovial kynurenine. Furthermore kynurenine inhibits proliferation of chondrocytes, which strongly suggests a pathophysiological effect of kynurenine on cartilage in inflammatory arthropathies. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1490,1496, 2010 [source] Wear, delamination, and fatigue resistance of melt-annealed highly crosslinked UHMWPE cruciate-retaining knee inserts under activities of daily livingJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 9 2010Oludele O. Popoola Abstract The wear, delamination, and fatigue resistance of artificially aged gamma irradiation-sterilized conventional polyethylene (CPE) and gas-plasma-sterilized melt-annealed highly crosslinked polyethylene tibial inserts (HXPE) were compared. Six CPE and 12 HXPE (six irradiated at 58,kGy and six at 72,kGy) left knee inserts were wear tested for 5.5 million cycles (Mc) under loads and motions that mimic activities of daily living, such as walking, chair rise, stair ascent, and deep squatting. Another six HXPE (72,kGy) and six CPE inserts were also tested under conditions that could produce severe delamination for 8 Mc. Ten other knees (five 72,kGy HXPE and five CPE) were subjected to posterior edge loading fatigue testing for 5 Mc. The HXPE inserts had an average wear rate reduction of about 80% relative to their CPE counterparts during all activities. All of the CPE inserts delaminated and fractured during high cycle deep squat (152° flexion) motions, while all the HXPE remained intact. None of the HXPE inserts delaminated after 8 Mc, while all of the CPE inserts developed delamination damage within 1.5,5.8 Mc of delamination testing. All CPE inserts developed subsurface cracks and delamination within 2.8 Mc during posterior edge loading fatigue studies, while none of the HXPE inserts showed cracking or delamination after 5 Mc. These results show that aged HXPE has higher wear and fatigue resistance than aged CPE, and offers potential long-term advantages for young active patients with sustained activities of daily living. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1120,1126, 2010 [source] Carboxy terminus of secreted phosphoprotein-24 kDa (spp24) is essential for full inhibition of BMP-2 activityJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 9 2010Elsa J. Brochmann Abstract Secreted phosphoprotein-24,kDa (spp24) is a bone morphogenetic protein (BMP)-binding protein isolated from bone. It exists in a number of size forms and is hypothesized to function as a BMP latency protein and/or a "slow release" mechanism for BMPs involved in bone turnover and repair. We have examined the hypothesis that proteolytic modification of the C-terminus of spp24 affects its BMP-2,binding properties and bioactivity in the BMP-2,stimulated ectopic bone forming bioassay. Three different size forms of recombinant spp24 that correspond to predicted 18.1,kDa, 16.0,kDa, and 14.5,kDa proteolytic products were compared to full-length (fl) spp24. One of these forms (spp18.1) we hypothesize to be the protein which Urist initially, but apparently inaccurately, called "BMP." Only full-length spp24 completely inhibited BMP-2,induced bone formation. The 18.1,kDa truncated isoform of spp24 which we hypothesize to be Urist's protein did not. The inhibitory capacity of the proteins was correlated with their kinetic constants, assessed by surface plasmon resonance. At the highest, inhibitory, dose of spp24 and its derivatives, kd ("stability") best predicted the extent of ectopic bone formation whereas at the lowest dose, which was not inhibitory, ka ("recognition") best predicted the extent of ectopic bone formation. We conclude that proteolytic processing of spp24 affects the interaction of this protein with BMP-2 and this affects the function of the protein. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1200,1207, 2010 [source] In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells,JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 9 2010Songlin Peng Abstract In vitro studies have demonstrated that strontium (Sr) could increase osteogenic differentiation of bone marrow stromal cells (BMSCs). We investigated the in vivo effect of Sr on BMSCs. Thirty-six female rats were randomly divided into the following groups: sham operated and treated with either vehicle (Sham,+,Veh) or Sr compound (Sham,+,Sr) and ovariectomized and treated with either vehicle (OVX,+,Veh) or Sr compound (OVX,+,Sr). Vehicle and Sr were orally administrated daily starting immediately after the surgery and continuing for 12 weeks. The anabolic effect of Sr on trabecular bone was determined at the structural and tissue level by microCT and histomorphometry, respectively. Colony formation assays demonstrated that BMSCs exhibited higher osteogenic colony but lower adipogenic colony in Sr-treated versus Veh-treated OVX rats. The mRNA level of osteogenic genes was higher, while the mRNA level of adipogenic genes was lower in BMSCs from Sr-treated versus Veh-treated Sham and OVX rats. The effect of Sr on rat BMSCs was reproducible in human BMSCs. Taken together, this study suggests that the anabolic effect of Sr on normal or osteoporotic bones is associated with increased osteoblastic differentiation of BMSCs. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1208,1214, 2010 [source] Influence of bone density on the cement fixation of femoral hip resurfacing componentsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 8 2010Rudi G. Bitsch Abstract In clinical outcome studies, small component sizes, female gender, femoral shape, focal bone defects, bad bone quality, and biomechanics have been associated with failures of resurfacing arthroplasties. We used a well-established experimental setup and human bone specimens to analyze the effects of bone density on cement fixation of femoral hip resurfacing components. Thirty-one fresh frozen femora were prepared for resurfacing using the original instruments. ASRÔ resurfacing prostheses were implanted after dual-energy X-ray densitometer scans. Real-time measurements of pressure and temperature during implantation, analyses of cement penetration, and measurements of micro motions under torque application were performed. The associations of bone density and measurement data were examined calculating regression lines and multiple correlation coefficients; acceptability was tested with ANOVA. We found significant relations between bone density and micro motion, cement penetration, cement mantle thickness, cement pressure, and interface temperature. Mean bone density of the femora was 0.82,±,0.13,g/cm2, t- score was ,0.7,±,1.0, and mean micro motion between bone and femoral resurfacing component was 17.5,±,9.1,µm/Nm. The regression line between bone density and micro motion was equal to ,56.7,×, bone density,+,63.8, R,=,0.815 (p,<,0.001). Bone density scans are most helpful for patient selection in hip resurfacing, and a better bone quality leads to higher initial component stability. A sophisticated cementing technique is recommended to avoid vigorous impaction and incomplete seating, since increasing bone density also results in higher cement pressures, lower cement penetration, lower interface temperatures, and thicker cement mantles. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:986,991, 2010 [source] Cefazolin embedded biodegradable polypeptide nanofilms promising for infection prevention: A preliminary study on cell responsesJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 8 2010Hongshuai Li Abstract Implant-associated infection is a serious complication in orthopedic surgery, and endowing implant surfaces with antibacterial properties could be one of the most promising approaches for preventing such infection. In this study, we developed cefazolin loaded biodegradable polypeptide multilayer nanofilms on orthopedic implants. We found that the amount of cefazolin released could be tuned. A high local concentration of cefazolin was achieved within the first a few hours and therefore may inhibit bacterial colonization in the critical postimplantation period. The developed cefazolin loaded nanofilms showed their in vitro efficacy against Staphylococcus aureus; the more antibiotics loaded, the longer the nanocoated implant had antibacterial properties. More interestingly, antibiotic-loaded polypeptide multilayer nanofilms also improved osteoblast bioactivity including cell viability and proliferation. These findings suggested that biodegradable polypeptide multilayer nanofilms as antibiotic carriers at the implant/tissue interface are compatible with human cells such as osteoblasts and bactericidal to bacteria such as S. aureus. These characteristics could be promising for preventing implant-associated infection and potentially improving bone healing. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:992,999, 2010 [source] Failure of xenoimplantation using porcine synovium-derived stem cell-based cartilage tissue constructs for the repair of rabbit osteochondral defectsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 8 2010Ming Pei Abstract The use of xenogeneic tissues offers many advantages with respect to availability, quality control, and timing of tissue harvest. Our previous study indicated that implantation of premature tissue constructs from allogeneic synovium-derived stem cells (SDSCs) facilitated cartilage tissue regeneration. The present study investigated the feasibility of xenoimplantation of SDSC-based premature tissue constructs for the repair of osteochondral defects. Porcine SDSCs were mixed with fibrin gel, seeded in polyglycolic acid (PGA) scaffolds, and cultured in a rotating bioreactor system supplemented for 1 month with growth factor cocktails. The engineered porcine premature tissues were implanted to repair surgically induced osteochondral defects in the medial femoral condyles of 12 rabbits. Three weeks after surgery, the xenoimplantation group exhibited a smooth, whitish surface while the untreated control remained empty. Surprisingly, 6 months after surgery, the xenoimplantation group displayed some tissue loss while the untreated control group was overgrown with fibrocartilage tissue. In the xenoimplantation group, chronic inflammation was observed in synovial tissue where porcine major histocompatibility complex (MHC) class II antigen positively stained in the engulfed foreign bodies. In addition, porcine source cells also migrated from the implantation site and may have been responsible for the observed loss of glycosaminoglycans (GAGs) underneath surrounding articular cartilage. The histological score was much worse in the xenoimplanted group than in the untreated control. Our study suggested that SDSC-based xenogeneic tissue constructs might cause delayed immune rejection. Xenotransplantation may not be an appropriate approach to repair osteochondral defects. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1064,1070, 2010 [source] Effect of pro-inflammatory and immunoregulatory cytokines on human tenocytesJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 8 2010Thilo John Abstract Tendon injury induces a local inflammatory response, characterized by the induction of pro-inflammatory cytokines. The aim of the present study was to analyze the effects of TNF,, IL-6 and IL-10 on key parameters of tendon homeostasis. Cultured primary human tenocytes were treated with the recombinant cytokines IL-6, IL-10, TNF,, or combinations of TNF, with IL-6 and IL-10 (10 ng/mL, 6, 24 h). Expression of type I collagen, elastin, MMP-1, TNF,, IL-1,, IL-6, IL-10, and suppressors of cytokine signaling (SOCS1, 3) was analyzed with the use of RTD-PCR, immunocytochemistry, and Western blot analysis. In response to TNF,, tenocytes reduced their type I collagen deposition but increased their elastin gene expression and highly upregulated their expression for MMP-1, pro-inflammatory (TNF,, IL-1,) and immunoregulatory (IL-6, IL-10) cytokines. TNF, stimulation augmented SOCS1, whereas SOCS3 expression in tenocytes was also induced by IL-6. The treatment of tenocytes with IL-6 and IL-10 had no effect on cytokine expression. Neither IL-6 nor IL-10 modulated the observed effects of TNF, significantly. These results indicate that TNF, strongly activates the tenocytes to amplify their own TNF, expression and, subsequently, that of other regulatory cytokines and matrix degrading enzymes. However, the impact of IL-6 and IL-10 on tenocytes remains unclear. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1071,1077, 2010 [source] Effect of glenohumeral abduction angle on the mechanical interaction between the supraspinatus and infraspinatus tendons for the intact, partial-thickness torn, and repaired supraspinatus tendon conditionsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 7 2010Nelly Andarawis-Puri Abstract Rotator cuff tears are difficult to manage because of the structural and mechanical inhomogeneity of the supraspinatus tendon. Previously, we showed that with the arm at the side, the supraspinatus and infraspinatus tendons mechanically interact such that conditions that increase supraspinatus tendon strain, such as load or full-thickness tears, also increase infraspinatus tendon strain. This suggests that the infraspinatus tendon may shield the supraspinatus tendon from further injury while becoming at increased risk of injury itself. In this study, the effect of glenohumeral abduction angle on the interaction between the two tendons was evaluated for supraspinatus tendon partial-thickness tears and two repair techniques. Principal strains were quantified in both tendons for 0°, 30°, and 60° of glenohumeral abduction. Results showed that interaction between the two tendons is interrupted by an increase in abduction angle for all supraspinatus tendon conditions evaluated. Infraspinatus tendon strain was lower at 30° and 60° than at 0° abduction angle. In conclusion, interaction between the supraspinatus and infraspinatus tendons is interrupted with increase in abduction angle. Additionally, 30° abduction should be further evaluated for management of rotator cuff tears and repairs as it is the angle at which both supraspinatus and infraspinatus tendon strain is decreased. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:846,851, 2010 [source] Compression therapy promotes proliferative repair during rat Achilles tendon immobilizationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 7 2010Nikos Schizas Abstract Achilles tendon ruptures are treated with an initial period of immobilization, which obstructs the healing process partly by a reduction of blood circulation. Intermittent pneumatic compression (IPC) has been proposed to enhance tendon repair by stimulation of blood flow. We hypothesized that daily IPC treatment can counteract the deficits caused by 2 weeks of immobilization post tendon rupture. Forty-eight Sprague-Dawley SD) rats, all subjected to blunt Achilles tendon transection, were divided in three equal groups. Group A was allowed free cage activity, whereas groups B,C were immobilized at the operated hindleg. Group C received daily IPC treatment. Two weeks postrupture the rats were euthanatized and the tendons analyzed with tensile testing and histological assessments of collagen organization and collagen III-LI occurrence. Immobilization significantly reduced maximum force, energy uptake, stiffness, tendon length, transverse area, stress, organized collagen diameter and collagen III-LI occurrence by respectively 80, 75, 77, 22, 47, 65, 49, and 83% compared to free mobilization. IPC treatment improved maximum force 65%, energy 168%, organized collagen diameter 50%, tendon length 25%, and collagen III-LI occurrence 150% compared to immobilization only. The results confirm that immobilization impairs healing after tendon rupture and furthermore demonstrate that IPC-treatment can enhance proliferative tendon repair by counteracting biomechanical and morphological deficits caused by immobilization. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:852,858, 2010 [source] Improved bioengineered cartilage tissue formation following cyclic compression is dependent on upregulation of MT1-MMPJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 7 2010J. N. Amrith De Croos Abstract The generation of bioengineered cartilage tissue suitable for transplantation is a potential therapy to treat damaged cartilage. We have shown previously that the physical and biomechanical properties of bioengineered cartilage can be improved by the application of 30,min of cyclic compression by a mechanism involving sequential upregulation of gene and protein levels of membrane type-1 matrix metalloproteinase (MT1-MMP) and MMP-13. In the current study, we demonstrated that MT1-MMP is critical to this response, as blocking the upregulation of MT1-MMP prevented the improvement in tissue formation. MT1-MMP seems to act by inducing tissue remodeling as evidenced by the presence of aggrecan degradation products by Western blot analysis and increased release of matrix molecules into the media. Release of these molecules was diminished when MT1-MMP upregulation was prevented. This matrix degradation was likely due to MT1-MMP, as under conditions where MMP-13 expression is maintained (stimulation in the presence of MT1-MMP siRNA) the release of these matrix molecules into the media was still prevented. It also appears that MT1-MMP does not regulate MMP-13 gene expression, as MT1-MMP-siRNA pretreatment had no effect on MMP-13 expression following mechanical stimulation. Further analysis of the anabolic genes and proteins involved in mechanically stimulated cartilage will lead to better understanding of the mechanism(s) underlying tissue formation yielding improved bioengineered cartilage. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:921,927, 2010 [source] Modulation of Wnt signaling influences fracture repairJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 7 2010David E. Komatsu Abstract While the importance of Wnt signaling in skeletal development and homeostasis is well documented, little is known regarding its function in fracture repair. We hypothesized that activation and inactivation of Wnt signaling would enhance and impair fracture repair, respectively. Femoral fractures were generated in Lrp5 knockout mice (Lrp5,/,) and wild-type littermates (Lrp5+/+), as well as C57BL/6 mice. Lrp5,/, and Lrp5+/+ mice were untreated, while C57BL/6 mice were treated 2×/week with vehicle or anti-Dkk1 antibodies (Dkk1 Ab) initiated immediately postoperatively (Day 0) or 4 days postoperatively (Day 4). Fractures were radiographed weekly until sacrifice at day 28, followed by DXA, pQCT, and biomechanical analyses. Lrp5,/, mice showed impaired repair compared to Lrp5+/+ mice, as evidenced by reduced callus area, BMC, BMD, and biomechanical properties. The effects of Dkk1 Ab treatment depended on the timing of initiation. Day 0 initiation enhanced repair, with significant gains seen for callus area, BMC, BMD, and biomechanical properties, whereas Day 4 initiation had no effect. These results validated our hypothesis that Wnt signaling influences fracture repair, with prompt activation enhancing repair and inactivation impairing it. Furthermore, these data suggest that activation of Wnt signaling during fracture repair may have clinical utility in facilitating fracture repair. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:928,936, 2010 [source] Supraspinatus tendon repair into a bony trough in the rabbit: Mechanical restoration and correlative imagingJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2010Guy Trudel Abstract Recurrence of tears is a common complication after rotator cuff surgery. Retearing seems to occur early after surgery and may be attributed to too early or too vigorous exercises. We found no experimental data correlating the strength of the rotator cuff early after surgery and imaging. Our objectives were to measure the peak load to failure of rabbit supraspinatus tendon,bone constructs at early times postoperatively, to determine their mode of failure, and to determine whether computed tomography (CT) can predict their strength. We divided one supraspinatus tendon of 40 adult female white New Zealand rabbits and, after resection of the enthesis, sutured the tendon into a bony trough. Ten rabbits were killed immediately and 10 each at 1, 2, and 6 weeks postoperatively. The explanted tendons of both shoulders were imaged on CT and tested to failure. Compared to normal tendons (mean 210,±,42 N), the mean strength was very low at 0 weeks (57,±,21 N) and 1 week (86,±,33 N) (both p,<,0.05); it had recovered by 6 weeks (324,±,66 N). Early on, suture pullout was the most common mode of failure, whereas at 6 weeks, mid-substance tears predominated (p,<,0.05). Hypoattenuation on CT was associated with increased strength of the tendon,bone construct (p,<,0.05). The strength of the surgical construct is very low in the early postoperative period. Therefore, the shoulder should be submitted only to loads not interfering with healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:710,715, 2010 [source] Chondrogenic differentiation and lubricin expression of caprine infraspinatus tendon cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2010Tadanao Funakoshi Abstract Reparative strategies for the treatment of injuries to tendons, including those of the rotator cuff of the shoulder, need to address the formation of the cartilage which serves as the attachment apparatus to bone and which forms at regions undergoing compressive loading. Moreover, recent work indicates that cells employed for rotator cuff repair may need to synthesize a lubricating glycoprotein, lubricin, which has recently been found to play a role in tendon tribology. The objective of the present study was to investigate the chondrogenic differentiation and lubricin expression of caprine infraspinatus tendon cells in monolayer and three-dimensional culture, and to compare the behavior with bone marrow-derived mesenchymal stem cells (MSCs). The results demonstrated that while tendon cells in various media, including chondrogenic medium, expressed lubricin, virtually none of the MSCs synthesized this important lubricating molecule. Also of interest was that the cartilage formation capacity of the tendon cells grown in pellet culture in chondrogenic medium was comparable with MSCs. These data inform the use of tendon cells for rotator cuff repair, including for fibrocartilaginous zones. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:716,725, 2010 [source] BMP-7,induced ectopic bone formation and fracture healing is impaired by systemic NSAID application in C57BL/6-mice,JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2010Alexander S. Spiro Abstract Nonsteroidal antiinflammatory drugs (NSAIDs) are known to potentially impair the fracture healing process. The aim of the present study was to determine if the impairment of bone healing by systemic NSAID application is, at least in part, due to an interaction of NSAIDs with the bone anabolic BMP-7 pathway. Therefore, we first analyzed fracture healing in control and diclofenac-treated mice, where we not only found a significant impairment of fracture healing due to diclofenac treatment as assessed by biomechanical testing and µCT imaging, but also found high coexpression of bone morphogenetic protein-7 (BMP-7) and cyclooxygenase-2 (COX-2) within the fracture callus of both groups. To experimentally address the possible interaction between BMP-7 and COX-2, we then induced ectopic bone formation in control (n,=,10) and diclofenac-treated mice (n,=,10) by application of BMP-7 (recombinant human OP-1, rhOP-1) into the hamstring muscles. After 20 days of treatment, each ectopic bone nodule was analyzed by contact-radiography, µCT, histology, and histomorphometry. Diclofenac application decreased the trabecular number and bone mass in the ectopic bone nodules significantly due to reduced osteoblast number and activity. These data demonstrate that the bone anabolic effect of BMP-7 and fracture healing is impaired by diclofenac application, and suggest that the potential negative impact of NSAIDs on fracture healing is, at least in part, due to interference with BMP-7 signaling. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:785,791, 2010 [source] Platelet-rich plasma impairs osteoclast generation from human precursors of peripheral bloodJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2010Elisabetta Cenni Abstract Platelet-rich plasma is used to accelerate bone repair for the release of osteogenic growth factors from activated platelets. To date, the effects on osteoclasts have been only scarcely investigated, even though these cells are crucial for bone remodeling. The aim of this research was the evaluation of the effects of thrombin-activated platelets (PRP) on osteoclastogenesis from human blood precursors. We evaluated both the ability to influence osteoclast differentiation induced by the receptor activator of nuclear factor-kappaB ligand (RANKL), and the ability to induce osteoclast differentiation without RANKL. In both assays, the incubation with PRP supernatant at 10% did not significantly affect the formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells that were able to form the F-actin ring. However, when PRP at 25 and 50% was added to the medium without RANKL, the generation of TRACP-positive multinucleated cells was inhibited. PRP, even at 10%, reduced the osteoclast-mediated bone collagen degradation, suggesting inhibition of osteoclast activation. Similarly, after incubation with PRP supernatant, calcitonin receptor mRNA was lower than the untreated samples. In conclusion, PRP at 10% interfered with the complete differentiation process of human osteoclast precursors. At higher concentration it impaired osteoclast formation also at an early stage of differentiation. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:792,797, 2010 [source] Computational assessment of the effect of polyethylene wear rate, mantle thickness, and porosity on the mechanical failure of the acetabular cement mantleJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2010Oliver J. Coultrup Abstract Clinical studies have revealed that aseptic loosening is the dominant cause of failure in total hip arthroplasty, particularly for the acetabular component. For a cemented polyethylene cup, failure is generally accompanied by the formation of fibrous tissue at the cement,bone interface. A variety of reasons for the formation of this tissue have been suggested, including osteolysis and mechanical overload at the cement,bone interface. In this study, a computational cement damage accumulation method was used to investigate the effect of polyethylene cup penetration, cement mantle thickness, and cement porosity on the number of cycles required to achieve mechanical fatigue failure of the cement mantle. Cup penetration was found to increase cement mantle stresses, resulting in a reduction in cement mantle fatigue life of 9% to 11% for a high cup penetration rate. The effect of using a thin (2 mm) over a thick (4 mm) cement mantle also reduced cement mantle fatigue life between 9% and 11%, and greatly raised cancellous bone stresses. Cement porosity was found to have very little effect on cement mantle fatigue life. Failure modes and cement stresses involved suggest that only extreme combinations of a thin cement mantle and high cup penetration may lead to mechanical failure of the cement mantle, thereby allowing wear debris access to the cement,bone interface. A thin cement mantle may also lead to the mechanical overload of the cement,bone interface. In this manner, the authors suggest that the mechanical factors may contribute to the failure mode of cemented polyethylene cups. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:565,570, 2010 [source] Polymethylmethacrylate particles impair osteoprogenitor viability and expression of osteogenic transcription factors Runx2, osterix, and Dlx5JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2010Richard Chiu Abstract Polymethylmethacrylate (PMMA) particles have been shown to inhibit the differentiation of osteoprogenitor cells, but the mechanism of this inhibitory effect has not been investigated. We hypothesize that the inhibitory effects of PMMA particles involve impairment of osteoprogenitor viability and direct inhibition of transcription factors that regulate osteogenesis. We challenged MC3T3-E1 osteoprogenitors with PMMA particles and examined the effects of these materials on osteoprogenitor viability and expression of transcription factors Runx2, osterix, Dlx5, and Msx2. MC3T3-E1 cells treated with PMMA particles over a 72-h period showed a significant reduction in cell viability and proliferation as indicated by a dose- and time-dependent increase in supernatant levels of lactate dehydrogenase, an intracellular enzyme released from dead cells, a dose-dependent decrease in cell number and BrdU uptake, and the presence of large numbers of positively labeled Annexin V-stained cells. The absence of apoptotic cells on TUNEL assay indicated that cell death occurred by necrosis, not apoptosis. MC3T3-E1 cells challenged with PMMA particles during the first 6 days of differentiation in osteogenic medium showed a significant dose-dependent decrease in the RNA expression of Runx2, osterix, and Dlx5 on all days of measurement, while the RNA expression of Msx2, an antagonist of Dlx5-induced osteogenesis, remained relatively unaffected. These results indicate that PMMA particles impair osteoprogenitor viability and inhibit the expression of transcription factors that promote osteoprogenitor differentiation. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:571,577, 2010 [source] Mechanobiological response of tendon stem cells: Implications of tendon homeostasis and pathogenesis of tendinopathyJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2010Jianying Zhang Abstract Tendons are constantly subjected to mechanical loading in vivo. Recently, stem cells were identified in human, mouse, and rabbit tendons, but the mechanobiological responses of tendon stem cells (TSCs) are still undefined. Using an in vitro system capable of mimicking in vivo loading conditions, it was determined that mechanical stretching increased TSC proliferation in a stretching magnitude-dependent manner. Moreover, low mechanical stretching at 4% ("clamp-to-clamp" engineering strain) promoted differentiation of TSCs into tenocytes, whereas large stretching at 8% induced differentiation of some TSCs into adipogenic, chondrogenic, and osteogenic lineages, as indicated by upregulated expression of marker genes for adipocytes, chondrocytes, and osteocytes. Thus, low mechanical stretching may be beneficial to tendons by enabling differentiation of TSCs into tenocytes to maintain tendon homeostasis. However, large mechanical loading may be detrimental, as it directs differentiation of TSCs into non-tenocytes in tendons, thus resulting in lipid accumulation, mucoid formation, and tissue calcification, which are typical features of tendinopathy at later stages. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:639,643, 2010 [source] The effect of skeletal maturity on the regenerative function of intrinsic ACL cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2010Ashley N. Mastrangelo Abstract Anterior cruciate ligament (ACL) injuries are an important clinical problem, particularly for adolescent patients. The effect of skeletal maturity on the potential for ACL healing is as yet unknown. In this study, we hypothesized that fibroblastic cells from the ACLs of skeletally immature animals would proliferate and migrate more quickly than cells from adolescent and adult animals. ACL tissue from skeletally immature, adolescent, and adult pigs and sheep were obtained and cells obtained using explant culture. Cell proliferation within a collagen,platelet scaffold was measured at days 2, 7, and 14 of culture using AM MTT assay. Cellular migration was measured at 4 and 24 h using a modified Boyden chamber assay, and cell outgrowth from the explants also measured at 1 week. ACL cells from skeletally immature animals had higher proliferation between 7 and 14 days (p,<,0.01 for all comparisons) and higher migration potential at all time points in both species (p,<,0.01 for all comparisons). ACL cells from skeletally immature animals have greater cellular proliferation and migration potential than cells from adolescent or adult animals. These experiments suggest that skeletal maturity may influence the biologic repair capacity of intrinsic ACL cells. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:644,651, 2010 [source] Replacement of the medial tibial plateau by a metallic implant in a goat modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2010Roel J.H. Custers Abstract The purposes of the present study were to explore the surgical possibilities for replacement of the medial tibial plateau by a metallic implant in a large animal model and to examine the implications for the opposing cartilage. In six goats, the medial tibial plateau of the right knee was replaced by a cobalt,chromium implant, using polymethylmethacrylate bone cement for fixation. The unoperated left knee served as a control. At 26 weeks after surgery, the animals were killed, and the joints evaluated macroscopically. Cartilage quality was analyzed macroscopically and histologically. Glycosaminoglycan content, synthesis, and release were measured in tissue and medium. All animals were able to move and load the knees without any limitations. Macroscopic articular evaluation scores showed worsening 26 weeks after inserting the implant (p,<,0.05). Macroscopic and histologic scores showed more cartilage degeneration of the opposing medial femoral condyle in the experimental knee compared to the control knee (p,<,0.05). Higher glycosaminoglycan synthesis was measured at the medial femoral condyle cartilage in the experimental knees (p,<,0.05). This study shows that the medial tibial plateau can be successfully replaced by a cobalt,chromium implant in a large animal model. However, considerable femoral cartilage degeneration of the medial femoral condyle was induced, suggesting that care must be taken introducing hemiarthroplasty devices in a human clinical setting for the treatment of postmeniscectomy cartilage degeneration of the medial tibial plateau. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:429,435, 2010 [source] Wear mechanisms in metal-on-metal bearings: The importance of tribochemical reaction layersJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2010Markus A. Wimmer Abstract Metal-on-metal (MoM) bearings are at the forefront in hip resurfacing arthroplasty. Because of their good wear characteristics and design flexibility, MoM bearings are gaining wider acceptance with market share reaching nearly 10% worldwide. However, concerns remain regarding potential detrimental effects of metal particulates and ion release. Growing evidence is emerging that the local cell response is related to the amount of debris generated by these bearing couples. Thus, an urgent clinical need exists to delineate the mechanisms of debris generation to further reduce wear and its adverse effects. In this study, we investigated the microstructural and chemical composition of the tribochemical reaction layers forming at the contacting surfaces of metallic bearings during sliding motion. Using X-ray photoelectron spectroscopy and transmission electron microscopy with coupled energy dispersive X-ray and electron energy loss spectroscopy, we found that the tribolayers are nanocrystalline in structure, and that they incorporate organic material stemming from the synovial fluid. This process, which has been termed "mechanical mixing," changes the bearing surface of the uppermost 50 to 200 nm from pure metallic to an organic composite material. It hinders direct metal contact (thus preventing adhesion) and limits wear. This novel finding of a mechanically mixed zone of nanocrystalline metal and organic constituents provides the basis for understanding particle release and may help in identifying new strategies to reduce MoM wear. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:436,443, 2010 [source] Nanostructure of collagen fibrils in human nucleus pulposus and its correlation with macroscale tissue mechanicsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2010Darwesh M.K. Aladin Abstract Collagen fibrils are the main structural components of the nucleus pulposus tissue in the intervertebral discs. The structure,property relationship of the nucleus pulposus (NP) tissues is still unclear. We investigated the structure of individual collagen fibrils of the NP and evaluated its correlation with the bulk mechanical properties of the tissue. Collagen fibrils were extracted from the NP of discs retrieved from adolescents during scoliosis correction surgery, and the extracts were confirmed by SDS-PAGE. The diameters of the individual collagen fibrils were measured through atomic force microscopy, and the compressive mechanical properties of the tissues were evaluated by confined compression. The correlations between the nanoscale morphology of the collagen fibrils and the macroscale mechanical properties of the tissues were evaluated by linear regression. The SDS-PAGE results showed that the fibril extracts were largely composed of type II collagen. The mean diameter of the collagen fibrils was 92.1,±,26.54 nm; the mean swelling pressure and compressive modulus of the tissues were 6.15,±,4.3 kPa and 1.23,±,0.7 MPa, respectively. The mean fibril diameter had no linear correlation (R2,=,0.30) with the swelling pressure of the tissues. However, it had a mild linear correlation with the compressive modulus (p,=,0.023, R2,=,0.68). This is the first study, to our knowledge, to evaluate the nanostructure of the individual collagen fibrils of the nucleus pulposus and its relationship with macroscale mechanical properties of the NP tissues. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:497,502, 2010 [source] Effects of cyclic dynamic tensile strain on previously compressed inner annulus fibrosus and nucleus pulposus cells of human intervertebral disc,an in vitro studyJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2010Hwan Tak Hee Abstract Our objective was to investigate whether dynamic tensile strain on previously compressed human intervertebral disc (IVD) cells can restore the biosynthetic effects of collagen and glycosaminoglycan. Inner annulus fibrosus (AF) and nucleus pulposus (NP) tissues of adolescent idiopathic scoliosis cases undergoing thoracoscopic discectomy and fusion were cultured on compressive plates. Compressive stress was applied using 0.4 MPa at 1 Hz, for 2 h twice a day for 7 days, to the inner AF and NP tissues, followed by equibiaxial cyclic tensile strain to deform the released cells onto the plate's flexible bottom. With 10% elongation at a rate of 1 Hz, for 2 h twice a day for 7 days, a significant increase in the level of collagen and glycosaminoglycan of the previously compressed inner AF, as well as the level of glycosaminoglycan of the previously compressed NP cells were found. The DNA content and number of endoplasmic reticulum under transmission electron micrograph of the previously compressed inner AF and NP cell were also significantly increased. The results suggested that equibiaxial cyclic tensile strain at a rate of 1 Hz with 10% tensile strain was capable of increasing collagen and glycosaminoglycan synthesis of previously compressed inner AF cells, and glycosaminoglycan synthesis of previously compressed NP cells. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:503,509, 2010 [source] Novel Polysaccharide-derived hydrogel prevents perineural adhesions in a rat model of sciatic nerve adhesionJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2010Michiro Yamamoto Abstract We investigated the effects of a novel carboxymethylcellulose (CMC)-derived hydrogel, in which phosphatidylethanolamine (PE) was introduced into the carboxyl groups of CMC, for preventing perineural adhesion after extensive internal neurolysis of rat sciatic nerve. Sciatic nerves were randomly assigned to one of the following groups: the Control group, operated but no treatment; the HA group, operated and treated with 1% hyaluronan; the CMC,PE(L) group, operated and treated with low-viscosity CMC,PE hydrogel; and the CMC,PE(H) group, operated and treated with high-viscosity CMC,PE hydrogel. Perineural adhesions were evaluated at 6 weeks. Nerves were also subjected to biomechanical testing to assess ultimate breaking strength. Electrophysiological and wet muscle weight measurements were performed. Breaking strengths were significantly lower for the CMC,PE(L) group than for the Control and HA groups. Latency was significantly longer for the Control group than for the CMC,PE(L) group at 20 days. The mean percentage of wet muscle weight to body weight was significantly lower for the Control group than for the CMC,PE(L) group at 6 weeks. Low-viscosity CMC,PE hydrogel appears to prevent perineural adhesions and allow early restoration of nerve function. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:284,288, 2010 [source] Tendon-selective genes identified from rat and human musculoskeletal tissuesJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2010Scott A. Jelinsky Abstract Mesenchymal stems cells have a demonstrated ability to differentiate into muscle, bone, and fat. Determining whether these same cells have the ability to differentiate into tendon-like fibroblasts has been hampered by the lack of specific tendon cell marker genes. In order to identify molecular markers of mature tendon, expression profiling was used to identify genes expressed in adult rat and human tendon tissue compared to other musculoskeletal tissues. Using this technique, approximately 1,600 transcripts appeared to be selectively expressed in rat tendon tissue and approximately 300 transcripts appeared to be selectively expressed in human tendon tissue, with ,20 genes selectively expressed in both human and rat tendon tissue. Of these common tendon-selective genes, thrombospon-din-4 (THBS4) and tenomodulin (TNMD) were found to have the highest tendon-selective expression compared to other tissues examined. Interestingly, expression of these tendon-selective genes, which are present in primary tendon fibroblasts, is lost when these cells are placed in two-dimensional culture systems. In conclusion, this study has defined a set of tendon-selective genes present in both adult rat and human tendons. Identification of tendon-selective genes provides potential molecular tools to facilitate a better understanding of tendon development and tendon repair. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:289,297, 2010 [source] | ||||||||||