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Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_16 | Pages 54 - 54
1 Apr 2013
Cheng TL Valchev P Dehghani F Little DG Schindeler A
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Introduction. Bone tissue engineering approaches are an emerging strategy to treat bone defects, and commonly involve the delivery of osteogenic cells and/or drugs via a porous scaffold. We have been exploring an alternative injectable approach for drug delivery that would obviate the need for invasive surgery. Hypothesis. Sucrose Acetate Isobutyrate (SAIB) is a sucrose-based ester that is a highly viscous semi-solid. Diluting SAIB with 10–20% ethanol markedly reduces its viscosity, with ethanol diffusing rapidly after in vivo injection. This phase transitioning property makes SAIB an ideal candidate for bone tissue engineering. Materials and methods. The capacity of SAIB to act as a delivery system for recombinant human BMP-2 (rhBMP-2) was tested in a mouse ectopic bone formation model. In this model SAIB was used to deliver 0 to 10μg rhBMP-2. Next, SAIB was compared with porous collagen scaffold used clinically to delivery rhBMP-2 in a head-to-head trial. Commercial SAIB and SAIB produced in-house were also compared. Bone volumes were quantified by μCT. Discussion. Bone was found to form with as little as 2μg rhBMP-2 when delivered with SAIB. Injected SAIB also showed minimal inflammatory response and rapid breakdown, with bone formation occurring between one and two weeks. Conclusion. SAIB was found to be an effective delivery system for rhBMP-2 with translational utility. Future work will be required to examine the upscaling of this delivery system


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 401 - 401
1 Sep 2012
Aurégan J Bérot M Magoariec H Hoc T Bégué T Hannouche D Zadegan F Petite H Bensidhoum M
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Introduction. Osteoporosis is a metabolic disease of the bone responsible for a loss of bone resistance and an increase in fracture risk. World Health Organization (WHO) estimations are about 6.3 millions of femoral neck fractures in the world by 2050. These estimations make osteoporosis a real problem in term of public health. Knowledge in biological tissues mechanical behaviour and its evolution with age are important for the design of diagnosis and therapeutic tools. From the mechanical aspect, bone resistance is dependent on bone density, bone architecture and bone tissue quality. If the importance of bone density and bone architecture has been well explored, the bone tissue quality still remains unstudied because of the lack of biomechanical tools suitable for testing bone at this microscopic dimension. Therefore the goal of this study is to estimate the osteoporotic cancellous bone tissue mechanical behaviour at its microscopic scale, using an approach coupling mechanical assays and digital reconstruction. Materials and methods. The experimental study is based on cancellous bone tissue extracted from human femoral head. Forty 8mm diameters bone cylinders have been removed from femoral head explanted after a femoral neck fracture treated by arthroplasty. These cylinders have been submitted to a digitally controlled compressive trial. Before and after the trials, microscanner analyses with an 8 μm spatial resolution have been realized in order to determine the micro structural parameters. The cylinders have been rebuilt with the digital model-building in order to estimate the mechanical behaviour and the bone quality. Results. The results will be presented from a macroscopic and microscopic point of view and will show the relationship between gender and age of the patients. At the macroscopic scale, we will look at that apparent young modulus heterogeneity and the cracking strength. At the microscopic scale, we will confirm that the cancellous bone tissue mechanical behaviour is close to the Haversian bone tissue mechanical behaviour. Finally, the parametric study will permit us to point out the main microstructural components influencing cancellous bone tissue quality. Conclusion. This study allows a precise estimation of the osteoporotic cancellous bone tissue mechanical behaviour. It seems to be a great step in the understanding of this disease and it could probably lead to great improvements in the diagnosis, prognostic, medical and surgical approaches of osteoporosis


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_16 | Pages 89 - 89
1 Apr 2013
Matsuki H Shibano J Nakatsuchi Y Kobayashi M Moriizumi T Kato H
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The ratio of the incidence of trochanteric to cervical fractures increased with age in the elderly female population, but the reason for this fact remain unclear. The purposes of this study were to investigate whether or not there are specificities of the local distribution of mechanical properties at the trochanteric region of the elderly female using a scanning acoustic microscope (SAM). Human proximal femurs were harvested from seven female cadavers (67–88 years) and proximal femur was coronally sectioned into halves across the center of neck. The surface of the coronal section was polished in order to achieve flat surfaces of smoothness well below the surface resolution in scanning with SAM. Bone tissue density and elastic modulus were calculated from the acquired SAM data. Mechanical properties were measured at the lateral and medial trochanter. Cortical bone tissue of the lateral trochanter had significantly lower elastic modulus than that of the medial trochanter in the all specimen over 70s(p<0.05). Trabecular bone tissue of proximal region of the lateral trochanter had significantly lower elastic modulus than that of distal region in all 80s specimens (p<0.05). Decrease of the elastic modulus of cortical bone in the lateral trochanter and low value of the elastic modulus of trabecular bone in the proximal region of the lateral trochanter may be related to the increase of the ratio of trochanteric to cervical fractures with age in the elderly female population


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 510 - 516
1 Apr 2011
Sugata Y Sotome S Yuasa M Hirano M Shinomiya K Okawa A

Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks. In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 197 - 197
1 Sep 2012
Benazzo F Gastaldi G Fontana J Marullo M
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Engineered bone tissue to recreate the continuity of damaged skeletal segments is one of the field of interest of tissue engineering. Trabecular titanium has very good mechanical properties and high in vitro and in vivo biocompatibility: it can be used in biomedical applications to promote osteointegration demonstrating that it can be successfully used for regenerative medicine in orthopaedic surgery (1). Purpose of this investigation was to evaluate the behavior of adipose tissue derived stem cells (hASCs) cultured on scaffolds of Trabecular TitaniumTM (Lima-Lto) (TT). hASCs are considered to be multipotent mesenchymal stem cells that are easily induced to differentiate into functional osteoblasts both in vitro and in vivo (2). The hASCs were obtained from the subcutaneous adipose tissue of healthy donors during total hip replacement procedures after digestion with collagenase. They were seeded on monolayer and on the TT scaffolds, and incubated at 37 degrees C in 5% CO2 with osteogenic medium or control medium. The expression of bone-related genes using RT-PCR, time course of alkaline phosphatase activity and morphological investigation with Scanning Electron Microscopy (SEM) were performed to evaluate the osteogenic differentiation of hASCs. Alkaline phosphatase activity, marker of the differentiation toward the osteogenic pattern, was significantly higher in hASCs grown with osteogenic medium than in cells grown with control medium, both in monolayer and TT scaffolds; moreover, also alkaline phosphatase of hASCs grown on TT scaffolds in the presence of control medium increased with time, differently from that of cells grown on monolayer. The osteogenic differentiated hASCs expressed the bone-related genes type I collagen, osteocalcin, Runx-2 and alkaline phosphatase. SEM observations showed that hASCs differentiated toward osteoblast-like cells: they produced a big amount of extracellular matrix that covered the surface of the porous scaffolds with bridges between the pore walls. These data suggest that hASCs are able to adhere to TT scaffolds, to acquire an osteoblastic phenotype and to produce abundant extracellular matrix, with but also without osteogenic medium. We can therefore conclude that this material carries osteinductive properties being responsible of ostegenic differentiation; consequently, this scaffold/cells construct is effective to regenerate damaged tissue and to restore the function of bone tissue


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 467 - 467
1 Sep 2012
Ding M Overgaard S
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Introduction. Osteoporosis (OP), osteoarthrosis (OA), and rheumatoid arthritis (RA) are the most common age-related degenerative bone diseases, and major public health problems in terms of enormous amount of economic cost. RA is considered as a major cause of secondary osteoporosis. At late stage, OP often leads to skeletal fractures, and OA and RA result in severe joint disability. Over the last a few decades, much significant research on the properties has been carried out on these diseases, however, a detailed comparison of the microarchitecture of cancellous bones of these diseases is not available. In this study, we investigated three-dimensional (3-D) microarchitectural properties of OP, OA and RA cancellous bone. We hypothesized that there were significant differences in microarchitecture among OP, OA and RA bone tissues that might lead to different bone quality. Materials and Method. Twenty OP, fifty OA, and twelve RA femur heads were harvested from patients undergone total hip replacement surgery. Cubic cancellous bone samples (8∗8∗8 mm3) were prepared and scanned with a high resolution microtomographic system (vivaCT 40, Scanco Medical AG., Brüttisellen, Switzerland). Then micro-CT images were segmented using individual thresholds to obtain accurate 3-D data sets. Detailed microarchitectural properties were evaluated based on novel unbiased, model-free 3-D methods. For statistical analysis, one-way ANOVA was used, and a p<0.05 was considered significant. Results. Significant differences in the microarchitecture of cancellous bone were observed among the OP, OA and RA groups. Compared with the other groups, OP cancellous bone had lowest density, thinner, typical rod-like structure and less connectivity (all p<0.01). Interestingly, there were no significant differences in the microarchitectural properties measured between the OA and RA cancellous bones. Both OA and RA cancellous bones had significant higher bone volume fraction and were thicker, typical plate-like structure compared with the OP group (all p<0.01), even though there was clearly bone erosion observed in RA cancellous bone. Discussion. Quantification of the alterations in bone properties and quality will help to gain more insights into the pathogenesis of degenerative bone diseases and to target and develop novel approaches for the intervention and treatment, and for the design, fixation and durability of total joint prosthesis. Our study demonstrated that there were significant differences in the microarchitecture of the OP, OA and RA femur head cancellous bone. The OA and RA cancellous bone had similar bone density and microarchitecture despite apparent bone erosion in the RA cancellous bone. These results from femur head did not support the traditional notion that RA and OP had similar low bone density. Thus, whether femur head bone tissues from these diseases have similar bone collagen, mineral and mechanical properties, more importantly bone quality, should be clarified in the future


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_33 | Pages 3 - 3
1 Sep 2013
Maclaine S Bennett A Gadegaard N Meek R Dalby M
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Nanoscale topography increases the bioactivity of a material and stimulates specific responses (third generation biomaterial properties) at the molecular level upon first generation (bioinert) or second generation (bioresorbable or bioactive) biomaterials. We developed a technique (based upon the effects of nanoscale topography) that facilitated the in vitro expansion of bone graft for subsequent implantation and investigated the optimal conditions for growing new mineralised bone in vitro. Two topographies (nanopits and nanoislands) were embossed into the bioresorbable polymer Polycaprolactone (PCL). Three dimensional cell culture was performed using double-sided embossing of substrates, seeding of both sides, and vertical positioning of substrates. The effect of Hydroxyapatite, and chemical stimulation were also examined. Human bone marrow was harvested from hip arthroplasty patients, the mesenchymal stem cells culture expanded and used for cellular analysis of substrate bioactivity. The cell line specificity and osteogenic behaviour was demonstrated through immunohistochemistry, confirmed by real-time PCR and quantitative PCR. Mineralisation was demonstrated using alizarin red staining. Results showed that the osteoinduction was optimally conferred by the presence of nanotopography, and also by the incorporation of hydroxyapatite (HA) into the PCL. The nanopit topography and HA were both superior to the use of BMP2 in the production of mineralised bone tissue. The protocol from shim production to bone marrow harvesting and vertical cell culture on nanoembossed HaPCL has been shown to be reproducible and potentially applicable to economical larger scale production


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 19 - 19
1 Sep 2012
Carrera E Marchetto A Reis F
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Introduction. The aim of this study is to present the results of the surgical treatment of the humeral neck fracture applying two different plates based on the presence or not of bone compression. Material and Methods. Thirty two patients with displced proximal humerus fracture were operated on between January 2002 and August 2007. After radiographic analysis, the fractures were classified into two types: non-compressive (without loss of bone tissue – not impacted fracture) and compressive (with permanent bone loss due to compression between the fragments – impacted valgus fracture) fractures. Depending on the presence or not of bone compression, two different plates were applied for osteosynthesis: a locking angled blade plate, for “non-compressive fractures” and a locking angled “spacer” plate, for “compressive fractures”. Results. Twenty (59%) fractures were considered “non-compressive” and operated on applying the locking angled blade plate, and 12 (41%) were classified as “compressive fractures” and were operated on applying a locking angled “spacer” plate. Conclusion. the displaced humeral neck fractures may or may not undergo compression and permanent deformity among the fragments. The displaced fractures should be treated in two different manners, depending on whether or not there is bone compression between the fragments


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_16 | Pages 18 - 18
1 Apr 2013
Augat P Betz V Schroeder C Goettlinger M Jansson V Mueller PE Betz OB
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Common cell based strategies for treating bone defects require time-consuming and expensive isolation and expansion of autologous cells. We developed a novel expedited technology creating gene activated muscle grafts. We hypothesized that BMP-2 activated muscle grafts provide healing capabilities comparable to autologous bone grafting, the clinical gold standard. Two male, syngeneic Fischer 344 rats served as tissue donors. Muscle tissue was harvested from hind limbs and incubated with an adenoviral vector carrying the cDNA encoding BMP-2. Bone tissue was harvested from the iliac crest. Segmental bone defects were created in the right femora of 12 rats and were filled with either BMP-2 activated muscle tissue or bone grafts. After 8 weeks, femora were evaluated by radiographs, microCT, and biomechanical tests. BMP-2 activated muscle grafts and autologous bone grafts resulted in complete mineralization and healing, as documented by radiographs and microCT. Bone volume in the muscle graft defects (33+/-12mm3) was similar to autologous bone graft defects (39+/-5mm3). Torque at failure of the two groups was statistically indistinguishable (240+/-115 Nmm vs. 232+/-108Nmm). In previous experiments we demonstrated that the large segmental defect model in this study will not heal with either empty defects or non-activated muscle grafts. Our findings therefore demonstrate that BMP-2 gene activation of muscle tissue effectively stimulates defect healing similar to autologous bone grafts


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 111 - 111
1 Sep 2012
Dallari D Del Piccolo N Savarino L Fantasia R Rani N Stagni C
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Introduction. We evaluated the osteogenic potential of a novel biomimetic bone paste (DBSint®), made of a combination of a human demineralized bone matrix (hDBM) and a nano-structured magnesium-enriched hydroxyapatite (Mg-HA), in a standardized clinical model of high tibial osteotomy for genu varus. Methods. A prospective, randomized, controlled study was performed and thirty patients were enrolled and assigned to three groups: DBSint® (Group I), nano-structured Mg-HA (SINTlife®) (Group II) and lyophilized-bone-chips (Group III). Six weeks after surgery, computed tomography-guided biopsies of the grafts were performed. Clinical/radiographic evaluation was performed at six weeks, twelve weeks, six months, one and 2 year after surgery, in order to verify if the graft type influenced the healing rate. Results. By histomorphometry, DBSint® was shown able to promote a quick and effective bone tissue regeneration, superior to the healing process occurred in presence of SINTlife® and lyophilized bone chips. At a mean follow up of 32,59 months, no statistical differences between the groups were found, both pre-and post-operatively, according to the Knee Society Scoring System. Mean time of ostointegration was 3,9 months in the DBSint® group, 4,2 months in the lyophilized-bone group and 4,5 in the SINTlife® group. Discussion/conclusion. Orthopedic practice may be adversely affected by an inadequate bone repair that might compromise the success of surgery. Therapy for bone regeneration with DBSint® could be particularly attractive in the treatment of patients with bone defects difficult to heal, where it could shorten the period necessary for bone regeneration, due to the higher osteogenetic potential


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 104 - 104
1 Sep 2012
Weinberg A Widni E Pichler K Seles M Manninger M Heidari N
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Injuries to growth plates may initiate the formation of reversible or irreversible bone-bridges, which may lead to partial or full closure of the growth plate resulting in bone length discrepancy, axis deviation or joint deformity. Blood vessels and vascular invasion are essential for the formation of new bone tissue. The aim of our study was to investigate the spatial and temporal expression VEGF and its receptors R1 and R2 as well as the ingrowth of vessels in the formation of bone bridges in a rat physeal injury model. Quantitative Real Time - Polymerase Chain Reaction (qRT-PCR) was performed for Vascular Endothelial Growth Factor (VEGF) and its R1 and R2 receptors. Samples from the proximal epiphysis, physis and metaphysis of the tibial bone were prepared for immunohistochemical analysis to demonstrate the spatial expression of VEGF and its R1 and R2 receptors as well as laminin. Kinetic expression of VEGF and VEGF-R1 mRNA documented a tendency towards an expression increase on day 7. Histological analysis showed a haematoma containing bone fragments on day 1which was replaced by a bony bridge by day 14. This remodelled and consolidated by day 82. These trabeculae were accompanied by vessel formation. Expression of VEGF was observed on the bone fragments and the haematoma from day 1 through to day 82. Although VEGF-R1 was expressed at all time points the expression of VEGF-R2 was noted until the 14th day. Physeal bone bridge formation is a combination of both enchondral and intramembranous ossification. This is in part triggered by the bony debris observed within the lesion in the first few days. By washing this debris out the likelihood of bone bridge formation may be reduced. We recommend this practice when operating on the physis in order to avoid iatrogenic physeal bar formation


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 496 - 496
1 Sep 2012
Huber M Zweymueller K Lintner F
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Background. Continual implant stability is an important factor for the long-term success of cementless hip replacements. The increasing lifespan of patients causes a higher frequency of osteoporosis which may result in implant loosening due to bone loss. This study aimed to evaluate stability of long living implants in patients with advanced age. Patients and methods. Nine cementless stems made of Titanium-alloy including adjacent bone tissue obtained post mortem were evaluated by radiologic-microradigraphical, histological and morphometrical analysis. The percentage of the surface area covered by bone (BICI=bone implant contact index) was determined. The age of seven women and two men ranged between 81 and 92 years. The time in situ ranged between 10 and 20 years. From the entire length of the femora bearing implants 5 transverse segments were excised, dehydrated, embedded in methylmethacrylate. After the grinding procedure, the sections were evaluated by light microscopy and morphometrical analysis. The autopsy findings were recorded. Atherosclerosis and their related diseases were evident in all cases. Results. The femora of all female patients revealed features of high bony atrophy with concomitant transformation of the corticalis into spongy bone, whereas in male patients minor to moderate atrophic bone changes in the proximal femoral area without implication of the corticalis could be observed. All of the cementless stems made of Titanium-alloy showed osteointegration. The stabilization of the implant resulted in the forceps-like encasement of the edges of the implant within the cortical anchoring and by the development of compensatory bony hypertrophy. The BICI ranged between 35 und 63 percent. Conclusion. Elderly patients provided with cementless hip replacments revealed stable implants in spite of marked bone atrophy and an implantation period up to 20 years. Simultaneously, severe atherosclerosis and their related diseases, which may contribute to bone loss, were evident. The present findings may result from the favoring properties of cementless endoprostheses made of titanium alloy, cortical prosthesis anchoring, and self regulating bone processes. Pharmacologic and therapeutic consequences together with geriatric assessment should be required to preserve functionality and mobility


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 10 | Pages 1347 - 1350
1 Oct 2006
Karn NK Singh GK Kumar P Shrestha B Singh MP Gowda MJ

We conducted a randomised controlled trial to compare external fixation of trochanteric fractures of the femur with the more costly option of the sliding hip screw. Patients in both groups were matched for age (mean 67 years, 50 to 100) and gender. We excluded all pathological fractures, patients presenting at more than one week, fractures with subtrochanteric extension or reverse obliquity, multiple fractures or any bone and joint disease interfering with rehabilitation. The interval between injury and operation, the duration of surgery, the amount of blood loss, the length of hospital stay and the cost of treatment were all significantly higher in the sliding hip screw group (p < 0.05). The time to union, range of movement, mean Harris hip scores and Western Ontario and McMaster University knee scores were comparable at six months. The number of patients showing shortening or malrotation was too small to show a significant difference between the groups. Pin-track infection occurred in 18 patients (60%) treated with external fixation, whereas there was a single case of wound infection (3.3%) in the sliding hip screw group.