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Introduction: Neck of femur fractures (NOF) in younger adults are often treated by head-preserving fixation procedures. Non-union is an infrequent but troublesome complication following internal fixation, especially in atypical presentations. Vascularized (VFG) and non-VFG (NVFG) fibular grafting and realignment procedures have been described as an adjunct to internal fixation. Reports are rare regarding the versatility of fibular grafts, their use, and their outcomes in the United Kingdom. Case Report: We present three complex NOF cases performed in the United Kingdom. One case is a 29-year-old Asian female treated with NVFG for a pathological transverse NOF fracture secondary to fibrous dysplasia. One case is a non-union following failed surgical management and revised using NVFG and dynamic hip screws. The last case is a VFG in a complex non-union intra-capsular fracture following conservative management in a 17-year-old male. Certain patient characteristics are described which make joint preserving surgery more attractive. All fractures united with no revisions at the time of final follow-up. Distinctions between the use of VFG and NVFG grafts are discussed. Conclusion: This case series demonstrates the important versatility of fibular grafting and how its properties are used in different cases. Fibular grafting is an effective technique in pathological, non-union, and late-presenting NOF. Both types of grafts introduce additional biology for difficult cases where neck resorption and adequate fixation are an issue, with NVFG grafts much easier to perform.
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BACKGROUND: Recent approaches have sought to harness the potential of stem cells to regenerate bone that is lost as a consequence of trauma or disease. Bone marrow aspirate (BMA) provides an autologous source of osteoprogenitors for such applications. However, previous studies indicated that the concentration of osteoprogenitors present in BMA is less than required for robust bone regeneration. We provide further evidence for the importance of BMA enrichment for skeletal tissue engineering strategies using a novel acoustic wave-facilitated filtration strategy to concentrate BMA for osteoprogenitors, clinically applicable for intraoperative orthopedic use. METHODS: Femoral BMA from 15 patients of an elderly cohort was concentrated for the nucleated cell fraction against erythrocytes and excess plasma volume via size exclusion filtration facilitated by acoustic agitation. The effect of aspirate concentration was assessed by assays for colony formation, flow cytometry, multilineage differentiation and scaffold seeding efficiency. RESULTS: BMA was filtered to achieve a mean 4.2-fold reduction in volume with a corresponding enrichment of viable and functional osteoprogenitors, indicated by flow cytometry and assays for colony formation. Enhanced osteogenic and chondrogenic differentiation was observed using concentrated aspirate and enhanced cell-seeding efficiency onto allogeneic bone graft as an effect of osteoprogenitor concentration relative specifically to the concentration of erythrocytes in the aspirate. CONCLUSIONS: These studies provide evidence for the importance of BMA nucleated cell concentration for both cell differentiation and cell seeding efficiency and demonstrate the potential of this approach for intraoperative application to enhance bone healing.
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Células de la Médula Ósea/citología , Diferenciación Celular , Células Madre Mesenquimatosas/citología , Osteogénesis , Anciano , Anciano de 80 o más Años , Células de la Médula Ósea/metabolismo , Regeneración Ósea/genética , Supervivencia Celular , Femenino , Filtración , Citometría de Flujo , Humanos , Masculino , Células Madre Mesenquimatosas/metabolismo , Persona de Mediana Edad , Ingeniería de TejidosRESUMEN
AIMS: The aim of this study was to compare open reduction and internal fixation (ORIF) with revision surgery for the surgical management of Unified Classification System (UCS) type B periprosthetic femoral fractures around cemented polished taper-slip femoral components following primary total hip arthroplasty (THA). METHODS: Data were collected for patients admitted to five UK centres. The primary outcome measure was the two-year reoperation rate. Secondary outcomes were time to surgery, transfusion requirements, critical care requirements, length of stay, two-year local complication rates, six-month systemic complication rates, and mortality rates. Comparisons were made by the form of treatment (ORIF vs revision) and UCS type (B1 vs B2/B3). Kaplan-Meier survival analysis was performed with two-year reoperation for any reason as the endpoint. RESULTS: A total of 317 periprosthetic fractures (in 317 patients) with a median follow-up of 3.6 years (interquartile range (IQR) 2.0 to 5.4) were included. The fractures were type B1 in 133 (42.0%), B2 in 170 (53.6%), and B3 in 14 patients (4.4%). ORIF was performed in 167 (52.7%) and revision in 150 patients (47.3%). The two-year reoperation rate (15.3% vs 7.2%; p = 0.021), time to surgery (4.0 days (IQR 2.0 to 7.0) vs 2.0 days (IQR 1.0 to 4.0); p < 0.001), transfusion requirements (55 patients (36.7%) vs 42 patients (25.1%); p = 0.026), critical care requirements (36 patients (24.0%) vs seven patients (4.2%); p < 0.001) and two-year local complication rates (26.7% vs 9.0%; p < 0.001) were significantly higher in the revision group. The two-year rate of survival was significantly higher for ORIF (91.9% (standard error (SE) 0.023%) vs 83.9% (SE 0.031%); p = 0.032) compared with revision. For B1 fractures, the two-year reoperation rate was significantly higher for revision compared with ORIF (29.4% vs 6.0%; p = 0.002) but this was similar for B2 and B3 fractures (9.8% vs 13.5%; p = 0.341). The most common indication for reoperation after revision was dislocation (12 patients; 8.0%). CONCLUSION: Revision surgery has higher reoperation rates, longer surgical waiting times, higher transfusion requirements, and higher critical care requirements than ORIF in the management of periprosthetic fractures around polished taper-slip femoral components after THA. ORIF is a safe option providing anatomical reconstruction is achievable.Cite this article: Bone Joint J 2023;105-B(2):124-134.
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Artroplastia de Reemplazo de Cadera , Fracturas del Fémur , Fracturas Periprotésicas , Humanos , Reoperación , Artroplastia de Reemplazo de Cadera/efectos adversos , Fracturas Periprotésicas/etiología , Fracturas Periprotésicas/cirugía , Fracturas del Fémur/etiología , Fracturas del Fémur/cirugía , FémurRESUMEN
CASE: A 26-year-old man presented with recurrent native hip dislocation after an initially traumatic posterior right hip dislocation. The combined soft-tissue and bony deficiency was addressed using an autologous bone block technique, as previously popularized for shoulder instability. Thirteen years postoperatively, no subsequent dislocations occurred, and the patient has an excellent functional outcome. CONCLUSION: The bone block technique for hip stabilization can be used to address focal acetabular deficiencies with promising long-term follow-up.
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Luxación de la Cadera , Luxaciones Articulares , Inestabilidad de la Articulación , Articulación del Hombro , Masculino , Humanos , Adulto , Luxación de la Cadera/complicaciones , Luxación de la Cadera/diagnóstico por imagen , Luxación de la Cadera/cirugía , Inestabilidad de la Articulación/cirugía , Articulación del Hombro/cirugía , Luxaciones Articulares/complicaciones , Acetábulo/diagnóstico por imagen , Acetábulo/cirugíaRESUMEN
BACKGROUND: This multicentre case-control study compares Vancouver Classification System (VCS) grade and Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) fracture type in interprosthetic femoral fractures (IPFFs) between primary total hip arthroplasty (THA) and ipsilateral total knee arthroplasty (TKA) to periprosthetic femoral fracture (PFF) without ipsilateral TKA. METHODS: Data were collected following institutional approval. Eighty-four IPFFs were assessed for VCS grade and AO/OTA type. Each IPFF case (84) was matched to five PFF controls (360) by age, gender and stem fixation philosophy (SMD<0.1). VCS grade and AO/OTA type were compared between the IPFF and PFF groups using weighted proportions and medians. RESULTS: Median (IQR) age of IPFF patients was 81.75 (76.57-85.33) years and 61 (72.6%) were female. The commonest VCS grade was B1 (34, 40.5%). The commonest AO/OTA type was spiral (51.8% of VCS B fractures; 50.0% of VCS C fractures). A greater proportion of fractures occurred distal to the stem in IPFF patients versus PFF patients (33.3% versus 18.2%, p = 0.003). VCS grade was significantly different between groups (p = 0.015). For VCS C fractures, twice as many AO/OTA transverse and wedge fractures occurred in the IPFF group compared to the PFF group (25.0% versus 12.6% and 7.1% versus 3.3%, respectively) although the overall difference was not statistically significant (p = 0.407). CONCLUSION: The presence of an ipsilateral TKA affects the location of PFF with more fractures occurring distal to the stem. A greater proportion of bending type fractures occurred when an ipsilateral TKA was present. These unstable fractures often require more complex surgery.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Fracturas del Fémur , Fracturas Periprotésicas , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Estudios de Casos y Controles , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/epidemiología , Fracturas del Fémur/cirugía , Fijación Interna de Fracturas , Humanos , Fracturas Periprotésicas/diagnóstico por imagen , Fracturas Periprotésicas/epidemiología , Fracturas Periprotésicas/cirugía , Reoperación , Estudios RetrospectivosRESUMEN
We report 3 patients who underwent total hip arthroplasty (THA) using large diameter metal-on-metal bearing. These patients initially presented with pain but went on to develop dislocation of the THA while awaiting investigations. Any pain following metal-on-metal bearing THA should be taken seriously and should trigger investigations to identify a metal reaction. If left untreated, these reactions can cause progressive soft tissue necrosis leading to instability. These patients should be considered for early revision of the bearing surface to prevent further soft tissue damage.
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Artroplastia de Reemplazo de Cadera/instrumentación , Luxación de la Cadera/etiología , Prótesis de Cadera/efectos adversos , Hipersensibilidad/complicaciones , Inestabilidad de la Articulación/etiología , Metales/efectos adversos , Osteoartritis de la Cadera/cirugía , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Cromo/sangre , Cobalto/sangre , Progresión de la Enfermedad , Femenino , Luxación de la Cadera/diagnóstico por imagen , Humanos , Inestabilidad de la Articulación/diagnóstico por imagen , Necrosis/etiología , Necrosis/patología , Radiografía , Reoperación , Traumatismos de los Tejidos Blandos/etiología , Traumatismos de los Tejidos Blandos/patologíaRESUMEN
Treatment of massive acetabular defects, both with and without pelvic discontinuity, is challenging. The implants utilized in the surgical procedure need to be stable and integrate with poor host bone stock. In the present study, we describe our experience addressing this challenge. METHODS: We identified all patients who underwent surgical implantation of a custom 3D-printed triflange prosthesis with dual-mobility bearings for the treatment of Paprosky 3B acetabular defects between 2014 and 2020. Operative, functional, and radiographic outcomes were assessed. RESULTS: A total of 19 patients were identified, including 11 women. The mean age was 77 years (range, 53 to 91 years), and 8 patients (42%) had proven or likely pelvic discontinuity. The mean follow-up was 53 months (range, 17 to 88 months; mode, 57 months). The cumulative implant survivorship was 100%. Two patients suffered notable sciatic nerve palsy, with 1 case being recurrent. There were no dislocations or fractures. The mean Oxford Hip Score improved significantly, from a mean of 8.6 (range, 0 to 22) preoperatively to 35 (range, 10 to 48) postoperatively (p < 0.0001). Radiographically, there was excellent correlation between implant position and the preoperative plan (p > 0.05). There were no cases of implant loosening or migration, which suggests that stabilization was achieved even among cases with pelvic discontinuity. CONCLUSIONS: These early results suggest that the use of a custom 3D-printed triflange implant has potential advantages over traditional constructs in the treatment of massive acetabular defects, with and without pelvic discontinuity. Excellent implant survivorship and functional improvement were demonstrated in this challenging patient cohort. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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Concerns over disease transmission, high costs and limited supply have led to interest in synthetic grafts in the field of impaction bone grafting (IBG). Poly(DL-lactic acid) (PLA) grafts are attractive alternatives due to their biocompatibility, established safety and versatile manufacturing process. This study examined the potential of PLA scaffolds augmented with human bone marrow stromal cells (HBMSCs) in IBG. In vitro and in vivo studies were performed on impacted morsellised PLA seeded with HBMSC and compared to PLA alone. In vitro samples were incubated under osteogenic conditions and in vivo samples were implanted subcutaneously into severely compromised immunodeficient mice, for 4 weeks. Biochemical, histological, mechanical and 3D micro-computed tomography analyses were performed. HBMSC viability, biochemical activity and histological evidence of osteogenic cellular differentiation, post-impaction were observed in vitro and in vivo in PLA/HBMSC samples compared to impacted PLA alone. In vitro PLA/HBMSC samples demonstrated evidence of mechanical enhancement over PLA alone. In vivo studies showed a significant increase in new bone and blood vessel formation in the PLA/HBMSC constructs compared to PLA alone. With alternatives to allograft being sought, these studies have demonstrated PLA/HBMSC living composites, to be a potential prospect as a biological bone graft extender for future use in the field of IBG.
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Materiales Biocompatibles/química , Células de la Médula Ósea/citología , Ácido Láctico/química , Poliésteres/química , Polímeros/química , Células del Estroma/citología , Fosfatasa Alcalina/metabolismo , Animales , Materiales Biocompatibles/farmacología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacología , Huesos/citología , Huesos/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Inmunohistoquímica , Ácido Láctico/farmacología , Masculino , Ratones , Ratones SCID , Poliésteres/farmacología , Polímeros/farmacología , Resistencia al Corte , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Ingeniería de Tejidos/métodosRESUMEN
Vibration is commonly used in civil engineering applications to efficiently compact aggregates. This study examined the effect of vibration and drainage on bone graft compaction and cement penetration in an in vitro femoral impaction bone grafting model with the use of 3-dimensional micro-computed tomographic imaging. Three regions were analyzed. In the middle and proximal femoral regions, there was a significant increase in the proportion of bone grafts with a reciprocal reduction in water and air in the vibration-assisted group (P < .01) as compared with the control group, suggesting tighter graft compaction. Cement volume was also significantly reduced in the middle region in the vibration-assisted group. No difference was observed in the distal region. This study demonstrates the value of vibration and drainage in bone graft compaction, with implications therein for clinical application and outcome.
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Trasplante Óseo/métodos , Drenaje , Fémur/cirugía , Vibración , Cementos para Huesos , Fuerza Compresiva , Fémur/diagnóstico por imagen , Humanos , Modelos Biológicos , Estrés Mecánico , Tomografía Computarizada por Rayos XRESUMEN
Despite technological advancements, further innovations in the field of orthopedics and bone regeneration are essential to meet the rising demands of an increasing aging population and associated issues of disease, injury and trauma. Nanotopography provides new opportunities for novel implant surface modifications and promises to deliver further improvements in implant performance. However, the technical complexities of nanotopography fabrication and surface analysis have precluded identification of the optimal surface features to trigger osteogenesis. We herein detail the osteoinductive potential of discrete nanodot and nanowire nanotopographies. We have examined the ability of modified titanium and titanium alloy (Ti64) surfaces to induce bone-specific gene activation and extracellular matrix protein expression in human skeletal stem cells (SSCs) in vitro, and de novo osteogenic response within a murine calvarial model in vivo. This study provides evidence of enhanced osteogenic response to nanowires 300 surface modifications, with important implications for clinical orthopedic application.
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Bone is a highly specialized connective tissue and has a rare quality as one of the few tissues that can repair without a scar to regain pre-injury structure and function. Despite the excellent healing capacity of bone, tumor, infection, trauma and surgery can lead to significant bone loss requiring skeletal augmentation. Bone loss in the lower limb poses a complex clinical problem, requiring reconstructive techniques to restore form and function. In the past, amputation may have been the only option; however, there is now an array of reconstructive possibilities and cellular therapies available to salvage a limb. In this review, we will evaluate current applications of bone tissue engineering techniques in limb reconstruction and identify potential strategies for future work.
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Enfermedades Óseas/terapia , Extremidad Inferior , Medicina Regenerativa/métodos , Medicina Regenerativa/tendencias , Animales , Enfermedades Óseas/metabolismo , Enfermedades Óseas/patología , Humanos , Ingeniería de Tejidos/métodos , Ingeniería de Tejidos/tendenciasRESUMEN
The healthcare socio-economic environment is irreversibly changing as a consequence of an increasing aging population, consequent functional impairment, and patient quality of life expectations. The increasing complexity of ensuing clinical scenarios compels a critical search for novel musculoskeletal regenerative and replacement strategies. While joint arthroplasty is a highly effective treatment for arthritis and osteoporosis, further innovation and refinement of uncemented implants are essential in order to improve implant integration and reduce implant revision rate. This is critical given financial restraints and the drive to improve cost-effectiveness and quality of life outcomes. Multi-scale modulation of implant surfaces, offers an innovative approach to enhancement in implant performance. In the current study, we have examined the potential of large area electron beam melting to alter the surface nanotopography in titanium alloy (Ti6Al4V). We evaluated the in vitro osteogenic response of human skeletal stem cells to the resultant nanotopography, providing evidence of the relationship between the biological response, particularly Collagen type I and Osteocalcin gene activation, and surface nanoroughness. The current studies demonstrate osteogenic gene induction and morphological cell changes to be significantly enhanced on a topography Ra of ~40 nm with clinical implications therein for implant surface treatment and generation.
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The demographic challenges of an increasingly aging population emphasize the need for innovative approaches to skeletal reconstruction to augment and repair skeletal tissue lost as a consequence of implant loosening, trauma, degeneration or in situations involving revision surgery requiring bone stock. These clinical imperatives to augment skeletal tissue loss have brought mesenchymal stem cells to the fore in combination with the emerging discipline of tissue engineering. To date, impaction bone grafting for revision hip surgery is a recognized technique to reconstitute bone utilizing morselized allograft to provide a good mechanical scaffold, although with little osteoinductive biological potential. This review details laboratory and clinical examples of a paradigm shift in the application of mesenchymal stem cells with allograft to produce a living composite using the principles of tissue engineering. This step change creates a composite that offers a biological and mechanical advantage over the current gold standard of allograft alone. This translation of tissue engineering concepts into clinical practice offers enormous input into the field of bone regeneration and has implications for translation and future change in skeletal orthopedic practice in an increasingly aging population.
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Sustitutos de Huesos , Trasplante Óseo , Células Madre Mesenquimatosas/citología , Ingeniería de Tejidos/métodos , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera , Regeneración Ósea , Resorción Ósea/cirugía , Sustitutos de Huesos/provisión & distribución , Sustitutos de Huesos/uso terapéutico , Humanos , Trasplante de Células Madre MesenquimatosasRESUMEN
In contrast to traditional approaches to fracture risk assessment using clinical risk factors and bone mineral density (BMD), a new technique, reference point microindentation (RPI), permits direct assessment of bone quality; in vivo tibial RPI measurements appear to discriminate patients with a fragility fracture from controls. However, it is unclear how this relates to the site of the most clinically devastating fracture, the femoral neck, and whether RPI provides information complementary to that from existing assessments. Femoral neck samples were collected at surgery after low-trauma hip fracture (n = 46; 17 male; aged 83 [interquartile range 77-87] years) and compared, using RPI (Biodent Hfc), with 16 cadaveric control samples, free from bone disease (7 male; aged 65 [IQR 61-74] years). A subset of fracture patients returned for dual-energy X-ray absorptiometry (DXA) assessment (Hologic Discovery) and, for the controls, a micro-computed tomography setup (HMX, Nikon) was used to replicate DXA scans. The indentation depth was greater in femoral neck samples from osteoporotic fracture patients than controls (p < 0.001), which persisted with adjustment for age, sex, body mass index (BMI), and height (p < 0.001) but was site-dependent, being less pronounced in the inferomedial region. RPI demonstrated good discrimination between fracture and controls using receiver-operating characteristic (ROC) analyses (area under the curve [AUC] = 0.79 to 0.89), and a model combining RPI to clinical risk factors or BMD performed better than the individual components (AUC = 0.88 to 0.99). In conclusion, RPI at the femoral neck discriminated fracture cases from controls independent of BMD and traditional risk factors but dependent on location. The clinical RPI device may, therefore, supplement risk assessment and requires testing in prospective cohorts and comparison between the clinically accessible tibia and the femoral neck. © 2015 American Society for Bone and Mineral Research.
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Absorciometría de Fotón , Índice de Masa Corporal , Fracturas del Cuello Femoral , Cuello Femoral , Anciano , Anciano de 80 o más Años , Femenino , Fracturas del Cuello Femoral/diagnóstico por imagen , Fracturas del Cuello Femoral/epidemiología , Fracturas del Cuello Femoral/metabolismo , Cuello Femoral/diagnóstico por imagen , Cuello Femoral/metabolismo , Humanos , Masculino , Medición de RiesgoRESUMEN
The development of an osteogenic bone graft substitute has important practical and cost implications in many branches of medicine where bone regeneration is required. Previous in vitro and small animal (murine) in vivo studies highlighted a porous hydroxyapatite/poly (DL-lactic acid) composite scaffold in combination with skeletal stem cells (SSCs) as a potential bone graft substitute candidate. The aim of the current study was to scale up the bone cell-scaffold construct to large animals and examine the potential for repair of a critical-sized defect via an ovine model. SSC seeded scaffolds (and unseeded scaffold controls) were implanted bilaterally into ovine femoral condyle critical defects for 3 months. A parallel in vitro analysis of ovine SSC seeded scaffolds was also performed. Post mortem mechanical indentation testing showed the bone strengths of the defect sites were 20% (controls) and 11% (SSC seeded scaffolds) those of normal cancellous bone (p < 0.01). MicroCT analysis demonstrated new bone formation within all defects with a mean increase of 13.4% in the control scaffolds over the SSC seeded scaffolds (p = 0.14). Histological examination confirmed these findings, with enhanced quality new bone within the control defects. This study highlights important issues and steps to overcome in scale-up and translation of tissue engineered products. The scaffold demonstrated encouraging results as an osteoconductive matrix; however, further work is required with cellular protocols before any human trials.
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Regeneración Ósea/efectos de los fármacos , Durapatita/farmacología , Fémur/patología , Polímeros/farmacología , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Fosfatasa Alcalina/metabolismo , Animales , Fémur/diagnóstico por imagen , Fémur/efectos de los fármacos , Fémur/cirugía , Humanos , Ganglios Linfáticos/efectos de los fármacos , Ensayo de Materiales , Porosidad , Oveja Doméstica , Células Madre/citología , Células Madre/efectos de los fármacos , Estrés Mecánico , Microtomografía por Rayos XRESUMEN
BACKGROUND: When fresh morselized graft is compacted, as in impaction bone-grafting for revision hip surgery, fat and marrow fluid is either exuded or trapped in the voids between particles. We hypothesized that the presence of incompressible fluid damps and resists compressive forces during impaction and prevents the graft particles from moving into a closer formation, thus reducing the graft strength. In addition, viscous fluid such as fat may act as an interparticle lubricant, thus reducing the interlocking of the particles. METHODS: We performed mechanical shear testing in the laboratory with use of fresh-frozen human femoral-head allografts that had been passed through different orthopaedic bone mills to produce graft of differing particle-size distributions (grading). RESULTS: After compaction of fresh graft, fat and marrow fluid continued to escape on application of normal loads. Washed graft, however, had little lubricating fluid and better contact between the particles, increasing the shear resistance. On mechanical testing, washed graft was significantly (p < 0.001) more resistant to shearing forces than fresh graft was. This feature was consistent for different bone mills that produced graft of different particle-size distributions and shear strengths. CONCLUSIONS: Removal of fat and marrow fluid from milled human allograft by washing the graft allows the production of stronger compacted graft that is more resistant to shear, which is the usual mode of failure. Further research into the optimum grading of particle sizes from bone mills is required.
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Trasplante Óseo/métodos , Huesos/fisiología , Resistencia al Corte , Manejo de Especímenes/métodos , Humanos , Tamaño de la Partícula , TrasplantesRESUMEN
BACKGROUND: Strategies to improve mechanical strength, neovascularization, and the regenerative capacity of allograft include both the addition of skeletal stem cells and the investigation of novel biomaterials to reduce and ultimately obviate the need for allograft altogether. Use of bone cement is a common method of stabilizing implants in conjunction with impacted allograft. Curing cement, however, can reach temperatures in excess of 70°C, which is potentially harmful to skeletal stem cells. The aim of this study was to investigate the effects of setting bone cement on the survival of human adult skeletal stem cells within tissue-engineered allograft and a novel allograft substitute. METHODS: Milled allograft and a polymer graft substitute were seeded with skeletal stem cells, impacted into a graduated chamber, and exposed to curing bone cement. Sections were removed at 5-mm increments from the allograft-cement interface. A quantitative WST-1 assay was performed on each section as a measure of remaining cell viability. A second stage of the experiment involved assessment of methods to potentially enhance cell survival, including pretreating the allograft or polymer by either cooling to 5°C or coating with 1% Laponite, or both. RESULTS: There was a significant drop in cellular activity in the sections taken from within 0.5 cm of the cement interface in both the allograft and the polymer (p < 0.05), although there was still measurable cellular activity. Pretreatment methods did not significantly improve cell survival in any group. CONCLUSIONS: While the addition of bone cement reduced cellular viability of tissue-engineered constructs, this reduction occurred only in close proximity to the cement and measurable numbers of skeletal stem cells were observed, confirming the potential for cell population recovery.
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Cementos para Huesos , Sustitutos de Huesos , Trasplante Óseo , Células Madre/fisiología , Ingeniería de Tejidos , Anciano , Anciano de 80 o más Años , Técnicas de Cultivo de Célula , Supervivencia Celular , Durapatita , Humanos , Masculino , Poliésteres , Andamios del TejidoRESUMEN
Impaction bone grafting (IBG) with human allograft remains the preferred approach for replacement of lost bone stock during revision hip surgery. Associated problems include cost, disease transmission, and stem subsidence. Synthetic grafts are therefore appealing, and ideally display similar mechanical characteristics as allograft, but with enhanced ability to form de novo bone. High and low molecular weight forms of three different polymers [poly(DL-lactide) (P(DL) LA), poly(DL-lactide-co-glycolide) (P(DL) LGA), and poly(ε-caprolactone) (PCL)] were milled, impacted into discs, and then examined in a shear testing rig, in comparison to allograft. In addition, skeletal stem cells (SSCs) were combined with each of the milled polymers, followed by impaction and examination for cell viability and number, via fluorostaining and biochemical assays. The shear strengths of high/low mwt P(DL) LA, and high/low mwt P(DL) LGA were significantly higher than allograft (p < 0.01). High/low mwt PCL had significantly lower shear strengths (p < 0.01). WST-1 assay and fluorstaining indicated significantly increased cell viability on high mwt P(DL) LA and high mwt P(DL) LGA over allograft (p < 0.05). Mechanical and biochemical analysis indicated improved properties of high mwt P(DL) LA and high mwt P(DL) LGA over allograft. This study indicates the potential of these polymers for use as substitute human allograft, creating a living composition with SSC for application in IBG.
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Materiales Biocompatibles/farmacología , Trasplante Óseo , Ensayo de Materiales/métodos , Fenómenos Mecánicos/efectos de los fármacos , Polímeros/química , Anciano , Recuento de Células , Proliferación Celular/efectos de los fármacos , Humanos , Inmunohistoquímica , Masculino , Microscopía Electrónica de Rastreo , Resistencia al Corte/efectos de los fármacos , Células Madre/citología , Células Madre/efectos de los fármacos , Trasplante Homólogo , Microtomografía por Rayos XRESUMEN
Loss of skeletal tissue as a consequence of trauma, injury, or disease is a significant cause of morbidity with often wide-ranging socioeconomic impacts. Current approaches to replace or restore significant quantities of lost bone come with substantial limitations and inherent disadvantages that may in themselves cause further disability. In addition, the spontaneous repair capacity of articular cartilage is limited; thus, investigation into new cartilage replacement and regeneration techniques are warranted. Along with the challenges of an increasingly aging demographic, changing clinical scenarios and rising functional expectations provide the imperative for new, more reliable skeletal regeneration strategies. The science of tissue engineering has expanded dramatically in recent years, notably in orthopedic applications, and it is clear that new approaches for de novo skeletal tissue formation offer exciting opportunities to improve the quality of life for many, particularly in the face of increasing patient expectations. However, significant scientific, financial, industrial, and regulatory challenges should be overcome before the successful development of an emergent tissue engineering strategy can be realized. We outline current practice for replacement of lost skeletal tissue and the innovative approaches in tissue regeneration that have so far been translated to clinical use, along with a discussion of the significant hurdles that are presented in the process of translating research strategies to the clinic.
Asunto(s)
Envejecimiento/fisiología , Regeneración Ósea/fisiología , Medicina Regenerativa/métodos , Medicina Regenerativa/tendencias , Distribución por Edad , Humanos , Investigación Biomédica TraslacionalRESUMEN
AIM: Tissue engineering has enormous potential for the regeneration of bone defects. Approximately 4 years ago we reported on a 62 year old patient who underwent treatment of a benign cyst in the proximal femur by impaction bone grafting supplemented with autologous bone marrow. The cyst and symptoms subsequently recurred and this patient has now required a total hip replacement. This has provided a rare opportunity for ex vivo analysis of clinically applied tissue engineered bone. MATERIALS & METHODS: The femoral head was retrieved at surgery and the structural and functional characteristics of the tissue engineered bone were analyzed by micro-computed tomography, histology and mechanical testing. RESULTS: The impacted bone demonstrated a trabecular structure that contained islands of nonincorporated graft. The graft was denser than the patient's trabecular bone with comparable strength. The cyst material had penetrated along the channel of bone and an increased number of osteoclasts were observed. DISCUSSION: This study has provided detailed ex vivo analysis of retrieved human tissue engineered bone and possible reasons for the observed construct failure are discussed in this article. The impacted bone displayed some evidence of remodeled trabecular structure, although the bone marrow aspirate that was initially combined with the allograft contained a relatively low concentration of osteoprogenitor cells. Cellular augmentation was insufficient to overcome the osteoclastic process associated with renewed cyst formation. Concentration or culture expansion of osteoprogenitor cells from aspirated bone marrow is recommended for biological augmentation of bone graft.