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BACKGROUND: Bioresorbable patient-specific additive-manufactured bone grafts, meshes, and plates are emerging as a promising alternative that can overcome the challenges associated with conventional off-the-shelf implants. The fabrication of patient-specific implants (PSIs) directly at the point-of-care (POC), such as hospitals, clinics, and surgical centers, allows for more flexible, faster, and more efficient processes, reducing the need for outsourcing to external manufacturers. We want to emphasize the potential advantages of producing bioresorbable polymer implants for cranio-maxillofacial surgery at the POC by highlighting its surgical applications, benefits, and limitations. METHODS: This study describes the workflow of designing and fabricating degradable polymeric PSIs using three-dimensional (3D) printing technology. The cortical bone was segmented from the patient's computed tomography data using Materialise Mimics software, and the PSIs were designed created using Geomagic Freeform and nTopology software. The implants were finally printed via Arburg Plastic Freeforming (APF) of medical-grade poly (L-lactide-co-D, L-lactide) with 30% ß-tricalcium phosphate and evaluated for fit. RESULTS: 3D printed implants using APF technology showed surfaces with highly uniform and well-connected droplets with minimal gap formation between the printed paths. For the plates and meshes, a wall thickness down to 0.8 mm could be achieved. In this study, we successfully printed plates for osteosynthesis, implants for orbital floor fractures, meshes for alveolar bone regeneration, and bone scaffolds with interconnected channels. CONCLUSIONS: This study shows the feasibility of using 3D printing to create degradable polymeric PSIs seamlessly integrated into virtual surgical planning workflows. Implementing POC 3D printing of biodegradable PSI can potentially improve therapeutic outcomes, but regulatory compliance must be addressed.
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BACKGROUND: Nonunion and plate exposure represent a major complication after mandibular reconstruction with free fibula flaps. These drawbacks may be resolved by geometric osteotomies increasing intersegmental bone contact area and stability. PURPOSE: The aim of this study was to compare intersegmental bone contact and stability of geometric osteotomies to straight osteotomies in mandibular reconstructions with free fibula grafts performed by robot-guided erbium-doped yttrium aluminum garnet laser osteotomy. STUDY DESIGN, SETTING, SAMPLE: This cadaveric in-vitro study was performed on fresh frozen human skull and fibula specimens. Computed tomography (CT) scans of all specimens were performed for virtual planning of mandibular resections and three-segment fibula reconstructions. The virtual planning was implemented in a Cold Ablation Robot-guided Laser Osteotome. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: For predictor variables, straight and geometric puzzle-shaped osteotomies were designed at resection of the mandible and corresponding fibula reconstruction. MAIN OUTCOME VARIABLES: The primary outcome variable was the stability of the reconstructed mandible investigated by shearing tests. Moreover, secondary outcome variables were the duration of the laser osteotomies, the contact surface area, and the accuracy of the reconstruction, both evaluated on postsurgical CT scans. COVARIATES: Covariables were not applicable. ANALYSES: Data were reported as mean values (± standard deviation) and were statistically analyzed using an independent-sample t-test at a significance level of α = 0.05. Root mean square deviation was tested for accuracy. RESULTS: Eight skulls and 16 fibula specimens were used for the study. One hundred twelve successful laser osteotomies (96 straight and 16 geometrical) could be performed. Geometric osteotomies increased stability (110.2 ± 36.2 N vs 37.9 ± 20.1 N, P < .001) compared to straight osteotomies. Geometric osteotomy of the fibula took longer than straight osteotomies (10.9 ± 5.1 min vs 5.9 ± 2.2 min, P = .028) but could provide larger contact surface (431.2 ± 148.5 mm2 vs 226.1 ± 50.8 mm2, P = .04). Heat map analysis revealed a mean deviation between preoperational planning and postreconstructive CT scan of -0.8 ± 2.4 mm and a root mean square deviation of 2.51 mm. CONCLUSION AND RELEVANCE: Mandibular resection and reconstruction by fibula grafts can be accurately performed by a Cold Ablation Robot-guided Laser Osteotome without need for cutting guides. Osteotomy planning with geometric cuts offers higher stability and an increased bone contact area, which may enhance healing of the reconstructed mandible.
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Retalhos de Tecido Biológico , Reconstrução Mandibular , Humanos , Reconstrução Mandibular/métodos , Fíbula/transplante , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Osteotomia/métodos , Retalhos de Tecido Biológico/transplante , LasersRESUMO
Autologous bone remains the gold standard bone substitute in clinical practice. Therefore, the microarchitecture of newly developed synthetic bone substitutes, which reflects the spatial distribution of materials in the scaffold, aims to recapitulate the natural bone microarchitecture. However, the natural bone microarchitecture is optimized to obtain a mechanically stable, lightweight structure adapted to the biomechanical loading situation. In the context of synthetic bone substitutes, the application of a Triply Periodic Minimum Surface (TPMS) algorithm can yield stable lightweight microarchitectures that, despite their demanding architectural complexity, can be produced by additive manufacturing. In this study, we applied the TPMS derivative Adaptive Density Minimal Surfaces (ADMS) algorithm to produce scaffolds from hydroxyapatite (HA) using a lithography-based layer-by-layer methodology and compared them with an established highly osteoconductive lattice microarchitecture. We characterized them for compression strength, osteoconductivity, and bone regeneration. The in vivo results, based on a rabbit calvaria defect model, showed that bony ingrowth into ADMS constructs as a measure of osteoconduction depended on minimal constriction as it limited the maximum apparent pore diameter in these scaffolds to 1.53 mm. Osteoconduction decreased significantly at a diameter of 1.76 mm. The most suitable ADMS microarchitecture was as osteoconductive as a highly osteoconductive orthogonal lattice microarchitecture in noncritical- and critical-size calvarial defects. However, the compression strength and microarchitectural integrity in vivo were significantly higher for scaffolds with their microarchitecture based on the ADMS algorithm when compared with high-connectivity lattice microarchitectures. Therefore, bone substitutes with high osteoconductivity can be designed with the advantages of the ADMS-based microarchitectures. As TPMS and ADMS microarchitectures are true lightweight structures optimized for high mechanical stability with a minimal amount of material, such microarchitectures appear most suitable for bone substitutes used in clinical settings to treat bone defects in weight-bearing and non-weight-bearing sites.
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Despite the recent advances in 3D-printing, it is often difficult to fabricate implants that optimally fit a defect size or shape. There are some approaches to resolve this issue, such as patient-specific implant/scaffold designs based on CT images of the patients, however, this process is labor-intensive and costly. Especially in developing countries, affordable treatment options are required, while still not excluding these patient groups from potential material and manufacturing advances. Here, a selective laser melting (SLM) 3D-printing strategy was used to fabricate a hierarchical, LEGO®-inspired Assemblable Titanium Scaffold (ATS) system, which can be manually assembled in any shape or size with ease. A surgeon can quickly create a scaffold that would fit to the defect right before the implantation during the surgery. Additionally, the direct inclusion of micro- and macroporous structures via 3D-printing, as well as a double acid-etched surface treatment (ST) in the ATS, ensure biocompatibility, sufficient nutrient flow, cell migration and enhanced osteogenesis. Three different structures were designed (non-porous:NP, semi-porous:SP, ultra-porous:UP), 3D-printed with the SLM technique and then surface treated for the ST groups. After analyzing characteristics of the ATS such as printing quality, surface roughness and interconnected porosity, mechanical testing and finite element analysis (FEA) demonstrated that individual and stacked ATS have sufficient mechanical properties to withstand loading in a physiological system. All ATS showed high cell viability, and the SP and UP groups demonstrated enhanced cell proliferation rates compared to the NP group. Furthermore, we also verified that cells were well-attached and spread on the porous structures and successful cell migration between the ATS units was seen in the case of assemblies. The UP and SP groups exhibited higher calcium deposition and RT-qPCR proved higher osteogenic gene expression compared to NP group. Finally, we demonstrate a number of possible medical applications that reveal the potential of the ATS through assembly.
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Medicina Regenerativa , Titânio , Humanos , Osteogênese , Próteses e Implantes , Impressão TridimensionalRESUMO
Only a few mandibular bone finite element (FE) models have been validated in literature, making it difficult to assess the credibility of the models. In a comparative study between FE models and biomechanical experiments using a synthetic polyamide 12 (PA12) mandible model, we investigate how material properties and boundary conditions affect the FE model's accuracy using the design of experiments approach. Multiple FE parameters, such as contact definitions and the materials' elastic and plastic deformation characteristics, were systematically analyzed for an intact mandibular model and transferred to the fracture fixation model. In a second step, the contact definitions for the titanium screw and implant (S-I), implant and PA12 mandible (I-M), and interfragmentary (IF) PA12 segments were optimized. Comparing simulated deformations (from 0 to -5 mm) and reaction forces (from 10 to 1'415 N) with experimental results showed a strong sensitivity to FE mechanical properties and contact definitions. The results suggest that using the bonded definition for the screw-implant contact of the fracture plate is ineffective. The contact friction parameter set with the highest agreement was identified: titanium screw and implant µ = 0.2, implant and PA12 mandible µ = 0.2, interfragmentary PA12 mandible µ = 0.1. The simulated reaction force (RMSE = 26.60 N) and surface displacement data (RMSE = 0.19 mm) of the FE analysis showed a strong agreement with the experimental biomechanical data. The results were generated through parameter optimization which means that our findings need to be validated in the event of a new dataset with deviating anatomy. Conclusively, the predictive capability of the FE model can be improved by FE model calibration through experimental testing. Validated preoperative quasi-static FE analysis could allow engineers and surgeons to accurately estimate how the implant's choice and placement suit the patient's biomechanical needs.
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Fraturas Mandibulares , Humanos , Fraturas Mandibulares/cirurgia , Análise de Elementos Finitos , Titânio , Fixação Interna de Fraturas/métodos , Fenômenos Biomecânicos , Mandíbula , Placas Ósseas , Estresse MecânicoRESUMO
Bone graft materials are applied in patients to augment bone defects and enable the insertion of an implant in its ideal position. However, the currently available augmentation materials do not meet the requirements of being completely resorbed and replaced by new bone within 3 to 6 months. A novel electrospun cotton-wool like material (Bonewool®, Zurich Biomaterials LLC, Zurich, Switzerland) consisting of biodegradable poly(lactic-co-glycolic) acid (PLGA) fibers with incorporated amorphous ß-tricalcium phosphate (ß-TCP) nanoparticles has been compared to a frequently used bovine derived hydroxyapatite (Bio-Oss®, Geistlich Pharma, Wolhusen, Switzerland) in vitro. The material composition was determined and the degradation behavior (calcium release and pH in different solutions) as well as bioactivity has been measured. Degradation behavior of PLGA/ß-TCP was generally more progressive than for Bio-Oss®, indicating that this material is potentially completely resorbable. Graphical abstract.
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Substitutos Ósseos , Fosfatos de Cálcio , Animais , Materiais Biocompatíveis/química , Fosfatos de Cálcio/química , Bovinos , HumanosRESUMO
BACKGROUND: Cheese-wiring, the suture that cuts through the meniscus, is a well-known issue in meniscal repair. So far, contributing factors are neither fully understood nor sufficiently studied. HYPOTHESIS/PURPOSE: To investigate whether the construct stiffness of repair sutures and devices correlates with suture cut-through (cheese-wiring) during load-to-failure testing. STUDY DESIGN: Controlled laboratory study. METHODS: In 131 porcine menisci, longitudinal bucket-handle tears were repaired using either inside-out sutures (n = 66; No. 0 Ultrabraid, 2-0 Orthocord, 2-0 FiberWire, and 2-0 Ethibond) or all-inside devices (n = 65; FastFix360, Omnispan, and Meniscal Cinch). After cyclic loading, load-to-failure testing was performed. The mode of failure and construct stiffness were recorded. A receiver operating characteristic curve analysis was performed to define the optimal stiffness threshold for predicting meniscal repair failure by cheese-wiring. The 2-tailed t test and analysis of variance were used to test significance. RESULTS: Loss of suture fixation was the most common mode of failure in all specimens (58%), except for the Omnispan, which failed most commonly because of anchor pull-through. The Omnispan demonstrated the highest construct stiffness (30.8 ± 3.5 N/mm), whereas the Meniscal Cinch (18.0 ± 8.8 N/mm) and Ethibond (19.4 ± 7.8 N/mm) demonstrated the lowest construct stiffness. The Omnispan showed significantly higher stiffness compared with the Meniscal Cinch (P < .001) and Ethibond (P = .02), whereas the stiffness of the Meniscal Cinch was significantly lower compared with that of the FiberWire (P = .01), Ultrabraid (P = .04), and FastFix360 (P = .03). While meniscal repair with a high construct stiffness more often failed by cheese-wiring, meniscal repair with a lower stiffness failed by loss of suture fixation, knot slippage, or anchor pull-through. Meniscal repair with a stiffness >26.5 N/mm had a 3.6 times higher risk of failure due to cheese-wiring during load-to-failure testing (95% CI, 1.4-8.2; P < .0001). CONCLUSION: Meniscal repair using inside-out sutures and all-inside devices with a higher construct stiffness (>26.5 N/mm) was more likely to fail through suture cut-through (cheese-wiring) than that with a lower stiffness (≤26.5 N/mm). CLINICAL RELEVANCE: This is the first study investigating the impact of construct stiffness on meniscal repair failure by suture cut-through (cheese-wiring).
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BACKGROUND: Previous biomechanical studies used single-pull destructive tests in line with the anchor and are limited by a great variability of bone density of cadaver samples. To overcome these limitations, a more physiological test setting was provided using titanium, bioresorbable, and all-suture anchors. METHODS: In this controlled laboratory study, 3 anchor constructs were divided into 2 groups: physiological and osteoporotic. Sixty standardized artificial bone specimens (=10 for each anchor in each group) were used for biomechanical testing. The anchors were inserted at a 45° angle as during surgery. Cyclic loading for 1000 cycles followed by ultimate load-to-failure (ULTF) testing was performed. Elongation, ultimate load at failure, and the mode of failure were noted. RESULTS: In the physiological group, the ULTF for the all-suture anchor (mean [standard deviation], 632.9 [96.8 N]) was found to be significantly higher than for the other anchors (titanium, 497.1 [50.5] N, and bioresorbable, 322.4 [3.1 N], P < .0001). The titanium anchor showed a significantly higher ULTF than the bioresorbable anchor (P < .0001). In the osteoporotic group, the all-suture anchor again showed a higher ULTF compared to the bioresorbable anchor (500.9 [50.6] N vs. 315.1 [11.3] N, P < .0001). In the osteoporotic group, cyclic loading revealed a higher elongation after 1000 loading cycles for the bioresorbable (0.40 [0.12] mm) compared to the titanium (0.22 [0.11] mm; P = .01) as well as the all-suture anchor (0.19 [0.15] mm, P = .003). CONCLUSION: Regarding ULTF, the all-suture anchor outperformed the other anchors in physiological bone, but in osteoporotic bone, significance was reached only compared to the bioresorbable anchor. Although cyclic loading revealed significant differences, these might not be clinically relevant.
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Implantes Absorvíveis , Lesões do Manguito Rotador/cirurgia , Âncoras de Sutura , Titânio , Artroplastia , Fenômenos Biomecânicos , Densidade Óssea , Osso e Ossos/fisiologia , Humanos , Teste de Materiais , Osteoporose/fisiopatologia , Falha de PróteseRESUMO
PURPOSE: Suprapectoral tenodesis is a frequently used technique for treating pathologies of the long head of the biceps brachii (LHBB) tendon. However, so far, no Gold Standard treatment exist. Hence, the arthroscopic LassoLoop360 (LL360) technique is introduced aiming to provide secure fixation and improved biomechanical properties. It was hypothesized, that the LL360 technique would show superior biomechanical response to cyclic loading and ultimate load-to-failure testing compared to the commonly used simple Lasso Loop (SLL). METHODS: Twenty-two porcine superficial flexor digitorum tendons were prepared using a No. 2 suture according to either the SLL or the LL360 technique. Displacement after cyclic loading (1.000 cycles) between 5 and 30 N, ultimate load-to-failure (ULTF), mode of failure as well as the construct stiffness were tested. RESULTS: Significantly less displacement was found in the LL360 group (SLL 2.25 ± 0.51 mm; LL360 1.67 ± 0.37 mm; p = 0.01). Ultimate Load to Failure was significantly higher in the LL360 (168.6 ± 29.6 N) as compared to the SLL (124.1 ± 25.8 N, p = 0.02). The LL360 also revealed a significant higher stiffness compared to the SLL (SLL 13.1 ± 0.9 N/mm vs. LL360 19.1 ± 1.0 N/mm, p < 0.001). The most common mode of failure was the suture cutting through the tendon, with a significantly less suture cutting through for the LL360 compared with the SLL (p < 0.05). CONCLUSION: The LassoLoop360-technique offers superior biomechanical characteristics regarding the tendon-suture-interface compared to the SLL. In the initial healing phase, the suture-tendon-interface is the most vulnerable part of the tendon-suture-anchor construct, the aim of this new technique is to reduce this weakest part of the chain (Ponce et al., Am J Sports Med 39:188-194, 2011). This technique may therefore be beneficial for arthroscopic suprapectoral biceps tenodesis at the entrance of the bicipital groove.
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Artroscopia/métodos , Técnicas de Sutura , Traumatismos dos Tendões/cirurgia , Animais , Modelos Animais , Estresse Mecânico , Suínos , Resistência à TraçãoRESUMO
Additive manufacturing of bone tissue engineering scaffolds will become a key element for personalized bone tissue engineering in the near future. Several additive manufacturing processes are based on extrusion where the deposition of the filament will result in a three-dimensional lattice structure. Recently, we studied diverse lattice structures for bone tissue engineering realized by laser sintering of titanium. In this work, we used lithography-based ceramic manufacturing of lattice structures to produce scaffolds from tricalcium phosphates (TCP) and compared them in vivo to congruent titanium scaffolds manufactured with the identical computer-aided design data to look for material-based differences in bony healing. The results show that, during a 4-week period in a noncritical-size defect in a rabbit calvarium, both scaffolds with the identical microarchitecture performed equally well in terms of bony regeneration and bony bridging of the defect. A significant increase in both parameters could only be achieved when the TCP-based scaffolds were doped with bone morphogenetic protein-2. In a critical-size defect in the calvarial bone of rabbits, however, the titanium scaffold performed significantly better than the TCP-based scaffold, most likely due to its higher mechanical stability. We conclude that titanium and TCP-based scaffolds of the same microarchitecture perform equally well in terms of bone regeneration, provided the microarchitecture meets the mechanical demand at the site of implantation.
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Osso e Ossos/fisiologia , Fosfatos de Cálcio/farmacologia , Engenharia Tecidual/métodos , Titânio/farmacologia , Animais , Osso e Ossos/efeitos dos fármacos , Coelhos , Crânio/efeitos dos fármacos , Crânio/patologia , Alicerces Teciduais/químicaRESUMO
BACKGROUND: Silver ions (Ag+) have strong antibacterial effects, and silver-coated materials are in widespread clinical use. However, the application of silver-coated medical devices is not without concerns: its use with direct bone contact is not established, and systemic toxic side effects of released Ag+ have been described. Therefore, alternative bactericidal coatings with a more localized way of acting - e.g., calcium dihydroxide, Ca(OH)2 (CH) - would be advantageous. METHODS: A new rat model of the animal's tibial metaphysis was developed. In the left proximal tibiae of 36 male Wistar rats, titanium screws were implanted. The screws were coated with hydroxyapatite (HA; 12 animals: group I), low-dosed HA silver (HA-Ag; 12 animals: group II) and CH (12 animals: group III). After 6 weeks, all rats were sacrificed. The implants were evaluated for morphological changes on their surfaces, by light microscopy, scanning electron microscopy and energy-dispersive X-ray spectroscopy; for osteointegration, by measurement of resistance to removal; and for bacterial colonization, by quantitative culture analysis. Additionally, the tibial bone was investigated histologically for signs of osteomyelitis and sonicated to detect bacterial loads. RESULTS: (i) No microbiological or histological signs of infection could be determined on any of the screws or the surrounding bone. (ii) The bone-implant interface analysis revealed extensive bone formation and direct bone-implant contact on all HA, HA-Ag and HA-CH coated screws. (iii) HA and HA-Ag were partially, and CH was fully, degraded on the screw coating, allowing host bone to osteointegrate.
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Parafusos Ósseos , Hidróxido de Cálcio/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Prata/farmacologia , Tíbia/metabolismo , Animais , Masculino , Ratos , Ratos Wistar , Tíbia/patologiaRESUMO
BACKGROUND: Animal models serve as an important tool to understand peri-implant infection. Most of the models use high bacterial loads (>10(4) colony forming units, CFU) to provide high infection rates. Therefore these animals evolve rather similarly, making comparison between groups and statistical analysis possible. On the other hand, to mimic clinical constellation of surgery-related infections the use of low amounts of bacteria would be more advantageous. METHODS: We developed a metaphyseal rat model of peri-implant bone infection with low amount of bacterial loads (10(2) and 10(3) CFU of Staphylococcus aureus) and investigated osseointegration of the implants coated with hydroxyapatite (HA) and low-dosed HA-silver (HA-Ag). Non-infected implants served as controls. After 6 weeks rats were sacrificed and implants evaluated for osseointegration and infection. RESULTS: Infection of implanted devices was reliably induced, independently whether 10(2) or 10(3) CFU of S. aureus were inoculated and HA or HA-Ag coated implants were used. No systemic infection was present in any of the animals at the time of sacrifice, and no animal developed acute infection requiring premature sacrifice. All CFU counts of the implant and the bone at sacrifice were significantly higher than the inoculated load (p < .05). All sterilely inserted implants showed excellent osseointegration and no infection. CONCLUSIONS: Our present study of a rat tibia model reliably induced osteomyelitis in the metaphysis with low-doses of bacteria. The addition of low-dosed Ag to the implant coating was not able to reduce the infection rates. The results demonstrate that it is possible to develop a model of implant-related osteomyelitis in rats with low amounts of bacteria to better mimic clinical constellations. No other promoters of infection besides insertion of the screw implant were used in this model.
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Parafusos Ósseos/microbiologia , Modelos Animais de Doenças , Osteomielite/diagnóstico por imagem , Infecções Estafilocócicas/diagnóstico por imagem , Staphylococcus aureus , Animais , Parafusos Ósseos/efeitos adversos , Masculino , Osteomielite/etiologia , Osteomielite/patologia , Ratos , Ratos Wistar , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/patologiaRESUMO
Resorbable bone substitute materials are widely used for bone augmentation after tumor resection, parallel to implant placement, or in critical size bone defects. In this study, the structural dissolution of a biphasic calcium phosphate bone substitute material with a hydroxyapatite (HA)/tricalcium phosphate (ß-TCP) ratio of 60/40 was investigated by repeatedly placing porous blocks in EDTA solution at 37 °C. At several time points, the blocks were investigated by SEM, µCT, and gravimetry. It was found that always complete 2-3 µm sized grains were removed from the structure and that the ß-TCP is dissolved more rapidly. This selective dissolution of the ß-TCP grains was confirmed by XRD measurements. The blocks were eroded from the outside toward the center. The structure remained mechanically stable because the central part showed a delayed degradation and because the slower dissolving HA grains preserved the integrity of the structure.
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Fosfatos de Cálcio/química , Cerâmica/química , Durapatita/química , Microscopia Eletrônica de Varredura , Difração de Raios X , Microtomografia por Raio-XRESUMO
Secondary bone fracture healing is a physiological process that leads to functional tissue regeneration via endochondral bone formation. In vivo studies have demonstrated that early mobilization and the application of mechanical loads enhances the process of fracture healing. However, the influence of specific mechanical stimuli and particular effects during specific phases of fracture healing remain to be elucidated. In this work, we have developed and provided proof-of-concept of an in vitro human organotypic model of physiological loading of a cartilage callus, based on a novel perfused compression bioreactor (PCB) system. We then used the fracture callus model to investigate the regulatory role of dynamic mechanical loading. Our findings provide a proof-of-principle that dynamic mechanical loading applied by the PCB can enhance the maturation process of mesenchymal stromal cells toward late hypertrophic chondrocytes and the mineralization of the deposited extracellular matrix. The PCB provides a promising tool to study fracture healing and for the in vitro assessment of alternative fracture treatments based on engineered tissue grafts or pharmaceutical compounds, allowing for the reduction of animal experiments.
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Bone morphogenetic proteins (BMPs) are growth and differentiation factors involved during development in morphogenesis, organogenesis and later mainly in regeneration processes, in particular in bone where they are responsible for osteoinduction. For more than a decade, recombinant human (rh)BMP-2 has been used in the clinic for lumbar spinal fusion at non-physiological high dosages that appear to be causative for side effects, like male sterility. A possible strategy to reduce the effective amount of rhBMP-2 in the clinic is the co-delivery with an enhancer of BMPs' activity. In an earlier study, we showed that N-methylpyrrolidone (NMP) enhances BMP activity in vitro and in vivo. Here we report on the development of a slow and sustained double delivery of rhBMP-2 and NMP via an in situ forming implant based on poly(lactide-co-glycolide). The results showed that the release of NMP can be adjusted by varying the lactide/glycolide ratio and the polymer's molecular weight. The same applied to rhBMP-2, with release rates that could be sustained from two to three weeks. In the in vivo model of a critical size defect in the calvarial bone of rabbits, the implant containing 50mol% lactide performed better than the one having 75mol% lactide in terms of defect bridging and extent of bony regenerated area. In situ forming implants for the double delivery of the BMP enhancer NMP and rhBMP-2 appear to be promising delivery systems in bone regeneration.
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Proteína Morfogenética Óssea 2/administração & dosagem , Implantes de Medicamento/química , Osteogênese/efeitos dos fármacos , Poliglactina 910/química , Pirrolidinonas/administração & dosagem , Crânio/efeitos dos fármacos , Crânio/lesões , Fator de Crescimento Transformador beta/administração & dosagem , Animais , Proteína Morfogenética Óssea 2/farmacologia , Pirrolidinonas/farmacologia , Coelhos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Crânio/fisiologia , Fator de Crescimento Transformador beta/farmacologiaRESUMO
Biomaterials with antimicrobial properties are now commonly used in different clinical specialties including orthopedics, endodontic, and traumatology. As a result, assessing the antimicrobial effect of coatings applied on implants is of critical importance. In this study, we demonstrate that isothermal microcalorimetry (IMC) can be used for monitoring bacterial growth and biofilm formation at the surface of such coatings and for determining their antimicrobial effects. The antibacterial effects of silver doped hydroxyapatite (HA) and calcium hydroxide coatings on Staphylococcus epidermidis were determined with a minimal workload. Using the Gompertz growth model we determined biofilm growth rates close to those values reported in the literature. Furthermore, we were able to estimate the reduction in the bacterial inocula originally applied at the surface of the coatings. Therefore, in addition to monitoring the antimicrobial effect of silver doped HA and calcium hydroxide coatings, we also demonstrate that IMC might be a valuable tool for assessing such antimicrobial properties of implant coatings at a minimal workload.
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Antibacterianos , Hidróxido de Cálcio , Materiais Revestidos Biocompatíveis , Durapatita , Próteses e Implantes/microbiologia , Prata , Staphylococcus aureus/crescimento & desenvolvimento , Antibacterianos/química , Antibacterianos/farmacologia , Hidróxido de Cálcio/química , Hidróxido de Cálcio/farmacologia , Calorimetria/métodos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Durapatita/química , Durapatita/farmacologia , Prata/química , Prata/farmacologiaRESUMO
While calcium phosphate-based ceramics are currently the most widely used materials in bone repair, they generally lack tensile strength for initial load bearing. Bulk titanium is the gold standard of metallic implant materials, but does not match the mechanical properties of the surrounding bone, potentially leading to problems of fixation and bone resorption. As an alternative, nickel-titanium alloys possess a unique combination of mechanical properties including a relatively low elastic modulus, pseudoelasticity, and high damping capacity, matching the properties of bone better than any other metallic material. With the ultimate goal of fabricating porous implants for spinal, orthopedic and dental applications, nickel-titanium substrates were fabricated by means of selective laser melting. The response of human mesenchymal stromal cells to the nickel-titanium substrates was compared to mesenchymal stromal cells cultured on clinically used titanium. Selective laser melted titanium as well as surface-treated nickel-titanium and titanium served as controls. Mesenchymal stromal cells had similar proliferation rates when cultured on selective laser melted nickel-titanium, clinically used titanium, or controls. Osteogenic differentiation was similar for mesenchymal stromal cells cultured on the selected materials, as indicated by similar gene expression levels of bone sialoprotein and osteocalcin. Mesenchymal stromal cells seeded and cultured on porous three-dimensional selective laser melted nickel-titanium scaffolds homogeneously colonized the scaffold, and following osteogenic induction, filled the scaffold's pore volume with extracellular matrix. The combination of bone-related mechanical properties of selective laser melted nickel-titanium with its cytocompatibility and support of osteogenic differentiation of mesenchymal stromal cells highlights its potential as a superior bone substitute as compared to clinically used titanium.
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BACKGROUND: All-inside arthroscopic meniscal repairs are favored by most clinicians because of their lower complication rate and decreased morbidity compared with inside-out techniques. Until now, only 1000 cycles have been used for biomechanical testing. HYPOTHESIS: All-inside meniscal repairs will show inferior biomechanical response to cyclic loading (up to 100,000 cycles) and load-to-failure testing compared with inside-out suture controls. STUDY DESIGN: Controlled laboratory study. METHODS: Bucket-handle tears in 72 porcine menisci were repaired using the Omnispan and Fast-Fix 360 (all-inside devices) and Orthocord 2-0 and Ultrabraid 2-0 sutures (matched controls). Initial displacement, displacement after cyclic loading (100, 500, 1000, 2000, 5000, 10,000, and 100,000 cycles) between 5 and 20 N, ultimate load to failure, and mode of failure were recorded, as well as stiffness. RESULTS: Initial displacement and displacement after cyclic loading were not different between the groups. The Omnispan repair demonstrated the highest load-to-failure force (mean ± SD, 151.3 ± 21.5 N) and was significantly stronger than all the other constructs (Orthocord 2-0, 105.5 ± 20.4 N; Ultrabraid 2-0, 93.4 ± 22.5 N; Fast-Fix 360, 76.6 ± 14.2 N) (P < .0001 for all). The Orthocord vertical inside-out mattress repair was significantly stronger than the Fast-Fix 360 repair (P = .003). The Omnispan (30.8 ± 3.5 N/mm) showed significantly higher stiffness compared with the Ultrabraid 2-0 (22.9 ± 6.9 N/mm, P < .0001) and Fast-Fix 360 (23.7 ± 3.9 N/mm, P = .001). The predominant mode of failure was suture failure. CONCLUSION: All-inside meniscal devices show comparable biomechanical properties compared with inside-out suture repair in cyclic loading, even after 100,000 cycles. CLINICAL RELEVANCE: Eight to 10 weeks of rehabilitation might not pose a problem for all repairs in this worst-case scenario.
Assuntos
Meniscos Tibiais/cirurgia , Procedimentos Ortopédicos/instrumentação , Técnicas de Sutura , Animais , Fenômenos Biomecânicos , Teste de Materiais , Distribuição Aleatória , Estresse Mecânico , Suínos , Lesões do Menisco TibialRESUMO
Appropriate mechanical stimulation of bony tissue enhances osseointegration of load-bearing implants. Uniaxial compression of porous implants locally results in tensile and compressive strains. Their experimental determination is the objective of this study. Selective laser melting is applied to produce open-porous NiTi scaffolds of cubic units. To measure displacement and strain fields within the compressed scaffold, the authors took advantage of synchrotron radiation-based micro computed tomography during temperature increase and non-rigid three-dimensional data registration. Uniaxial scaffold compression of 6% led to local compressive and tensile strains of up to 15%. The experiments validate modeling by means of the finite element method. Increasing the temperature during the tomography experiment from 15 to 37°C at a rate of 4 K h(-1), one can locally identify the phase transition from martensite to austenite. It starts at ≈ 24°C on the scaffolds bottom, proceeds up towards the top and terminates at ≈ 34°C on the periphery of the scaffold. The results allow not only design optimization of the scaffold architecture, but also estimation of maximal displacements before cracks are initiated and of optimized mechanical stimuli around porous metallic load-bearing implants within the physiological temperature range.