Technological advances and economic trends are shaping the
MSCs (mesenchymal stem cells) are bone marrow-derived cells capable of replication and differentiation
In order to evaluate the feasibility of zinc alloys as future biodegradable bone implant materials, the mechanical properties, corrosion resistance, hemocompatibility, cell activity, proliferation and adhesion,
Graphene is a two-dimensional structure that is made of a single-atom-thick sheet of carbon atoms organised in hexagonal shapes. It is considered to be the mother of all graphite or carbon-based structures. It has shown exceptional physical and chemical properties which possess potential future applications. Graphene has an elasticity index similar to rubber and a hundred times tensile strength of steel and is even sturdier than diamonds. It is a very efficient biosensor with its exceptional electronic conductivity far greater than even copper. It is a potential future low cost material and its scalable production ability makes it even more attractive. The rediscovery of Graphene in 2008 saw few potential medical applications, specifically in the field of drug delivery, gene and cancer therapy. Nao graphene has extensive thermal conductivity and reflexivity, which can conceivably change imaging especially muskeloskeletal imaging and notably as a contrast material. It has been found to be a safe and a cheaper IV contrast agent in USA in 2012. Being an efficient biosensor especially in conducting electricity, it could assist in prosthetic and bionic limbs or prosthesis. Its durable stubborn properties, a composition which exceeds the strength of steel and light weight structure may create a potential material to develop into a new generation of a low profile internal fixing devices like plats. Most importantly, its scaffolding cell culturing assets could change the whole concept of prosthesis from mechanical press fit fixation to more dependence on bio adhesiveness.
In order to improve fast osseointegration, to modulate inflammatory response and to avoid biofilm formation, several attempts of surface modifications of titanium alloy in term of surface topography and chemistry have been performed over years, but this is still an open issue. In our research work, a patented chemical treatment was developed and tailored to improve fast osseointegration and to allow further surface functionalization in order to get a multifunctional surface. After the chemical treatment, Ti6Al4V shows a micro and nano-textured surface oxide layer with high density of hydroxyls groups, as summarized Figure 1: it is able to induce apatite precipitation (during soaking in Simulated Body Fluid), high wettability by blood, specific protein adsorption, positive osteoblast response and surface mechanical resistance to implantation friction. Hydroxyl groups exposed by the treated surface also allow binding natural biomolecules such as polyphenols, which can further improve the rate and quality of osseointegration by adding anti-inflammatory, antibacterial and antitumoral effects suitable for implants in critical situations. Polyphenols have the further added value of being a low cost and eco-sustainable product, extractable from byproducts of wine and food industry. On the chemically treated and functionalized samples, the surface characterization was performed using Folin&Ciocalteu test, fluorescence microscopy and XPS analysis in order to check the presence and activity of the grafted biomolecules (polyphenols from red grape pomace and green tea leaves). Cell tests were performed with Kusa A-1 cells highlighting the ability of polyphenols to improve osteoblasts differentiation and deposition of mineralized extracellular matrix. Surface functionalization can also be performed with chitin derived biomolecules to reduce inflammation. With the purpose of obtaining the antibacterial effect, during the chemical treatment a silver precursor can also be added to obtain in situ reduced silver nanoparticles embedded in the nano-structured oxide layer. The samples containing nanoparticles on the surface were characterized by means of TEM and FESEM observation highlighting the presence of well distributed and small-sized nanoparticles on the surface and through the thickness of the oxide layer. A long-lasting release in water was observed up to 14 days and antibacterial tests on Staphylococcus aureus showed the ability of the surface to reduce bacteria viability avoiding biofilm formation. The results showed that the patented chemical treatment can improve the response of osteoblasts to titanium alloy implants, but is also a promising way to obtain multifunctional surfaces with antibacterial, antioxidant, anti-inflammatory and antitumoral properties that can be the
Musculoskeletal (MSK) disorders continue to be a major cause of pain and disability worldwide. The mission statement of the Canadian Orthopaedic Association (COA) is to “promote excellence in orthopaedic and musculoskeletal health for Canadians,” and orthopaedic surgeons serve as leaders in addressing and improving musculoskeletal health. However, patients with MSK complaints most commonly present first to a primary care physician. According to a survey of family physicians in British Columbia, 13.7-27.8% of patients present with a chief complaint that is MSK-related (Pinney et Regan, 2001). Therefore, providing excellent MSK care to Canadians requires that all physicians, especially those involved in primary care, be adequately trained to diagnose and treat common MSK conditions. To date, there has been no assessment of the total mandatory MSK training Canadian family medicine residents receive. It is also unclear, despite the prevalence of MSK complaints among Canadian patients, if current family physicians are competent or confident in their ability to provide fundamental MSK care. The purpose of this study is to determine the amount of mandatory MSK training Canadian family medicine residents are currently receiving. Web-based research was used to determine how many weeks of mandatory MSK training was incorporated into current Canadian family medicine residency training programs. This information was gathered from either the Canadian Resident Matching Service website (carms.ca) or the residency program's individual website. If this information was not available on a program's website, a program administrator was contacted via email in order to ascertain this information directly. MSK training was considered to be any rotation in orthopaedic surgery, spine surgery, sports medicine, or physiatry. 156 Canadian family medicine residency training sites were identified. Information pertaining to mandatory MSK education was collected for 150 sites (95.5%). Of the 150 training sites, 102(68 %) did not incorporate any mandatory MSK training into their curriculum. Of the 48 programs that did, the average number of weeks of MSK training was 3.37 weeks. 32/48 programs (66.7%) included 4 weeks of MSK training, which represents 3.8% of a 2-year training program. Current Canadian family medicine residents are not receiving sufficient musculoskeletal training when compared to the overall frequency of musculoskeletal presentations in the primary care setting. Understanding current family medicine physicians’ surveyed confidence and measured competence with respect to diagnosing and treating common musculoskeletal disorders could also prove helpful in demonstrating the need for increased musculoskeletal education.
Prosthetic joint infections represent complications connected to the implantation of biomedical devices. Bacterial biofilm is one of the main issues causing infections from contaminated orthopaedic prostheses. Biofilm is a structured community of microbial cells that are firmly attached to a surface and have unique metabolic and physiological attributes that induce improved resistance to environmental stresses including toxic compounds like antimicrobial molecules (e.g. antibiotics). Therefore, there is increasing need to develop methods/treatments exerting antibacterial activities not only against planktonic (suspended) cells but also against adherent cells of pathogenic microorganisms forming biofilms. In this context, metal-based coatings with antibacterial activities have been widely investigated and used in the clinical practice. However, traditional coatings exhibit some drawbacks related to the insufficient adhesion to the substrate, scarce uniformity and scarce control over the toxic metal release reducing the biofilm formation prevention efficacy. Additionally, standardized and systematic approaches to test antibacterial activity of newly developed coatings are still missing, while standard microbiological tests (e.g. soft-agar assays) are typically used that are limited in terms of simultaneous conditions that can be tested, potentially leading to scarce reproducibility and reliability of the results. In this work, we combined the Calgary Biofilm Device (CBD) as a device for high-throughput screening, together with a novel plasma-assisted technique named Ionized Jet Deposition (IJD), to generate and test new generation of nanostructured silver- and zinc-based films as coatings for biomedical devices with antibacterial and antibiofilm properties. During the experiments we tested both planktonic and biofilm growth of four bacterial strains, two gram-positive and two gram-negative bacterial strains, i.e. Staphylococcus aureus ATCC 6538P, Enterococcus faecalis DP1122 and Escherichia coli ATCC 8739 and Pseudomonas aeruginosa PAO1, respectively. The use of CBD that had the only wells covered with the metal coatings while the biofilm supports (pegs) were not sheltered allowed to selectively define the toxic effect of the metal release (from the coating) against biofilm development in addition to the toxic activity exerted by contact killing mechanism (on biofilms formed on the coating). The results indicated that the antibacterial and antibiofilm effects of the metal coatings was at least partly gram staining dependent. Indeed, Gram negative bacterial strains showed high sensitivity toward silver in both planktonic growth and biofilm formation, whereas zinc coatings provided a significant inhibitory activity against Gram positive bacterial strains. Furthermore, the coatings showed the maximal activity against biofilms directly forming on them, although, Zn coating showed a strong effect against biofilms of gram-positive bacteria also formed on uncoated pegs. We conclude that the metal-based coatings newly developed and screened in this work are efficient against bacterial growth and adherence opening possible
This study aimed to determine the major diagnoses and needs of children in Rwanda with musculoskeletal conditions to enable the Rwandan government to begin to plan orthopaedic and rehabilitation services. BACKGROUND. When faced with developing orthopaedic services for children in Sub-Saharan Africa, there is little objective evidence-based data on the magnitude and type of services needed. Rwanda is a small country that is in the process of developing orthopaedic and rehabilitation services, and its Ministry of Health supported a survey that would provide information necessary for planning such services. METHODS. A national survey of musculoskeletal impairment (MSI) prevalence was undertaken. Of a population of 8.4 million, 8368 people were enumerated. Four thousand one hundred thirty-four were aged 16 years or less. Cases who failed a screening test for MSI were examined, allocated a diagnostic category, and assessed as to treatment needed. RESULTS. Of 4134 people aged 16 years or less who were enumerated, 3526 (85%) were screened and 91 had MSI, giving a prevalence of MSI among children of 2.58% (95% confidence interval; 2.06-3.10). Twenty-three percent of MSIs were a result of congenital deformity, 14% neurologic conditions, 12% trauma, 3% infection, and 46% other acquired pathology. Of the MSIs, 56.7% were mild, 37.8% moderate, and 5.6% severe. Extrapolated treatment needs suggest that 2% of Rwandan children (approximately 80,000) need orthopaedic physical therapy, 1.2% (50,000) need orthopaedic surgery, and approximately 10,000 need orthopaedic appliances. CONCLUSIONS. These results will be of use in planning
Since 2010, there has been a sharp decline in the use of metal-on-metal joint replacement devices due to adverse responses associated with the release of metal wear particles and ions in patients. Surface engineered coatings offer an innovative solution to this problem by covering metal implant surfaces with biocompatible and wear resistant materials. The present study tests the hypothesis whether surface engineered coatings can reduce the overall biological impact of a device by investigating recently introduced silicon nitride coatings for joint replacements. Biological responses of peripheral blood mononuclear cells (PBMNCs) to Si3N4 model particles, SiNx coating wear particles and CoCr wear particles were evaluated by testing cytotoxicity, inflammatory cytokine release, oxidative stress and genotoxicity. Clinically relevant wear particles were generated from SiNx-on-SiNx and CoCr-on-CoCr bearing combinations using a multidirectional pin-on-plate tribometer. All particles were heat treated at 180°C for 4 h to destroy endotoxin contamination. Whole peripheral blood was collected from healthy donors (ethics approval BIOSCI 10–108, University of Leeds). The PBMNCs were isolated using Lymphoprep (Stemcell) and incubated with particles at various volumetric concentrations (0.5 to 100 µm3 particles/cell) for 24 h in 5% (v/v) CO2 at 37°C. After incubation, cell viability was measured using the ATPlite assay (Perkin Elmer); TNF-alpha release was measured by ELISA (Invitrogen); oxidative stress was measured using H2DCFDA (Abcam); and DNA damage was measured by comet assay (Tevigen). The results were expressed as mean ± 95% confidence limits and the data was analysed using one-way ANOVA and Tukey-Kramer post-hoc analysis. No evidence of cytotoxicity, oxidative stress, TNF-alpha release, or DNA damage was observed for the silicon nitride particles at any of the doses. However, CoCr wear particles caused cytotoxicity, oxidative stress, TNF-alpha release and DNA damage in PBMNCs at high doses (50 µm3 particles per cell). This study has demonstrated the in-vitro biocompatibility of SiNx coatings with primary human monocytic cells. Therefore, surface engineered coatings have potential to significantly reduce the biological impact of metal components in
It is well established that cell behaviour is responsive to the surrounding environment. Chemistry, material stiffness and topography allow control of cell adhesion, proliferation, growth and differentiation. Biomimicry is playing a role in the next generation of biomaterials, surface engineering on orthopaedic implants may promote improved skeletal integration. Human osteoblasts were cultured on engineered micro-topographical features with nanoscale depths, similar in scale to an osteoclast resorption pit. Three different micro-topographies were used (in addition to planar controls.) created on a hot moulded polymer. The cells were cultured in basal media on surfaces with 20, 30 and 40 micrometer circular pits, each with a depth of 400 nanometers. The cells were fixed at time points 3 days, 21 days and 28 days to allow assessment of cytoskeletal development, production of protein markers of bone production (osteopontin) and mineral deposition respectively. At each time point greater indicators of cell activity and bone production were evident on the 30 and 40 micrometer structures as compared with the 20 micrometer structures and the planar controls. These positive results include increased focal adhesions, stronger expression of intracellular and extracellular osteopontin and more mature nodules of calcium formation. This in vitro study demonstrates that micro and nanotopographies influence cell activity. Osteoblast response can be induced on the surface of a
It has been shown that mesenchymal stem cells (MSCs) and BMP are involved in bone formation. The aim of the study was to evaluate the osteogenic potential of human bone marrow (hBM), human expanded MSC (hexp-MSC), BMP-7, and hexp-MSC plus BMP-7, to treat a rat femoral segmental defect. Sprague-Dawley (SD) and athymic rats (Nu) were used. SD rats where used in order to define surgical technique. Nu rats groups consisted of: G1-autoclaved bone and human bone marrow (hMNC); G2-bone and hexp-MSC; G3-bone with BMP-7 only; and G4-bone and hexp-MSC with BMP-7. A plate was attached to the femoral diaphysis with two cerclage wires. Then a 6-mm femoral gap was made and filled with a different graft. At regular intervals, the femoral defect was evaluated with radiographs, using a modified six-grade Cook classification. At 8 weeks G1 showed non-visible new bone formation; G2 minimal new disorganised bone; G3 disorganised new bone bridging the graft to host at both ends; and G4 significant new bone and graft remodelling. Histological analysis confirmed these results. Our results showed that although the osteogenic activity may be improved by hMSC (G2) as well as by BMP-7 (G3), the association hexp-MSC plus BMP-7(G4) produced graft osteointegration at 8 weeks after surgery. This may have a remarkable impact on
Objective: To point out the strict rules of surgical technique required for the success of newly applied advanced technology. Materials: 73 hips in 70 patients, aged 23 to 71 years old, underwent total hip arthroplasty using ceramic bearing surfaces implants. 62 were a primary procedure, and 11 were revision surgery. Results: One complication of fracture of posterior ace-tabular wall was registered in a patient with ankylosing spondylitis, four early dislocations that were reduced closed, and one case of late postoperative death in a cardiac high-risk patient. No other complications were recorded since the first operation in May 1999. All patients had remarkable pain relief, improved range of motion and improved function. Discussion: The tribological properties of the ceramic articulating surfaces favors them as the preferred technology for
With the recent reductions in junior doctor hours levels of staffing have become ever more critical as clinical duties are covered with fewer junior doctors available on a daily basis. Trainees also have to meet specific requirements of the curriculum and thus need to be allocated to posts with suitable opportunities. There is little evidence available to account for the allocation of posts to individual trusts and departments with training post numbers seem driven by historical allocation, rather than based on trainee and local population needs. ‘SHO’ tier numbers were obtained for each orthopaedic department within the Yorkshire deanery through direct contact with the departments. Data was also obtained to establish the workload of these departments. Information was gathered from the national neck of femur database, hospital episode statistics, the national joint registry, the trauma audit and research network (TARN) and finally Dr Foster and the national census. The workload data was then analysed and compared to the staffing levels in each department. Data was obtained for fourteen trusts across the Yorkshire Deanery. The percentage of SHO tier doctors in training posts ranged from 0 to 78% (mean 37%) across the trusts surveyed, with wide variation in make up of the SHO tier in each department. Workload was standardised using the unit of cases/SHO/annum. The workload for neck of femur fractures ranged from 8 to 52 cases/SHO/annum (mean 36). General trauma admissions ranged from 199 to 383 cases/SHO/annum (mean 288). Elective arthroplasty admissions ranged from 11 to 174 (mean 70). Pearson correlation coefficients were 0.5 for elective arthroplasty and neck of femur admissions and 0.8 for trauma admissions. There is wide variation in workload between trusts when standardised for the number of SHO's with weak to moderate correlations between the number of juniors and workload in each department. This wide variation will impact on patient care, but also the training opportunities available in different posts – where workload is higher it is likely there will be an increased need for ward based work away from clinics and theatre lists. The introduction of the foundation programme and MMC has changed the structure of the SHO grade at a time when the EWTD introduction has also had a profound impact on working patterns and hours. At this time we believe there is a need for a review of trainee allocations nationally with comparison to workload in each trust, trainee logbook data and data on curriculum competencies met. With the proposed reductions in trainee numbers now is the time for a centrally led review of these posts via the Royal College, BOA and BOTA to ensure high quality training, maintain high standards of patient care and secure the
When investigating orthopaedic biomaterials and tissue engineered devices, biological investigations by means of in vitro and in vivo tests are mandatory to obtain a overall picture of biocompatibility and therapeutic efficacy. However, various aspects requiring careful consideration should be kept in mind and can explain the complex situations encountered by researchers when the skeletal tissue is involved. This presentation aimed to summarize some useful information in improving in vivo methodology to test present and
Summary. Aim of this study is to design, develop and preclinical test PET nanostructured scaffolds for the transplantation and differentiation of MSCs in the treatment of bone defects. The interaction of cells with nanotopographical features has proven to be an important signaling modality in controlling MSC differentiation. Introduction. The wide bone defects, caused by trauma, tumor, infectious, periprosthetic osteolysis, need to be surgically treated because their low potential of repair. Nowadays the bone allograft and autograft represent 80% of all transplantation done in the world. However this technique shows many disadvantages, such as the risk of infections, the immunological rejection, the low bone availability and the high costs. These reasons have motivated extensive research to find alternative strategies. As shown in literature, the future strategies are based on the synergic combination of different methodologies: use of biomimetic scaffold in order to support bone regeneration, use of mesenchymal stromal cells (MSCs) and growth factors. Successful regeneration necessitates the development of tissue-inducing scaffolds that mimic the hierarchical architecture of native tissue extracellular matrix (ECM). Cells in nature recognise and interact with the surface topography they are exposed to via ECM proteins. Here we are going to show the guidelines recently published for the design and development of nanostructured scaffolds for the bone regeneration, and the morphofunctional changing of MSCs interacting with nanogratings. Methods. Aim of this study is to design, develop and preclinical test PET nanostructured scaffolds for the transplantation and differentiation of MSCs in the treatment of bone defects. The first step of our study was the extraction of patient's bone marrow and the isolation of MSCs. After characterizing (demonstrating the typical cell surface markers) and isolating the MSCs were cultivated on the PET substrates. The PET nanosubstrates were obtained by a low temperature embossing lithography (HEL) achieving low-damage nanotopographic surface modifications. After MSC cultivation on PET substrates we made a cytotoxicity evaluation, an optic and confocal microscopic evaluation (cells adhesion, cells polarization…) and tests to optimise cell differentiation towards osteogenic fate. Results. PET is a highly suitable thermo-plastic material, able to sustain the necessary methods to obtain nanostructured substrates. MSCs cultivated on nanostructured PET rapidly align with the direction of the nanostructure itself without any cytotoxic effects. After the cultivation on the nanostructures, MSCs sustained cytoskeleton changes suggesting the activation of intracellular signaling (mechanotrasduction) promoting osteogenesis. Discussion. The mechanisms by which nanotopographic cues influence stem cell proliferation and differentiation appear to involve changes in cytoskeletal organization and structure, potentially in response to the geometry and size of the underlying features of the ECM by a process called mechanotrasduction. The interaction of cells with nanotopographical features such as pores, ridges, groves, fibers, nodes, and their combinations has proven to be an important signaling modality in controlling cellular processes. Integrating nanotopographical cues is especially important in engineering complex tissues that have multiple cell types and require precisely defined cell-cell and cell-matrix interactions at the nanoscale. Thus, in the next-generation regenerative engineering approaches, nanoscale materials/scaffolds are expected to play a parimary role in controlling MSC fate and the consequent regenerative capacity. We believe that the continuous development of nanotechnology and deeply comprehension of how mechanical inputs can affect cell biology is fundamental to design the
Introduction: Minimal invasive surgery (MIS) seems to be part of
Background: The use of fresh morsellised allograft in impaction bone grafting for revision hip surgery remains the gold standard. Bone marrow contains osteogenic progenitor cells that arise from multipotent mesenchymal stem cells and we propose that in combination with allograft will produce a living composite with biological and mechanical potential. This study aimed to determine if human bone marrow stromal cells (HBMSC) seeded onto highly washed morsellised allograft could survive the impaction process, differentiate and proliferate along the osteogenic lineage and confer biomechanical advantage in comparison to impacted allograft alone. Methods: HBMSC were isolated and culture expanded in vitro under osteogenic conditions. Cells were seeded onto prepared morsellised allograft and impacted with a force equivalent to a standard femoral impaction (474J/m2). Samples were incubated for either two or four week periods under osteogenic conditions and analysed for cell viability, histology, immunohistochemistry, and biochemical analysis of cell number and osteogenic enzyme activity. Mechanical shear testing, using a Cam shear tester was performed, under three physiological compressive stresses (50N, 150N, 250N) from which the shear strength, internal friction angle and particle interlocking values were derived. Results: Cell viability of HBMSC post impaction, was confirmed with cell tracker green staining, a marker of viable cells, and observed throughout all samples. There was a significant increase in DNA content and specific alkaline phosphatase activity compared to impacted seeded allograft samples. Immunohistochemical staining for type I collagen confirmed cell differentiation along the osteogenic lineage. Mechanical shear testing demonstrated a statistical significant increase in shear strength and interparticulate cohesion in the allograft/hBMSC group over allograft alone at 2 and 4 week intervals (p<
0.001). Conclusion: HBMSC seeded onto allograft resulted in the formation of a living composite capable of withstanding the forces equivalent to a standard femoral impaction. HBMSC under osteogenic conditions were observed to differentiate and proliferate along the osteogenic lineage. In addition, an allograft/HBMSC living composite confers a biomechanical advantage over allograft alone These changes resulting in enhancement of biological and mechanical properties of bone graft within impaction bone grafting have implications for translation and
Introduction: Distraction osteogenesis has been used as a method of generating new bone in limb lengthening and deformity realignment; and is achieved in our unit though the use of the Sheffield Ring Fixator. The development of soft tissue tension creates an entirely different mechanical environment, and can often result in severe complications during treatment. Fixators must therefore be able to resist these forces. Furthermore, biomechanical modelling is very different from fracture and bone gap simulation. The model developed in this study intended to look at linear distraction, i.e. lengthening. Aims: To create a mechanical model that simulates the soft tissue effects during lengthening with an external fixator. To obtain a synthetic material with similar passive tensile properties to that measured in lengthened soft tissue. To measure the effect of tensioned synthetic soft tissue on osteotomy motion and multi-planar stiffness during cyclic loading. Materials and Methods: A standard two 150mm ring frame was mounted on an acrylic rod, with a centrally placed osteotomy gap of 75mm. One ring was fixed with wires and the other with screws. An inter-fragmentary motion device was attached across the osteotomy, to measure axial, angular and shear deformation with both axial and off-axis loading. Soft tissue tension was simulated with the use of neoprene rubber sheeting, attached to the nylon rod by Jubilee clips, with a gap anteriorly or medially. Extensive tensile testing was performed to determine the visco-elastic behaviour of the rubber, which showed it to be consistent and reliable. Tension of a similar magnitude to lengthened muscle (35–125N) was achieved, and could be accurately predicted for certain distraction lengths. The stiffness of the frame was calculated from osteotomy motion with various distraction lengths both with the rubber attached and without. Results: Tension in the soft tissues summates with the force applied in loading, with the effect of increasing the axial stiffness of the fixator by up to 70N, with a directly proportional relationship. It also acts as a restraint for shear and angulatory motion. In anterior and lateral loading positions however, the angulation stiffness remains low; this is thought to be due to the unequal distribution of soft tissues around the bony column, as seen in vivo. The stiffness of the frame is lowered by increasing the distance between rings; this effect can be counteracted by soft tissue tension in axial stiffness, but less so for angular and shear. Conclusions: We conclude that osteotomy stability is dependent on soft tissue tension, and the magnitude of tension greatly alters the stiffness characteristics of the external fixator. This study highlights the important role of soft tissue tension in biomechanical modelling and clinical limb lengthening, and has exciting ramifications for
