Technological advances and economic trends are shaping the future of orthopaedics, where a clinical solution encompasses all phases of surgery. Minimally invasive surgery (MIS) continues to become more popular and important in modern-day orthopaedics, but brings added complexity to the operating room. Computer assisted surgery (CAS) has the potential to provide greater reliability, repeatability, and control to orthopedic surgeries, although limitations in the technologies currently available for minimally invasive CAS procedures leave much to be desired. Despite new techniques and modern technologies, improvements are needed to achieve consistency of optimal patient outcomes in orthopaedic surgery. Healthcare markets are moving to emphasize the value of patient-specific intervention with reliable, custom solutions. We are developing a framework for orthopedic CAS which utilizes new technologies and a cohesive approach in providing a robust solution for the future of orthopaedics. Through the use of surgical preplanning, intra-operative guidance, and post-operative gait analysis, a full analysis and design cycle is used to ensure optimal patient outcome by focusing on the combination of the three surgical phases. In order to realize this comprehensive framework, a system-level design approach combined with cutting-edge technology is needed, catering to patient-specific anatomical reconstruction. In the pre-operative phase, X-ray images are used in the 3-D reconstruction of patient-specific models of the targeted anatomy. This is combined with automated morphometric measurements to provide automatic cutting plane alignment and a complete design suite for patient-specific implants. In the intraoperative phase, new wireless navigation technologies provide robust performance where optical and electromagnetic tracking systems fall short. MEMS capacitive sensor array technology provides accurate and real-time pressure sensing feedback for ligament balancing, and new software frameworks virtualize surgical protocols. Extensive gait analysis including X-ray fluoroscopy provides 3-D kinematic data in the post-operative phase to provide valuable feedback on implant performance for improved implant design

MSCs (mesenchymal stem cells) are bone marrow-derived cells capable of replication and differentiation in-vitro into several tissues including bone, cartilage, stroma, fat, muscle and tendon. MSCs can be isolated by relatively simple procedures and then expanded without losing the ability to differentiate into multiple lineages. As such, these cells have immense clinical potential in regenerative medicine and in orthopaedics for repair or replacement of damaged tissues. In this work we investigated the interaction between magnetic carbon nanotubes (CNTs) and MSCs and their ability to guide these cells injected intravenously in living mice by using an external magnetic field. CNTs did not affect cell viability and their ability to differentiate. Both the CNTs and the magnetic field did not alter cell growth rate, phenotype and cytoskeletal conformation. CNTs, when exposed to magnetic fields, are able to shepherd MSCs towards the magnetic source in vitro. Moreover, the application of a magnetic field alters the biodistribution of CNT-labelled MSCs after intravenous injection into rats. We demonstrated that CNTs hold the potential for use as nano-devices to improve therapeutic protocols for transplantation and homing of stem cells in vivo. This could pave the way for the development of new strategies for manipulation/guidance of MSCs in regenerative medicine and cell transplantation for the treatment of many orthopaedic diseases.

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, in vivo animal implantation experiments have been employed. The experimental results show that the alloying element magnesium, calcium and strontium can significantly improve the mechanical properties of pure zinc, and further deformation processes can further improve the mechanical properties of zinc alloys. Alloying elements can effectively control the corrosion rates of zinc alloys, which are between the rates of magnesium alloys and iron alloys. Zinc and zinc alloys exhibit excellent hemocompatibility and the hemolysis rate is far lower than 5%. After adding alloying elements Mg, Ca and Sr, MG63 and ECV304 cell proliferation rate and activity increased significantly, while for VSMC cell, the influence of alloying elements effect is not obvious. Zinc alloy intramedullary pins can effectively promote the new bone formation, and after 2 months implanted in mice femur, they still maintained a relatively complete structure, indicating that they are able to provide enough mechanical strength and thus more conducive to bone tissue repair and healing.

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 future of orthopedic implants

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. Future orthopaedic initiatives could help enhance family medicine MSK training

Little is known about the incidence of rotator cuff pathology or its demographic associations in the general population. We undertook a large epidemiological study of rotator cuff pathology in the United Kingdom using The Health Improvement Network (THIN) database. The incidence of rotator cuff pathology was 87 per 100 000 person-years. It was more common in women than in men (90 cases per 100 000 person-years in women and 83 per 100 000 person-years in men; p < 0.001). The highest incidence of 198 per 100 000 person-years was found in those aged between 55 and 59 years. The regional distribution of incidence demonstrated an even spread across 13 UK health authorities except Wales, where the incidence was significantly higher (122 per 100 000 person-years; p < 0.001). The lowest socioeconomic group had the highest incidence (98 per 100 000 person-years). The incidence has risen fourfold since 1987 and as of 2006 shows no signs of plateauing. This study represents the largest general population study of rotator cuff pathology reported to date. The results obtained provide an enhanced appreciation of the epidemiology of rotator cuff pathology and may help to direct future upper limb orthopaedic services. Cite this article: Bone Joint J 2014;96-B:350–3

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 future applications for orthopedic protheses manufacturing

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 future paediatric orthopaedic services in Rwanda, and for comparative studies in other low-income countries

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 future orthopaedic devices

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 future generation of orthopaedic implants, lasting long after the effects chemical application have expired. Further research is required to assess the potential application to implant grade materials

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 future orthopaedics surgery strategies

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 future orthopaedic implants. By reducing wear to a minimum the choice of ceramics seems to be justified. The main concern is fragility versus toughness. We have formulated ten rules of proper surgical technique concerning: accurate fit of the components, accurate orientation of the components, stability of the joints, adequate tissue tension, caring for debris and prevention of metal transfer due to ceramic-metal touch. Conclusions: While our clinical experience is still short term, it appears that applying a rigorous and uncompromising surgical technique with ceramic bearing surfaces is essential for the clinical success of this potent bio-material. Based on our experience, our recommendations are that:. Ceramic bearing surfaces T.H.A.-s should be performed in specialized centers. The use of 32 mm. heads should be considered in order to avoid dislocations. With 28 mm. heads, full profile cups should be considered. Conservative physical therapy and range of motion exercises for 6–12 weeks

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 future of the orthopaedic profession

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 future therapies for orthopaedic surgery. Some in vivo biological tests to study innovative reconstructive surgical techniques are summarized on the basis of the experience of the Experimental Surgery Department –IOR. After in vitro and in vivo biocompatibility tests, for the study of bone defect healing and of biomaterial osteo-inductive properties the subcutaneous and intramuscular implants are usually performed in laboratory animals while osteoconduction and bone healing evaluation require the development of “nonunions” (sites that never achieve functional bone continuity) and “critical size defects” (the smallest defect that will heal with less than 10% bony growth) models. Biomaterial osteointegration properties are investigated by means of metaphyseal, diaphyseal and intramedullary implantation. The use of pathological animals is also recommended to take into account the clinical situation where biomaterials are often implanted in aged and osteoporotic patients. As far as articular cartilage pathology is concerned, chondral and osteochondral “critical size defects” may be performed and the development of osteoarthritic animals could be also useful. At different experimental times post-explantation evaluations by means of radiology, histology, histomorphometry and biomechanics provide a complete characterization of biomaterials and biotechnologies showing their potential therapeutic efficacy for skeletal reconstruction. In vivo studies provide important pre-clinical information on new biomaterials and biotechnologies for the skeletal reconstruction Among the factors that are increasingly improving the reliability of in vivo testing are the continuous improvement in knowledge on bone biology and comparative science between humans and animals, the awareness that animal suffering should be reduced as much as possible, and, finally, the amount and the accuracy of in vivo post-explantation findings

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 future scaffold for orthopedic application