Knee swelling is common after injury or surgery, resulting in pain, restricted range of movement and limited mobility. Accurately measuring knee swelling is critical to assess recovery. However, current measurement methods are either unreliable or expensive [1,2]. Therefore, a new measurement method is developed. This wearable (the ‘smart brace’) has shown the ability to distinguish a swollen knee from a not swollen knee using multi-frequency-bio impedance analysis (MF-BIA) [3]. This study aimed to determine the accuracy of this smart brace. The study involved 25 usable measurements on patients treated for unilateral knee osteoartritis with a 5mL injection of Lidocaïne + DepoMedrol (1:4). MF-BIA measurements were taken before and after the injection, both on the treated and untreated knee. The smart brace accurately measured the effect of the injection by a decrease in resistance of up to 2.6% at 100kHz (p<0.01), where commonly used gel electrodes were unable to measure the relative difference. Remarkably, both the smart brace and gel electrodes showed a time component in the MF-BIA measurements. To further investigate this time component, 10 participants were asked to lie down for 30 minutes, with measurements taken every 3 minutes using both gel electrodes and the smart brace on both legs. The relative change between each time step was calculated to determine changes over time. The results showed presence of a physiological aspect (settling of knee fluids), and for the brace also a mechanical aspect (skin-electrode interface) [4]. The mechanical aspect mainly interfered with reactance values. Overall, the smart brace is a feasible method for quantitatively measuring knee swelling as a relative change over time. However, the skin-electrode interface should be improved for reliable measurements at different moments in time. The findings suggest that the smart brace could be a promising tool for monitoring knee swelling during rehabilitation

Traumatic acute or chronic tendon injuries are a wide clinical problem in modern society, resulting in important economic burden to the health system and poor quality of life in patients. Due to the low cellularity and vascularity of tendon tissue the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Tissue engineering and regenerative medicine are promising alternatives to the natural healing process for tendon repair, especially in the reconstruction of large damaged tissues. The aim of TRITONE project is to develop a smart, bioactive implantable 3D printed scaffold, able to reproduce the structural and functional properties of human tendon, using FDA approved materials and starting from MSC and their precursor, MPC cell mixtures from human donors. Total cohort selected in the last 12 months was divided in group 1 (N=20) of subjects with tendon injury and group 2 (N=20) of healthy subject. Groups were profiled and age and gender matched. Inclusion criteria were age>18 years and presence of informed consent. Ongoing pregnancy, antihypertensive treatment, cardiovascular diseases, ongoing treatment with anti-aggregants, acetylsalicylic-acid or lithium and age<18 years were exclusion criteria. Firstly, we defined clinical, biological, nutritional life style and genetic profile of the cohort. The deficiency of certain nutrients and sex hormonal differences were correlated with tendon-injured patients. It was established the optimal amount of MPC/MSC human cell (collected from different patients during femoral neck osteotomy). Finally, most suitable biomaterials for tendon regeneration and polymer tendon-like structure were identified. Hyaluronic acid, chemical surface and soft-molecular imprinting (SOFT-MI) was used to functionalize the scaffold. These preliminary results are promising. It will be necessary to enroll many more patients to identify genetic status connected with the onset of tendinopathy. The functional and structural characterization of smart bioactive tendon in dynamic environment will represent the next project step

By definition, a smart biomaterial is a material, such as a ceramic, alloy, gel or polymer, that can convert energy from one form into another by responding to a change in a stimulus in its environment. These stimuli may involve temperature, pH, moisture, or electric and magnetic fields. In particular, thermoresponsive biomaterials have been successfully employed to host mammalian cells with a view to musculoskeletal tissue engineering. The presentation provides an overview of the use of thermosensitive polymers for the non-enzymatic stem cell harvesting, cell sheet engineering, three-dimensional scaffolds fabrications and organ-printing materials

Mesoporous bioactive glasses (MBGs) have been widely studied as bone regeneration systems, due to their bioactivity and ability to store and release therapeutic agents with specific biological functions. The incorporation of these nanomaterials into a thermosensitive hydrogel (TSH), in which a solution undergoes a sol-gel transition under physiological conditions, represents a promising approach to design multifunctional devices able to deliver selected molecules to pathological sites. In fact, this system can perfectly fit the defect cavity shape prior to the complete gelation, and acts as a carrier for therapeutic agents prolonged release in situ. This challenging concept is the underlying idea of the MOZART project, whose objective was to develop a library of MBGs containing different therapeutic ions and drugs, to be used as a new, smart platform technology for highly targeted therapies to enhance bone healing. The aim of this work is to investigate the bone regeneration potential of MBGs containing strontium ions (pro-osteogenic) and incorporated into thermosensitive poly(etherurethane)(PEU) based on Poloxamer407. In order to further increase the pro-osteogenic response, MBGs were also loaded with N-acetylcysteine (NAC). MBGs containing 2%mol of Sr. 2+. were prepared by an aerosol-assisted spray-drying method and NAC was loaded post-synthesis via an incipient wetness method. The PEU hydrogel (SHP407) was synthesized via a two-step procedure in nitrogen atmosphere. Particles were characterized (FE-SEM, N. 2. adsorption-desorption analysis, TGA, DSC, FT-IR and XRD) and then incorporated into the hydrogel. The hybrid systems rheological properties and stability in aqueous environment at 37°C, and its ability to co-release Sr. 2+. and NAC were analysed. After preliminary biological in vitro tests, a proof-of-concept rodent study was run to assess the ability of the resulting formulation as bone healing device. X-ray at 2 and 4-weeks post-surgery and µCT-analysis were used to evaluate the healing results in a rat osteotomy model of biologically impaired healing. Then, bones were processed for histological evaluation. Preliminary in vivo results demonstrated that incorporation of MBGs into a TSH is a promising strategy to design a multifunctional injectable formulation for in situ and sustained delivery of pro-osteogenic species enhancing bone regeneration

Access to health care, including physiotherapy, is increasingly occurring through virtual formats. At-home adherence to physical therapy programs is often poor and few tools exist to objectively measure low back physiotherapy exercise participation without the direct supervision of a medical professional. The aim of this study was to develop and evaluate the potential for performing automatic, unsupervised video-based monitoring of at-home low back physiotherapy exercises using a single mobile phone camera.

24 healthy adult subjects performed seven exercises based on the McKenzie low back physiotherapy program while being filmed with two smartphone cameras. Joint locations were automatically extracted using an open-source pose estimation framework. Engineered features were extracted from the joint location time series and used to train a support vector machine classifier (SVC). A convolutional neural network (CNN) was trained directly on the joint location time series data to classify exercises based on a recording from a single camera. The models were evaluated using a 5-fold cross validation approach, stratified by subject, with the class-balanced accuracy used as the performance metric.

Optimal performance was achieved when using a total of 12 pose estimation landmarks from the upper and lower body, with the SVC model achieving a classification accuracy of 96±4% and the CNN model an accuracy of 97±2%.

This study demonstrates the feasibility of using a smartphone camera and a supervised machine learning model to effectively assess at-home low back physiotherapy adherence. This approach could provide a low-cost, scalable method for tracking adherence to physical therapy exercise programs in a variety of settings.

Summary Statement

The purpose of this experimental imaging study is to determine the Poisson's ratio of ovine periosteum, using strain mapping data from an imaging study designed to elucidate the mechanical environment of periosteal progenitor cells in situ during stance shift loading.

Skeletal muscle tissue engineering has made progress towards production of functional tissues in line with the development in materials science and fabrication techniques. In particular, combining the specificity of 3D printing with smart materials has introduced a new concept called the 4D printing. Inspired by the unique properties of smart/responsive materials, we designed a bioink made of gelatin, a polymer with well-known cell compatibility, to be 3D printed on a magnetically responsive substrate. Gelatin was made photocrosslinkable by the methacrylate reaction (GELMA), and its viscosity was finetuned by blending with alginate which was later removed by alginate lyase treatment, so that the printability of the bioink as well as the cell viability can be finetuned. C2C12 mouse myoblasts-laden bioink was then 3D printed on a magnetic substrate for 4D shape-shifting. The magnetic substrate was produced using silicon rubber (EcoFlex) and carbonyl iron powders. After 3D printing, the bioink was crosslinked on the substrate, and the substrate was rolled with the help of a permanent magnet. Unrolled (Open) samples were used as the control group. The stiffness of the bioink matrix was found to be in the range of 13–45 kPa, which is the appropriate value for the adhesion of C2C12 cells. In the cell viability analysis, it was observed that the cells survived and could proliferate within the 7-day duration of the experiment. As a result of the immunofluorescence test, compared to the Open Group, more cell nuclei were observed overlapping MyoD1 expression in the Rolled Group; this indicated that the cells in these samples had more cell-cell interactions and therefore tended to form more myotubes. Acknowledgements: This research was supported by the TÜBİTAK 2211-A and YÖK 100/2000 scholarship programs

Tryfonidou leads the Horizon 2020 consortium (iPSpine; 2019–2023) bringing a transdisciplinary team of 21 partners together to address the challenges and bottlenecks of iPS-based advanced therapies towards their transition to the clinic. Here, chronic back pain due to intervertebral disc degeneration is employed as a show case. The project develops the iPS-technology and designed smart biomaterials to carry, protect and instruct the iPS cells within the degenerate disc environment. This work will be presented including ongoing activities focus on translating the developed methodology and tools towards clinically relevant animal models. The consortium optimized the protocol for the differentiated iPS-notochordal-like cells (iPS-NLCs) and shortlisted two biomaterials shortlisted based on their physicochemical, cytotoxicity, biomechanical and biocompatibility testing. Both were shown to be safe and have been tested with the progenitors of iPS-NLCs. An advanced platform (e.g., the dynamic loading bioreactor for disc tissue) was used to evaluate their performance: the biomaterials supported the iPS-NLC progenitors after injection into the degenerate disc and seem to also support their maturation towards NLCs. Furthermore, we confirmed the capacity of these cells to survive inside degenerated discs at 30 days upon injection in sheep, whereafter we continued with their evaluation at 3 months post-injection. We achieved full evaluation of the sheep spines, including biomechanical analysis using the portable spine biomechanics tester prior analysis at the macro- and microscopic, and biochemical level

Device-associated bacterial infections are a major and costly clinical challenge. This project aimed to develop a smart new biomaterial for implants that helps to protect against infection and inflammation, promote bone growth, and is biodegradable. Gallium (Ga) doped strontium-phosphate was coated on pure Magnesium (Mg) through a chemical conversion process. Mg was distributed in a graduated manner throughout the strontium-phosphate coating GaSrPO4, with a compact structure and a Ga-rich surface. We tested this sample for its biocompatibility, effects on bone remodeling and antibacterial activities including Staphylococcus aureus, S. epidermidis and E. coli - key strains causing infection and early failure of the surgical implantations in orthopaedics and trauma. Ga was distributed in a gradient way throughout the entire strontium-phosphate coating with a compact structure and a gallium-rich surface. The GaSrPO4 coating protected the underlying Mg from substantial degradation in minimal essential media at physiological conditions over 9 days. The liberated Ga ions from the coatings upon Mg specimens inhibited the growth of bacterial tested. The Ga dopants showed minimal interferences with the SrPO4 based coating, which boosted osteoblasts and undermined osteoclasts in in vitro co-cultures model. The results evidenced this new material may be further translated to preclinical trial in large animal model and towards clinical trial. Acknowledgements: Authors are grateful to the financial support from the Australian Research Council through the Linkage Scheme (ARC LP150100343). The authors acknowledge the facilities, and the scientific and technical assistance of the RMIT University and John Curtin School of Medical Research, Australian National University

Physiotherapy is a critical element in successful conservative management of low back pain (LBP). The aim of this study was to develop and evaluate a system with wearable inertial sensors to objectively detect sitting postures and performance of unsupervised exercises containing movement in multiple planes (flexion, extension, rotation). A set of 8 inertial sensors were placed on 19 healthy adult subjects. Data was acquired as they performed 7 McKenzie low-back exercises and 3 sitting posture positions. This data was used to train two models (Random Forest (RF) and XGBoost (XGB)) using engineered time series features. In addition, a convolutional neural network (CNN) was trained directly on the time series data. A feature importance analysis was performed to identify sensor locations and channels that contributed most to the models. Finally, a subset of sensor locations and channels was included in a hyperparameter grid search to identify the optimal sensor configuration and the best performing algorithm(s) for exercise classification. Models were evaluated using F1-score in a 10-fold cross validation approach. The optimal hardware configuration was identified as a 3-sensor setup using lower back, left thigh, and right ankle sensors with acceleration, gyroscope, and magnetometer channels. The XBG model achieved the highest exercise (F1=0.94±0.03) and posture (F1=0.90±0.11) classification scores. The CNN achieved similar results with the same sensor locations, using only the accelerometer and gyroscope channels for exercise classification (F1=0.94±0.02) and the accelerometer channel alone for posture classification (F1=0.91±0.03). This study demonstrates the potential of a 3-sensor lower body wearable solution (e.g. smart pants) that can identify proper sitting postures and exercises in multiple planes, suitable for low back pain. This technology has the potential to improve the effectiveness of LBP rehabilitation by facilitating quantitative feedback, early problem diagnosis, and possible remote monitoring

The use of implant biomaterials for prosthetic reconstructive surgery and osteosynthesis is consolidated in the orthopaedic field, improving the quality of life of patients and allowing for healthy and better ageing. However, there is the lack of advanced innovative methods to investigate the potentialities of smart biomaterials, particularly for the study of local effects of implant and osteointegration. Despite the complex process of osseointegration is difficult to recreate in vitro, the growing challenges in developing alternative models require to set-up and validate new approaches. Aim of the present study is to evaluate an advanced in vitro tissue culture model of osteointegration of titanium implants in human trabecular bone. Cubic samples (1.5×1.5 cm) of trabecular bone were harvested as waste material from hip arthroplasty surgery (CE AVEC 829/2019/Sper/IOR); cylindrical defects (2 mm Ø, 6 mm length) were created, and tissue specimens assigned to the following groups: 1) empty defects- CTR-; 2) defects implanted with a cytotoxic copper pin (Merck cod. 326429)- CTR+; 3) defects implanted with standard titanium pins of 6 µm-rough (ZARE S.r.l) -Ti6. Tissue specimens were cultured in mini rotating bioreactors in standard conditions, weekly assessing viability. At the 8-week-timepoint, immunoenzymatic, microtomographic, histological and histomorphometric analyses were performed. The model was able to simulate the effects of implantation of the materials, showing a drop in viability in CTR+, differently from Ti6 which appears to have a trophic effect on the bone. MicroCT and histological analysis supported the results, with lower BV/TV and Tb.Th values observed in CTR- compared to CTR+ and Ti6 and signs of matrix and bone deposition at the implant site. The collected data suggest the reliability of the tested model which can recreate the osseointegration process in vitro and can therefore be used for preliminary evaluations to reduce and refine in vivo preclinical models. Acknowledgment: This work was supported by Emilia-Romagna Region for the project “Sviluppo di modelli biologici in vitro ed in silico per la valutazione e predizione dell'osteointegrazione di dispositivi medici da impianto nel tessuto osseo”

Abstract. INTRODUCTION. In the NHS the structure of a “regular healthcare team” is no longer the case. The NHS is facing a workforce crisis where cross-covering of ward-based health professionals is at an all-time high, this includes nurses, doctors, therapists, pharmacists and clerks. Comprehensive post-operative care documentation is essential to maintain patient safety, reduce information clarification requests, delays in rehabilitation, treatment, and investigations. The value of complete surgical registry data is emerging, and in the UK this has recently become mandated, but the completeness of post-operative care documentation is not held to the same importance, and at present there is no published standard. This project summarises a 4-stage approach, including 6 audit cycles, >400 reviewed operation notes, over a 5 year period. OBJECTIVE. To deliver a sustainable change in post operative care documentation practices through quality improvement frameworks. METHODS. Stage 1: Characterise the problem and increase engagement through: SMART aims, process mapping, hybrid action-effect and driver diagram and stakeholder analysis. Multi disciplinary stakeholders were involved in achieving a consensus of evidence-based auditable criteria. Stage 2: Baseline audit to assess current practice. Stage 3: Intervention planning by stakeholders. Stage 4: Longitudinal monitoring through run charts and iterative refinement. RESULTS. Stage 1: Process mapping identified numerous downstream effects of the absence of critical information from operation notes, and the action-effect diagram highlighted the multiple unnecessary mitigating actions performed by ward staff. An MDT consensus was achieved on 15 essential criteria for complete documentation, including important negative fields. Interest-influence matrix identified stakeholder groups with high influence but low interest who needed engagement to deliver change. Stage 2: Baseline audit demonstrated unexpectedly poor documentation: >75% compliance in 4 criteria, and <50% compliance in 10 criteria, which elevated the interest of key stakeholders. Stage 3: A post-operative care template based on the 15 criteria was embedded within the existing IT software. It allowed use of existing operative templates, with a non-overwriting suffix requiring only two mouse clicks. Stage 4: Re-audit at 3 and 12 months showed improved and sustained compliance. At 24 months compliance had declined. Questionnaire of template usage identified problems of criteria response options, and lack of awareness of template by newly appointed staff. Template update improved compliance over the next 6 months (>75% compliance in 11 criteria). Finally, a further reaudit conducted 12 months after the template update (5 years post baseline audit) showed a sustained improvement in compliance (>75% compliance in 13 criteria). CONCLUSIONS. Simple innovation through quality improvement frameworks has changed documentation practices by 1) achieving a consensus from stakeholders, 2) a “shock and awe” moment to highlight existing poor documentation and increase engagement 3) implementing change which fit easily into existing systems, 4) respecting autonomy rather than enforcing change and 5) longitudinal monitoring using run charts and an iterative process to ensure the template remains fit for purpose. This model has now successfully been translated to other subspecialities within the orthopaedic department. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Nonunions occur in situations with interrupted fracture healing process and indicate conditions where the fracture has no potential to heal without further intervention. Per definition, no healing is detected nine months post operation and there is no visible progress of healing over the last three months. The classification of nonunions as hypertrophic, oligotrophic, atrophic and pseudoarthosis, as well as aseptic or septic, identifies mechanical and biological requirements for fracture healing that have not been met. The overall treatment strategy comprises identification and elimination of the problems. However, current clinical methods to determine the state of healing are based on highly subjective radiographic evaluation or clinical examination. A data collection telemetric system for objective continuous measurement of the load carried by a bridging smart implant was developed to assess the mechanical stability and monitor bone healing in complicated fracture situations. The first results from a clinical trial show that the system is capable to offer early warning of nonunions or poor fracture healing. Nonunions are often multifactorial in nature and not just related to a biomechanical problem. Their successful treatment requires consideration of both biological and mechanical aspects. Disturbed vascularity and stability are the most important factors. Infection could be another complicating factor resulting in unpredictable long-time treatment. New technologies for monitoring of fracture healing in addition to radiographic evaluation and clinical examination seem to be promising for early detection of nonunions

Foot pain and related problems are quite common in the community. It is reported that 24% of individuals older than 45 experienced foot pain. Also, it is stated that at least two thirds of individuals experiences moderate physical disability due to foot problems. In the absence of evaluation of risk factors such as limited ankle dorsiflexion in the early period of the diseases (Plantar fasciitis, Achilles Tendinopathy e.g.) and the lack of mobile systems with portable remote access, foot pain becomes refractory/chronic foot pain, secondary pathologies and ends with workload of 1., 2. and 3rd level healthcare services. In the literature, manuel and dijital methods have been used to analyze the ankle range of motion (ROM). These studies are generally based on placing protractors on the image and / or angle detection from inclination measurement by using the gyroscope sensor of the mobile device. Some of these applications are effective and they are designed to be suitable for measuring in a clinical setting by a physician or physiotherapist. To the best of our knowledge, there is no system developed to measure real-time ankle ROM remotely with collaboration of the patients. In this research, we proposed to develop an ankle ROM analyze system with smart phone application that can be used comfortably by subjects. We present a case of a 22-year-old male with a symptomatic pes planus. The mobile application, which was used for data collection, was designed and implemented for Android devices. Initially, before the mobile application home page is opened, a consent page was submitted to the acceptance of individual within the scope of Law (KVKK) data privacy. Then, the participant was asked to state his sociodemographic characteristics [age, gender, height, weight] and dominant side. No history of foot-ankle injury, trauma, and surgery was recorded. Activity pain of the foot was 6 according to visual anolog scale (VAS) in the mobile application. His ankle dorsiflexion was 15 ° by manuel goniometer. Besides, server was responsible for storing the collected data and ROM measurement. ROM was calculated by processing the foot video which was sent through the mobile application. During the processing phase, a segmentation model was used which was trained with image process and deep learning methods. With the developed system, we obtained the manual goniometric measurement result with 2 degrees deviation. As the application is calibrated, it is expected to approach the actual measurement of ROM. We can conclude that mobile app-goniometer result in dorsiflexion measurement is a novel promising evaluation method for ankle ROM. it will be easy and practical to detect and monitor risk factor of the diseases, decrease medical costs, provide health services in rural areas, and contribution to life quality and to reduce the workload on physicians and physiotherapist

Current Department of Health guidelines state that medical personnel should be ‘bare below the elbows’. Critics of this policy have raised concerns over the impact of these dress regulations on the portrayed image and professionalism of doctors. However, the importance of the doctor's appearance in relation to other professional attributes is largely unknown. The purpose of this study was to determine the opinion of patients and their relatives on the importance of appearance and the style of clothing worn by orthopaedic doctors. The secondary aim was to establish how patients would prefer orthopaedic doctors to be dressed. The study consisted of the administration of a survey questionnaire to 427 subjects attending the orthopaedic outpatient clinics in four hospitals across Scotland. Subjects were asked about the importance or otherwise of various aspects of the doctors’ appearance and responded using a modified Likert 5-point scale. Subjects’ rank preferences for four different styles of doctors’ clothing were also determined. The study was appropriately powered to identify a 0.5 difference in mean rank values with 0.90 power at a = 0.05. The majority of respondents felt doctors’ appearance was important but not as important as compassion, politeness and knowledge. Only 50% felt that the style of doctors clothing mattered; what proved more important was an impression of cleanliness and good personal hygiene. In terms of how patients would prefer doctors to dress in clinic, the most popular choice proved to be the smart casual style of dress, which conforms with the ‘bare below the elbows’ dress code policy. Indeed, the smart casual clothing style was the highest ranked choice irrespective of patient age, gender, regional or socioeconomic background

The successful application of smart implantable devices requires materials used to easily adapt and respond to their microenvironment via physical and chemical cues. Nanotopography, a known important factor in cellular processes (i.e. cellular adhesion, proliferation, and, differentiation), has become a central approach to imparting clinically relevant materials with bioactive and biomimetic properties. This work focuses on the use of Directed irradiation synthesis (DIS), to create nanostructures on dissimilar materials including surfaces of metals, semiconductors, and polymers. DIS is a novel method that allows for the tuning of both surface nanoscale topography and surface chemistry through the tailoring of ion beam parameters, including energy and fluence. The application of DIS to direct cellular interactions on Ti6Al4V, MgAZ31, and PEEK is presented. Topography and chemistry changes at the nanoscale were characterized by SEM, XPS, AFM, and Contact Angle. In vitro tests were performed using macrophages (JJ741A) and human aortic and bone marrow mesenchymal stem cell (MSCs). DIS promotes an advanced cell adhesion state where cells are orientated following the designed nanofeatures in all irradiated specimens. A delay on immune response due to low levels of TNFa and higher levels of IL10 on irradiated Ti6Al4V were observed. Modified PEEK showed 3-fold higher ALP content at 7 days compared to pristine samples, and porous MgAZ31 treated with DIS revealed lower corrosion state and increased cell proliferation of HBMMSCs. Controlling the nanopatterning in biomaterials using DIS enables the design of bioactive surfaces to highly promote implant integration and tissue regeneration

The selection of a proper material to be used as a scaffold or as a hydrogel to support, hold or encapsulate cells is both a critical and a difficult choice that will determine the success of failure of any tissue engineering and regenerative medicine (TERM) strategy. We believe that the use of natural origin polymers, including a wide range of marine origin materials, is the best option for many different approaches that allow for the regeneration of different tissues. In addition to the selection of appropriate material systems it is of outmost importance the development of processing methodologies that allow for the production of adequate scaffolds/matrices, in many cases incorporating bioactive/differentiation agents in their structures. An adequate cell source should be selected. In many cases efficient cell isolation, expansion and differentiation, and in many cases the selection of a specific sub-population, methodologies should be developed and optimized. We have been using different human cell sources namely: mesenchymal stem cells from bone marrow, mesenchymal stem cells from human adipose tissue, human cells from amniotic fluids and membranes and cells obtained from human umbilical cords. The development of dynamic ways to culture the cells and of distinct ways to stimulate their differentiation in 3D environments, as well as the use of nano-based systems to induce their differentiation and internalization into cells, is also a key part of some of the strategies that are being developed in our research group. The potential of each combination materials/cells, to be used to develop novel useful regeneration therapies will be discussed. The use of different cells and their interactions with different natural origin degradable scaffolds and smart hydrogels will be described. Several examples of TERM strategies to regenerate different types of musculoskeletal tissues will be presented. Relevance to orthopaedics will be highlighted

There are many factors which contribute to function after TKA. In this study we focus on the effect of varus-valgus (VV) balancing measured externally. A loose knee can show instability (Sharkey 2014) while too tight, flexion can be limited. Equal lateral-medial balancing at surgery leads to a better result (Unitt 2008; Gustke 2014), which is generally the surgical goal. Indeed similar varus and valgus laxity angles have been found in most studies in vitro (Markolf 2015; Boguszewski 2015) and in vivo (Schultz 2007; Clarke 2016; Heesterbeek 2008). The angular ranges have been 3–5 degrees at 10–15 Nm of knee moment, females having the higher angles. The goal of this study was to measure the varus and valgus laxity, as well as the functional outcome scores, of two cohorts; well-functioning total knees after at least one year follow-up, and subjects with healthy knees in a similar age group to the TKR's. Our hypothesis was that the results will be equal in the two groups. 50 normal subjects average age 66 (27 male, 23 female) and 50 TKA at 1 year follow-up minimum average age 68 years (16 male, 34 female) were recruited in this IRB study. The TKA's were performed by one surgeon (PAM) of one TKA design, balancing by gap equalization. Subjects completed a KSS evaluation form to determine functional, objective, and satisfaction scores. Varus and valgus measurements were made using the Smart Knee Fixture (Borukhov 2016) at 20 deg flexion with a moment of 10 Nm. The statistical results demonstrated that there was no significant difference in either varus or valgus laxity between the two groups (p= 0.9, 0.3 respectively). Pearson's correlation coefficient between varus and valgus laxity of the healthy group was 0.42, while for the TKA group was 0.55. In both cohorts varus laxity was significant higher than valgus laxity (p= 0.001. e. −5. for healthy subjects and p=0.0001 for TKA). The healthy group had higher functional and objective KSS scores (p= 0.005. e. −4. , and p=0.004. e. −5. respectively), but the same satisfaction scores as the TKA (p=0.3). No correlation was found between the total laxity of the TKA group and the KSS scores (functional, objective and satisfaction). Total laxity in females was significantly higher than in males in the healthy group, but no differences was found in the TKA group. The hypothesis of equal varus and valgus angles in the 2 groups was supported. The larger varus angle implied a less stiff lateral collateral compared with the medial collateral. If the TKA's were balanced equally at surgery, it is possible there was ligament remodeling over time. However the functional scores were inferior for the TKA compared with normal. This finding has not been highlighted in the literature so far. The causes could include weak musculature (Yoshida 2013), non-physiologic kinematics due to the TKA design, or the use of rigid materials in the TKA. The result presents a challenge to improve outcomes after TKA

The gelatin-based haemostyptic compound Spongostan was tested as a three-dimensional (3D) chondrocyte matrix in an in vitro model for autologous chondrocyte transplantation using cells harvested from bovine knees. In a control experiment of monolayer cultures, the proliferation or de-differentiation of bovine chondrocytes was either not or only marginally influenced by the presence of Spongostan (0.3 mg/ml).

In monolayers and 3-D Minusheet culture chambers, the cartilage-specific differentiation markers aggrecan and type-II collagen were ubiquitously present in a cell-associated fashion and in the pericellular matrix. The Minusheet cultures usually showed a markedly higher mRNA expression than monolayer cultures irrespective of whether Spongostan had been present or not during culture. Although the de-differentiation marker type-I collagen was also present, the ratio of type-I to type-II collagen or aggrecan to type-I collagen remained higher in Minusheet 3-D cultures than in monolayer cultures irrespective of whether Spongostan had been included in or excluded from the monolayer cultures. The concentration of GAG in Minusheet cultures reached its maximum after 14 days with a mean of 0.83 ± 0.8 μg/10⁶ cells; mean ±, sem, but remained considerably lower than in monolayer cultures with/without Spongostan.

Our results suggest that Spongostan is in principle suitable as a 3-D chondrocyte matrix, as demonstrated in Minusheet chambers, in particular for a culture period of 14 days. Clinically, differentiating effects on chondrocytes, simple handling and optimal formability may render Spongostan an attractive 3-D scaffold for autologous chondrocyte transplantation.