Treatment of calvarial defects by resorbable and non-resorbable sonic activated polymer pins and mouldable titanium mesh in two dogs: a case report.

BACKGROUND: To date, calvarial defects in dogs have traditionally been addressed with different types of implants including bone allograft, polymethylmethacrylate and titanium mesh secured with conventional metallic fixation methods. This report describes the use of an absorbable and non absorbable novel polymer fixation method, Bonewelding® technology, in combination with titanium mesh for the repair of calvarial defects in two dogs. The clinical outcomes and comparative complication using resorbable and non-resorbable thermoplastic pins were compared. CASE PRESENTATION: This report of two cases documents the repair of a traumatic calvarial fracture in an adult male Greyhound and a cranioplasty following frontal bone tumor resection in an adult female Cavalier King Charles Spaniel with the use of a commercially available titanium mesh secured with an innovative thermoplastic polymer screw system (Bonewelding®). The treatment combination aimed to restore cranial structure, sinus integrity and cosmetic appearance. A mouldable titanium mesh was cut to fit the bone defect of the frontal bone and secured with either resorbable or non-resorbable polymer pins using Bonewelding® technology. Gentamycin-impregnated collagen sponge was used intraoperatively to assist with sealing of the frontal sinuses. Calvarial fracture and post-operative implant positioning were advised using computed tomography. A satisfactory restoration of skull integrity and cosmetic result was achieved, and long term clinical outcome was deemed clinically adequate with good patient quality of life. Postoperative complications including rostral mesh uplift with minor associated clinical signs were encountered when resorbable pins were used. No postoperative complications were experienced in non-resorbable pins at 7 months follow-up, by contrast mesh uplift was noted 3 weeks post-procedure in the case treated using absorbable pins. CONCLUSIONS: The report demonstrates the innovative use of sonic-activated polymer pins (Bonewelding® technology) alongside titanium mesh is a suitable alternative technique for skull defect repair in dogs. The use of Bonewelding® may offer advantages in reduction of surgical time. Further, ultrasonic pin application may be less invasive than alternative metallic fixation and potentially reduces bone trauma. Polymer systems may offer enhanced mesh-bone integration when compared to traditional metallic implants. The use of polymer pins demonstrates initial potential as a fixation method in cranioplasty. Initial findings in a single case comparison indicate a possible advantage in the use of non-absorbable over the absorbable systems to circumvent complications associated with variable polymer degradation, further long term studies with higher patient numbers are required before reliable conclusions can be made.

Characterization of New PEEK/HA Composites with 3D HA Network Fabricated by Extrusion Freeforming.

Addition of bioactive materials such as calcium phosphates or Bioglass, and incorporation of porosity into polyetheretherketone (PEEK) has been identified as an effective approach to improve bone-implant interfaces and osseointegration of PEEK-based devices. In this paper, a novel production technique based on the extrusion freeforming method is proposed that yields a bioactive PEEK/hydroxyapatite (PEEK/HA) composite with a unique configuration in which the bioactive phase (i.e., HA) distribution is computer-controlled within a PEEK matrix. The 100% interconnectivity of the HA network in the biocomposite confers an advantage over alternative forms of other microstructural configurations. Moreover, the technique can be employed to produce porous PEEK structures with controlled pore size and distribution, facilitating greater cellular infiltration and biological integration of PEEK composites within patient tissue. The results of unconfined, uniaxial compressive tests on these new PEEK/HA biocomposites with 40% HA under both static and cyclic mode were promising, showing the composites possess yield and compressive strength within the range of human cortical bone suitable for load bearing applications. In addition, preliminary evidence supporting initial biological safety of the new technique developed is demonstrated in this paper. Sufficient cell attachment, sustained viability in contact with the sample over a seven-day period, evidence of cell bridging and matrix deposition all confirmed excellent biocompatibility.

Extending the Family of V(4+) S=(1/2) Kagome Antiferromagnets.

The ionothermal synthesis, structure, and magnetic susceptibility of a novel inorganic-organic hybrid material, imidazolium vanadium(III,IV) oxyfluoride [C3 H5 N2 ][V9 O6 F24 (H2 O)2 ] (ImVOF) are presented. The structure consists of inorganic vanadium oxyfluoride slabs with kagome layers of V(4+) S=${{ 1/2 }}$ ions separated by a mixed valence layer. These inorganic slabs are intercalated with imidazolium cations. Quinuclidinium (Q) and pyrazinium (Pyz) cations can also be incorporated into the hybrid structure type to give QVOF and PyzVOF analogues, respectively. The highly frustrated topology of the inorganic slabs, along with the quantum nature of the magnetism associated with V(4+) , means that these materials are excellent candidates to host exotic magnetic ground states, such as the highly sought quantum spin liquid. Magnetic susceptibility measurements of all samples suggest an absence of conventional long-range magnetic order down to 2 K despite considerable antiferromagnetic exchange.

Describing and Comparing Patient Factors Associated with Use of Parenteral Iron before and after Implementation of an Order Set for Parenteral Iron (DECODE IRON).

Background: In select clinical scenarios, IV administration of iron is suitable for management of iron deficiency anemia; however, for most patients, oral administration of iron is the mainstay of treatment. At the Red Deer Regional Hospital Centre, in Red Deer, Alberta, high utilization of IV iron has resulted in limited access to this medication for the treatment of ambulatory patients, as well as significant usage of health care resources. Objectives: The primary objective was to compare patient characteristics, specifically pretreatment laboratory test results and previous use of oral iron, among those receiving IV iron therapy in an ambulatory setting before and after implementation of an iron sucrose order set. For secondary objectives, the aforementioned groups were compared with regard to meeting the diagnostic criteria for iron deficiency anemia, with or without pretreatment oral iron or blood transfusion, and the dosing characteristics for IV iron. Methods: A retrospective electronic chart review was performed for ambulatory patients who received IV iron between January 1, 2020, and January 31, 2022. Results: A total of 436 unique treatment courses were included in the analysis. The following pretreatment laboratory results were observed before and after implementation of the iron sucrose order set: mean hemoglobin 105.8 (standard deviation [SD] 21.9) g/L versus 102.2 (SD 18.5) g/L; mean of mean corpuscular volume (MCV) 82.2 (SD 9.4) fL versus 79.2 (SD 8.9) fL; and median ferritin 7 (interquartile range [IQR] 4-12) µg/L versus 6 (IQR 4-11) µg/L. Only the difference in MCV values was statistically significant (p = 0.001). Conclusions: The implementation of an iron sucrose order set for ambulatory patients did not have a significant effect on pretreatment laboratory parameters among patients for whom IV iron was prescribed. Further stewardship initiatives could be beneficial in improving the appropriateness of IV iron use.

Contexte: Dans certains scénarios cliniques, l'administration de fer par voie intraveineuse (IV) convient à la prise en charge de l'anémie ferriprive; cependant, pour la plupart des patients, l'administration de fer par voie orale constitue le pilier du traitement. Au centre hospitalier régional Red Deer, à Red Deer, en Alberta, l'utilisation élevée du fer par IV a entraîné un accès limité à ce médicament pour le traitement des patients ambulatoires, ainsi qu'une utilisation importante des ressources de santé. Objectifs: L'objectif principal consistait à comparer les caractéristiques des patients, en particulier les résultats de tests de laboratoire avant traitement et l'utilisation antérieure de fer par voie orale, chez ceux recevant un traitement de fer par IV en milieu ambulatoire avant et après la mise en oeuvre d'un protocole de prescription de fer sucrosé. Les objectifs secondaires, quant à eux, étaient la comparaison des groupes susmentionnés en ce qui concerne la satisfaction des critères diagnostiques de l'anémie ferriprive, avec ou sans prétraitement de fer administré par voie orale ou par transfusion sanguine, ainsi que les caractéristiques posologiques du fer administré par IV. Méthodes: Un examen rétrospectif des dossiers électroniques a été réalisé pour les patients ambulatoires ayant reçu du fer par IV entre le 1er janvier 2020 et le 31 janvier 2022. Résultats: Au total, 436 traitements uniques ont été inclus dans l'analyse. Les résultats suivants de tests de laboratoire avant traitement ont été observés avant et après la mise en oeuvre du protocole de prescription de fer sucrosé: hémoglobine moyenne 105,8 g/L (écart type [ÉT] 21,9) contre 102,2 g/L (ÉT 18,5); moyenne du volume corpusculaire moyen (VCM) 82,2 fL (ÉT 9,4) contre 79,2 fL (ÉT 8,9); et ferritine médiane 7 µg/L (intervalle interquartile [IIQ] 4­12) contre 6 µg/L (IQR 4­11). La seule différence statistiquement significative concernait les valeurs VCM (p = 0,001). Conclusions: La mise en oeuvre d'un protocole de prescription de fer sucrosé pour les patients ambulatoires n'a pas eu d'effet significatif sur les paramètres biologiques avant traitement chez les patients pour lesquels du fer par IV a été prescrit. D'autres initiatives de gestion pourraient être bénéfiques pour améliorer la pertinence de l'utilisation du fer IV.

Validity and reliability of the session-RPE method for quantifying training in Australian football: a comparison of the CR10 and CR100 scales.

The purpose of this study was to examine and compare the criterion validity and test-retest reliability of the CR10 and CR100 rating of perceived exertion (RPE) scales for team sport athletes that undertake high-intensity, intermittent exercise. Twenty-one male Australian football (AF) players (age: 19.0 ± 1.8 years, body mass: 83.92 ± 7.88 kg) participated the first part (part A) of this study, which examined the construct validity of the session-RPE (sRPE) method for quantifying training load in AF. Ten male athletes (age: 16.1 ± 0.5 years) participated in the second part of the study (part B), which compared the test-retest reliability of the CR10 and CR100 RPE scales. In part A, the validity of the sRPE method was assessed by examining the relationships between sRPE, and objective measures of internal (i.e., heart rate) and external training load (i.e., distance traveled), collected from AF training sessions. Part B of the study assessed the reliability of sRPE through examining the test-retest reliability of sRPE during 3 different intensities of controlled intermittent running (10, 11.5, and 13 km·h(-1)). Results from part A demonstrated strong correlations for CR10- and CR100-derived sRPE with measures of internal training load (Banisters TRIMP and Edwards TRIMP) (CR10: r = 0.83 and 0.83, and CR100: r = 0.80 and 0.81, p < 0.05). Correlations between sRPE and external training load (distance, higher speed running and player load) for both the CR10 (r = 0.81, 0.71, and 0.83) and CR100 (r = 0.78, 0.69, and 0.80) were significant (p < 0.05). Results from part B demonstrated poor reliability for both the CR10 (31.9% CV) and CR100 (38.6% CV) RPE scales after short bouts of intermittent running. Collectively, these results suggest both CR10- and CR100-derived sRPE methods have good construct validity for assessing training load in AF. The poor levels of reliability revealed under field testing indicate that the sRPE method may not be sensible to detecting small changes in exercise intensity during brief intermittent running bouts. Despite this limitation, the sRPE remains a valid method to quantify training loads in high-intensity, intermittent team sport.

Consensus on occupational health competencies for UK first contact physiotherapists.

BACKGROUND: Patients at risk of preventable sickness absence frequently attend at primary care. First contact physiotherapists (FCP) may provide an optimal way of reducing this risk; however, there is significant variability in clinical practice, limited research directing best practice and this work and health role is traditionally seen as outside of the 'therapeutic relationship'. If FCP's training and development in this area is considered, FCP's will be able to effectively conduct fitness for work and sickness absence certification within UK primary care settings. AIMS: This study aimed to reach expert consensus for work-related competencies for FCP practice for patients at risk of preventable sickness absence. METHODS: A modified Delphi technique involved a UK-wide FCP expert panel completing three rounds of an online questionnaire. The initial 30-competency questionnaire, based on two separate Nominal Group Techniques in a FCP and Association of Chartered Physiotherapists in Occupational Health and Ergonomics (ACPOHE) physiotherapist cohort and Health Education England's published Roadmap to Practice, covered occupational health specific items (knowledge and skills) related to the topic. Consensus threshold was set a priori at 70% level of group agreement. Items not reaching consensus were modified and new items added based on themes from qualitative data from the open-ended free text questions present in each section. Items that reached values greater than or equal to 70% of agreement among experts were considered definitive for the competency items. Items between 51% and 69% of agreement were included for the next round and those items with less than or equal to 50% of agreement were considered unnecessary and were excluded. In the third round, the occupational health (OH) specific contents for primary care were classified according to the degree of consensus as follows: strong (≥70% of agreement), moderate (51-69% of agreement) and weak (50% of agreement) based on the maximum consensus reached. RESULTS: Of the 30 initial competencies, 20 (67%) reached a strong degree of consensus and 2 (7%) reached a moderate degree of consensus and 8 (27%) competencies were not recommended (≤50% of agreement). 20 OH specific competencies reached a priori consensus level of agreement to provide the final group list. CONCLUSIONS: This paper provides an empirically derived list of OH competencies for FCP education in primary care 'first point of care' physiotherapy with a high level of expert agreement and high retention rate between rounds. CONTRIBUTION OF THE PAPER.

A cross-sectional investigation of back pain beliefs and fear in physiotherapy and sport undergraduate students.

BACKGROUND: Although low back pain (LBP) beliefs have been well investigated in mainstream healthcare discipline students, the beliefs within sports-related study students, such as Sport and Exercise Science (SES), Sports Therapy (ST), and Sport Performance and Coaching (SPC) programmes have yet to be explored. This study aims to understand any differences in the beliefs and fear associated with movement in students enrolled in four undergraduate study programmes-physiotherapy (PT), ST, SES, and SPC. METHOD: 136 undergraduate students completed an online survey. All participants completed the Tampa Scale of Kinesiophobia (TSK) and Back Beliefs Questionnaire (BBQ). Two sets of two-way between-subjects Analysis of Variance (ANOVA) were conducted for each outcome of TSK and BBQ, with the independent variables of the study programme, study year (1st, 2nd, 3rd), and their interaction. RESULTS: There was a significant interaction between study programme and year for TSK (F(6, 124) = 4.90, P < 0.001) and BBQ (F(6, 124) = 8.18, P < 0.001). Post-hoc analysis revealed that both PT and ST students had lower TSK and higher BBQ scores than SES and SPC students particularly in the 3rd year. CONCLUSIONS: The beliefs of clinicians and trainers managing LBP are known to transfer to patients, and more negative beliefs have been associated with greater disability. This is the first study to understand the beliefs about back pain in various sports study programmes, which is timely, given that the management of injured athletes typically involves a multidisciplinary team.

Principles of empiric antimicrobial usage and dosing: Lessons learned.

A lack of clinical response to empiric antimicrobials behooves the clinician to reflect further on diagnostic considerations. When prescribing antibiotics, determining the correct dose, most optimal route of administration, and considering the pharmacokinetic properties of the drug with respect to clinical and patient factors are crucial.

Primary care first contact practitioner's (FCP) challenges and learning and development needs in providing fitness for work and sickness absence certification: consensus development.

BACKGROUND: As yet, the benefit of the Fit Note has not been convincingly demonstrated, although a limited body of research suggests that provision of fitness for work advice and sickness absence certification may be improved with training and case-specific direction. The role of certifying sickness absence in the UK has traditionally been conducted by General Practitioners, but this role has now been extended to First Contact Practitioner (FCP) Physiotherapists in primary care. Therefore, FCPs may offer an ideal solution to the current challenges faced within primary care for those with a musculoskeletal (MSK) condition at risk of sickness absence from their work environment. OBJECTIVES: The main aim of this study was to identify the challenges and key learning and development needs of FCPs in response to providing Occupational Health (OH) information in the form of fitness for work advice and sickness certification for patients with MSK conditions within primary care. DESIGN: Consensus was generated using an online modified version of the Nominal Group Technique (NGT) method. A priori consensus threshold of 60% was used in the voting stage. PARTICIPANTS: NGT participants included clinicians with experience in managing MSK conditions in primary care within the FCP model of care. All participants generated, voted, and ranked the items using an online platform. CONCLUSIONS: This research adds new evidence regarding the challenges and learning and development needs identified by a group of FCPs working within primary care in consideration of sickness absence certification and fitness for work advice. The items highlighted provide evidence to complement Health Education England's FCP A Roadmap to Practice educational pathway and informs on professional development needs in this area.

Nonlinear micro finite element models based on digital volume correlation measurements predict early microdamage in newly formed bone.

Bone regeneration in critical-sized defects is a clinical challenge, with biomaterials under constant development aiming at enhancing the natural bone healing process. The delivery of bone morphogenetic proteins (BMPs) in appropriate carriers represents a promising strategy for bone defect treatment but optimisation of the spatial-temporal release is still needed for the regeneration of bone with biological, structural, and mechanical properties comparable to the native tissue. Nonlinear micro finite element (µFE) models can address some of these challenges by providing a tool able to predict the biomechanical strength and microdamage onset in newly formed bone when subjected to physiological or supraphysiological loads. Yet, these models need to be validated against experimental data. In this study, experimental local displacements in newly formed bone induced by osteoinductive biomaterials subjected to in situ X-ray computed tomography compression in the apparent elastic regime and measured using digital volume correlation (DVC) were used to validate µFE models. Displacement predictions from homogeneous linear µFE models were highly correlated to DVC-measured local displacements, while tissue heterogeneity capturing mineralisation differences showed negligible effects. Nonlinear µFE models improved the correlation and showed that tissue microdamage occurs at low apparent strains. Microdamage seemed to occur next to large cavities or in biomaterial-induced thin trabeculae, independent of the mineralisation. While localisation of plastic strain accumulation was similar, the amount of damage accumulated in these locations was slightly higher when including material heterogeneity. These results demonstrate the ability of the nonlinear µFE model to capture local microdamage in newly formed bone tissue and can be exploited to improve the current understanding of healing bone and mechanical competence. This will ultimately aid the development of BMPs delivery systems for bone defect treatment able to regenerate bone with optimal biological, mechanical, and structural properties.

Comparison of bone formation mediated by bone morphogenetic protein delivered by nanoclay gels with clinical techniques (autograft and InductOs®) in an ovine bone model.

Development of a growth factor delivery vehicle providing appropriate temporal-spatial release together with an appropriate preclinical large animal model to evaluate bone formation is critical in the development of delivery strategies for bone tissue regeneration. Smectite nanoclays such as LAPONITE™ possess unique thixotropic and protein retention properties offering promise for use in growth factor delivery in bone repair and regeneration. This study has examined bone formation mediated by a clinically approved growth factor delivery system (InductOs®) in combination with Laponite gel in an aged female ovine femoral condyle defect preclinical model (10 weeks). Two different designs, one containing a low volume of Laponite gel (LLG) in combination with the InductOs® absorbable collagen sponge (ACS), the other in which Laponite gel formed the implant (HLG), were compared against InductOs® alone and an autograft positive control. Thus, five groups: (i) empty defect, (ii) autograft, (iii) BMP2 + ACS, (iv) BMP2 + ACS + LLG and (v) BMP2 + HLG + ACS were examined in 9 mm × 12 mm defects performed bilaterally in the medial femoral condyles of 24 aged (>5 years) sheep. Bone formation within the defect was assessed using micro-computed tomography (micro-CT), digital volume correlation (DVC) for biomechanical characterisation as well as histology. The autograft and InductOs® mediated enhanced bone formation (p < 0001) compared to blank controls, while no significant differences were observed between the Laponite/Collagen/BMP delivery vehicles. However, the current study illustrated the excellent biocompatibility of Laponite and its ability to deliver localised active BMP-2, with the opportunity for improved efficacy with further optimisation. Interestingly, DVC-computed strain distributions indicated that the regenerated bone structure is mechanically adapted to bear external loads from the early remodelling stages of the bone reparation cascade. The current studies of selected nanoclay delivery platforms for BMP, assessed in a clinically relevant large animal model auger well for the development of bone fracture therapeutics for an ageing population.

In vitro and in vivo investigation of a zonal microstructured scaffold for osteochondral defect repair.

Articular cartilage is comprised of zones that vary in architecture, extracellular matrix composition, and mechanical properties. Here, we designed and engineered a porous zonal microstructured scaffold from a single biocompatible polymer (poly [ϵ-caprolactone]) using multiple fabrication strategies: electrospinning, spherical porogen leaching, directional freezing, and melt electrowriting. With this approach we mimicked the zonal structure of articular cartilage and produced a stiffness gradient through the scaffold which aligns with the mechanics of the native tissue. Chondrocyte-seeded scaffolds accumulated extracellular matrix including glycosaminoglycans and collagen II over four weeks in vitro. This prompted us to further study the repair efficacy in a skeletally mature porcine model. Two osteochondral lesions were produced in the trochlear groove of 12 animals and repaired using four treatment conditions: (1) microstructured scaffold, (2) chondrocyte seeded microstructured scaffold, (3) MaioRegen™, and (4) empty defect. After 6 months the defect sites were harvested and analyzed using histology, micro computed tomography, and Raman microspectroscopy mapping. Overall, the scaffolds were retained in the defect space, repair quality was repeatable, and there was clear evidence of osteointegration. The repair quality of the microstructured scaffolds was not superior to the control based on histological scoring; however, the lower score was biased by the lack of histological staining due to the limited degradation of the implant at 6 months. Longer follow up studies (e.g., 1 yr) will be required to fully evaluate the efficacy of the microstructured scaffold. In conclusion, we found consistent scaffold retention, osteointegration, and prolonged degradation of the microstructured scaffold, which we propose may have beneficial effects for the long-term repair of osteochondral defects.

Bicyclic heteroaryl inhibitors of stearoyl-CoA desaturase: from systemic to liver-targeting inhibitors.

Optimization of a lead thiazole amide MF-152 led to the identification of potent bicyclic heteroaryl SCD1 inhibitors with good mouse pharmacokinetic profiles. In a view to target the liver for efficacy and to avoid SCD1 inhibition in the skin and eyes where adverse effects were previously observed in rodents, representative systemically-distributed SCD1 inhibitors were converted into liver-targeting SCD1 inhibitors.

Clinical outcomes following intra-articular injection of autologous adipose-derived mesenchymal stem cells for the treatment of osteoarthritis in dogs characterized by weight-bearing asymmetry.

AIMS: This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients. METHODS: With informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05. RESULTS: AdMSCs demonstrated stem cell-like characteristics. LOAD scores were significantly lower at week 4 compared with preinjection (p = 0.021). The mCOAST improved significantly after three months (p = 0.001) and six months (p = 0.001). Asymmmetry indices decreased from four weeks post-injection and remained significantly lower at six months (p = 0.025). CONCLUSION: These improvements in quality of life, reduction in pain on examination, and improved symmetry in dogs injected with AdMSCs and PRP support the effectiveness of this combined treatment for symptom modification in canine OA for six months. Cite this article: Bone Joint Res 2021;10(10):650-658.

Short-Term Evaluation of Cellular Fate in an Ovine Bone Formation Model.

The ovine critical-sized defect model provides a robust preclinical model for testing tissue-engineered constructs for use in the treatment of non-union bone fractures and severe trauma. A critical question in cell-based therapies is understanding the optimal therapeutic cell dose. Key to defining the dose and ensuring successful outcomes is understanding the fate of implanted cells, e.g., viability, bio-distribution and exogenous infiltration post-implantation. This study evaluates such parameters in an ovine critical-sized defect model 2 and 7 days post-implantation. The fate of cell dose and behaviour post-implantation when combined with nanomedicine approaches for multi-model tracking and remote control using external magnetic fields is also addressed. Autologous STRO-4 selected mesenchymal stromal cells (MSCs) were labelled with a fluorescent lipophilic dye (CM-Dil), functionalised magnetic nanoparticles (MNPs) and delivered to the site within a naturally derived bone extracellular matrix (ECM) gel. Encapsulated cells were implanted within a critical-sized defect in an ovine medial femoral condyle and exposed to dynamic gradients of external magnetic fields for 1 h per day. Sheep were sacrificed at 2 and 7 days post-initial surgery where ECM was harvested. STRO-4-positive (STRO-4+) stromal cells expressed osteocalcin and survived within the harvested gels at day 2 and day 7 with a 50% loss at day 2 and a further 45% loss at 7 days. CD45-positive leucocytes were also observed in addition to endogenous stromal cells. No elevation in serum C-reactive protein (CRP) or non-haem iron levels was observed following implantation in groups containing MNPs with or without magnetic field gradients. The current study demonstrates how numbers of therapeutic cells reduce substantially after implantation in the repair site. Cell death is accompanied by enhanced leucocyte invasion, but not by inflammatory blood marker levels. Crucially, a proportion of implanted STRO-4+ stromal cells expressed osteocalcin, which is indicative of osteogenic differentiation. Furthermore, MNP labelling did not alter cell number or result in a further deleterious impact on stromal cells following implantation.

SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors.

Elevated stearoyl-CoA desaturase (SCD) activity has been linked to a number of metabolic disorders including obesity and type II diabetes. Compound 3j, a potent SCD inhibitor (human HepG2 IC(50)=1nM) was identified from the optimization of a lead thiazole compound MF-152 with over 100-fold improvement in potency. In a 4-week chronic oral dosing at 0.2mg/kg, 3j gave a robust 24% prevention of body weight gain in mice fed on a high fat diet accompanied with an improved metabolic profile on insulin and glucose levels.

Guidelines for the Execution of True Spherical Osteotomies Using a Modified Dome Blade Design.

OBJECTIVES: The purpose of this study was to explore the trigonometric principles of the spherical osteotomy, establish guidelines for its application and test the guidelines on bone models using a new blade design. We propose a new rule of osteotomies incorporating the outlined geometric principles, and applicable to the use of spherical cuts in veterinary orthopaedic surgery. MATERIALS AND METHODS: The trigonometric principles for the execution of neutral, closing and opening spherical osteotomies were explored in silico. A modification of the existing commercially available dome blade was designed and manufactured such that it facilitated the performance of spherical osteotomy with a minimized blade radius. A pilot study was performed whereby the modified dome blade was used to create spherical osteotomy in canine radial bone models. The surfaces of the osteotomy models were laser-scanned using a three-dimensional (3D) scanner; the resultant scans were imported into and analysed using a commercial 3D analysis software. The accuracy of osteotomy execution was measured as the distance between the targeted centre of osteotomy and the actual centre of osteotomy as found on the 3D scans. RESULTS: By utilizing the geometric principles of spherical osteotomy, an accurate osteotomy position was achieved. The centre of the spherical cut performed on bone models was confirmed to be within 5% tolerance of the location as planned in silico demonstrating the accurate and relevant clinical application of geometric principles. CLINICAL SIGNIFICANCE: The trigonometric guidelines for the execution of spherical osteotomy can be applied in a pre-clinical environment with accuracy. The new guidelines combined with the proposed new rule for spherical osteotomy utilizing the new blade design are translatable into clinical application, permitting the surgeon to accurately plan osteotomy application while mitigating the significant loss of bone-to-bone contact during correction of torsional deformities inherent in the principles of dome osteotomy use.

Treatment of a large osseous defect in a feline tarsus using a stem cell-seeded custom implant.

The aim of this study is to describe the treatment of an infected segmental bone defect in a cat using a novel, custom-designed titanium implant seeded with adipose-derived stem cells (AdMSCs) to facilitate osseous ingrowth and preserve limb function. Large bone defects occur secondary to trauma, infection, or neoplasia and often result in amputation. We established a novel autologous AdMSC-impregnated trabecular metal spacer made using 3D printing, to bridge the distal tibia and metatarsal bones in the left pelvic limb of a cat that had previously undergone right pelvic limb amputation. Six months postoperatively, there was radiographic evidence of bone growth and implant integration. A titanium spacer seeded with AdMSCs successfully encouraged bone ingrowth in a large defect site and successfully preserved limb function. However, further studies are needed to justify the use of differentiated stem cell impregnated mesh as a framework to bridge large bone defects.

Exploratory Full-Field Strain Analysis of Regenerated Bone Tissue from Osteoinductive Biomaterials.

Biomaterials for bone regeneration are constantly under development, and their application in critical-sized defects represents a promising alternative to bone grafting techniques. However, the ability of all these materials to produce bone mechanically comparable with the native tissue remains unclear. This study aims to explore the full-field strain evolution in newly formed bone tissue produced in vivo by different osteoinductive strategies, including delivery systems for BMP-2 release. In situ high-resolution X-ray micro-computed tomography (microCT) and digital volume correlation (DVC) were used to qualitatively assess the micromechanics of regenerated bone tissue. Local strain in the tissue was evaluated in relation to the different bone morphometry and mineralization for specimens (n = 2 p/treatment) retrieved at a single time point (10 weeks in vivo). Results indicated a variety of load-transfer ability for the different treatments, highlighting the mechanical adaptation of bone structure in the early stages of bone healing. Although exploratory due to the limited sample size, the findings and analysis reported herein suggest how the combination of microCT and DVC can provide enhanced understanding of the micromechanics of newly formed bone produced in vivo, with the potential to inform further development of novel bone regeneration approaches.

Nanopatterned Titanium Implants Accelerate Bone Formation In Vivo.

Accelerated de novo formation of bone is a highly desirable aim of implants targeting musculoskeletal injuries. To date, this has primarily been addressed by biologic factors. However, there is an unmet need for robust, highly reproducible yet economic alternative strategies that strongly induce an osteogenic cell response. Here, we present a surface engineering method of translating bioactive nanopatterns from polymeric in vitro studies to clinically relevant material for orthopedics: three-dimensional, large area metal. We use a titanium-based sol-gel whereby metal implants can be engineered to induce osteoinduction both in vitro and in vivo. We show that controlled disordered nanotopographies presented as pillars with 15-25 nm height and 100 nm diameter on titanium dioxide effectively induce osteogenesis when seeded with STRO-1-enriched human skeletal stem cells in vivo subcutaneous implantation in mice. After 28 days, samples were retrieved, which showed a 20-fold increase in osteogenic gene induction of nanopatterned substrates, indicating that the sol-gel nanopatterning method offers a promising route for translation to future clinical orthopedic implants.