Manufacturing conditioned roughness and wear of biomedical oxide ceramics for all-ceramic knee implants

Background: Ceramic materials are used in a growing proportion of hip joint prostheses due to their wear resistance and biocompatibility properties. However, ceramics have not been applied successfully in total knee joint endoprostheses to date. One reason for this is that with strict surface quality requirements, there are significant challenges with regard to machining. High-toughness bioceramics can only be machined by grinding and polishing processes. The aim of this study was to develop an automated process chain for the manufacturing of an all-ceramic knee implant. Methods: A five-axis machining process was developed for all-ceramic implant components. These components were used in an investigation of the influence of surface conformity on wear behavior under simplified knee joint motion. Results: The implant components showed considerably reduced wear compared to conventional material combinations. Contact area resulting from a variety of component surface shapes, with a variety of levels of surface conformity, greatly influenced wear rate. Conclusions: It is possible to realize an all-ceramic knee endoprosthesis device, with a precise and affordable manufacturing process. The shape accuracy of the component surfaces, as specified by the design and achieved during the manufacturing process, has a substantial influence on the wear behavior of the prosthesis. This result, if corroborated by results with a greater sample size, is likely to influence the design parameters of such devices.

Suivi de la contamination métallique et organique de deux lots de moules (Mytilus edulis) implantés au port de Goury et à l'Anse des Moulinets (Manche) - Année 2015

Dans le cadre de la surveillance des rejets non actifs de l’usine AREVA NC, les concentrations de différents éléments et substances chimiques sont suivies dans des moules (Mytilus Edulis) sur les points Goury et Moulinets. Ce rapport présente les résultats pour l’année 2015. Les variations saisonnières sont présentées pour chaque paramètre surveillé. Les teneurs mesurées sont comparées aux données nationales et régionales du Réseau d’Observation de la contamination chimique (ROCCH).

In situ epicatechin-loaded hydrogel implants for local drug delivery to spinal column for effective management of post-traumatic spinal injuries

Purpose: To prepare hydrogels loaded with epicatechin, a strong antioxidant, anti-inflammatory, and neuroprotective tea flavonoid, and characterise them in situ as a vehicle for prolonged and safer drug delivery in patients with post-traumatic spinal cord injury. Methods: Five in situ gel formulations were prepared using chitosan and evaluated in terms of their visual appearance, clarity, pH, viscosity, and in vitro drug release. In vivo anti-inflammatory activity was determined and compared with 2 % piroxicam gel as standard. Motor function activity in a rat model of spinal injury was examined comparatively with i.v. methylprednisolone as standard. Results: The N-methyl pyrrolidone solution (containing 1 % w/w epicatechin with 2 to 10 % w/w chitosan) of the in situ gel formulation had a uniform pH in the range of 4.01 ± 0.12 to 4.27 ± 0.02. High and uniform drug loading, ranging from 94.48 ± 1.28 to 98.08 ± 1.24 %, and good in vitro drug release (79.48 ± 2.84 to 96.48 ± 1.02 % after 7 days) were achieved. The in situ gel prepared from 1 % epicatechin and 2 % chitosan (E5) showed the greatest in vivo anti-inflammatory activity (60.58 % inhibition of paw oedema in standard carrageenan-induced hind rat paw oedema model, compared with 48.08 % for the standard). The gels showed significant therapeutic effectiveness against post-traumainduced spinal injury in rats. E5 elicited maximum motor activity (horizontal bar test) in the spinal injury rat model; the rats that received E5 treatment produced an activity score of 3.62 ± 0.02 at the end of 7 days, compared with 5.0 ± 0.20 following treatment with the standard. Conclusion: In situ epicatechin-loaded gel exhibits significant neuroprotective and anti-inflammatory effects, and therefore can potentially be used for prolonged and safe drug delivery in patients with traumatic spinal cord injury.

The impact of storage conditions upon gentamicin coated antimicrobial implants

A systematic approach was developed to investigate the stability of gentamicin sulfate (GS) and GS/poly (lactic-co-glycolic acid) (PLGA) coatings on hydroxyapatite surfaces. The influence of environmental factors (light, humidity, oxidation and heat) upon degradation of the drug in the coatings was investigated using liquid chromatography with evaporative light scattering detection and mass spectrometry. GS coated rods were found to be stable across the range of environments assessed, with only an oxidizing atmosphere resulting in significant changes to the gentamicin composition. In contrast, rods coated with GS/PLGA were more sensitive to storage conditions with compositional changes being detected after storage at 60 °C, 75% relative humidity or exposure to light. The effect of γ-irradiation on the coated rods was also investigated and found to have no significant effect. Finally, liquid chromatography–mass spectrometry analysis revealed that known gentamines C1, C1a and C2 were the major degradants formed. Forced degradation of gentamicin coatings did not produce any unexpected degradants or impurities.

Percutaneous insertion of Dual Growth Rods using a new mobile bearing implant

Growth rods are commonly used for the treatment of scoliosis in the immature spine. Many variations have been proposed but breakage of implants is a common problem. Growth rod insertion commonly involves large exposures at initial insertion followed by multiple smaller procedures for lengthening. We present our early experiences using a percutaneous technique of insertion of a new titanium mobile bearing implant (Medtronic Inc). The implant allows some rotatory motion in the middle of the construct thus reducing construct stresses and thus possibly reducing rod breakage risk. Based on this small initial series with 12 months follow-up, percutaneous insertion of growth rods using the new implant is a safe and reliable technique although the infection rate in our sample was of note. This may be related to the titanium wear and inflammation seen in the soft tissues at time of operation and visualised on histology. No implants have required removal due to infection, and all infections were treated with debridement at next lengthening and suppressive antibiotics. Propionibacterium is one of the commonest infections seen with spinal implants and sometimes does not respond to simple antibiotic suppression. The technique allows preservation of the soft tissues until definitive fusion is needed and may lead to a decrease in hospital stay. The implant is low profile and seems to offer advantages over other systems on the market. Further follow up is needed to look at longer term outcomes with this new implant type.

The measurement of applied forces during anterior single rod correction of adolescent idiopathic scoliosis

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity in paediatrics, prevalent in approximately 2-4% of the general population. While it is a complex three-dimensional deformity, it is clinically characterised by an abnormal lateral curvature of the spine. The treatment for severe deformity is surgical correction with the use of structural implants. Anterior single rod correction employs a solid rod connected to the anterior spine via vertebral body screws. Correction is achieved by applying compression between adjacent vertebral body screws, before locking each screw onto the rod. Biomechanical complication rates have been reported as high as 20.8%, and include rod breakage, screw pull-out and loss of correction. Currently, the corrective forces applied to the spine are unknown. These forces are important variables to consider in understanding the biomechanics of scoliosis correction. The purpose of this study was to measure these forces intra-operatively during anterior single rod AIS correction.

Simulation of the nutrient supply in fracture healing

The healing process for bone fractures is sensitive to mechanical stability and blood supply at the fracture site. Most currently available mechanobiological algorithms of bone healing are based solely on mechanical stimuli, while the explicit analysis of revascularization and its influences on the healing process have not been thoroughly investigated in the literature. In this paper, revascularization was described by two separate processes: angiogenesis and nutrition supply. The mathematical models for angiogenesis and nutrition supply have been proposed and integrated into an existing fuzzy algorithm of fracture healing. The computational algorithm of fracture healing, consisting of stress analysis, analyses of angiogenesis and nutrient supply, and tissue differentiation, has been tested on and compared with animal experimental results published previously. The simulation results showed that, for a small and medium-sized fracture gap, the nutrient supply is sufficient for bone healing, for a large fracture gap, non-union may be induced either by deficient nutrient supply or inadequate mechanical conditions. The comparisons with experimental results demonstrated that the improved computational algorithm is able to simulate a broad spectrum of fracture healing cases and to predict and explain delayed unions and non-union induced by large gap sizes and different mechanical conditions. The new algorithm will allow the simulation of more realistic clinical fracture healing cases with various fracture gaps and geometries and may be helpful to optimise implants and methods for fracture fixation.

Establishment of a preclinical ovine model for tibial segmental bone defect repair by applying bone tissue engineering strategies

Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties, however they are limited in access and availability and associated with donor site morbidity, haemorrhage, risk of infection, insufficient transplant integration, graft devitalisation, and subsequent resorption resulting in decreased mechanical stability. As a result, recent research focuses on the development of alternative therapeutic concepts. The field of tissue engineering has emerged as an important approach to bone regeneration. However, bench to bedside translations are still infrequent as the process towards approval by regulatory bodies is protracted and costly, requiring both comprehensive in vitro and in vivo studies. The subsequent gap between research and clinical translation, hence commercialization, is referred to as the ‘Valley of Death’ and describes a large number of projects and/or ventures that are ceased due to a lack of funding during the transition from product/technology development to regulatory approval and subsequently commercialization. One of the greatest difficulties in bridging the Valley of Death is to develop good manufacturing processes (GMP) and scalable designs and to apply these in pre-clinical studies. In this article, we describe part of the rationale and road map of how our multidisciplinary research team has approached the first steps to translate orthopaedic bone engineering from bench to bedside byestablishing a pre-clinical ovine critical-sized tibial segmental bone defect model and discuss our preliminary data relating to this decisive step.

Computational fluid dynamics for improved bioreactor design and 3D culture

The complex relationship between the hydrodynamic environment and surrounding tissues directly impacts on the design and production of clinically useful grafts and implants. Tissue engineers have generally seen bioreactors as 'black boxes' within which tissue engineering constructs (TECs) are cultured. It is accepted that a more detailed description of fluid mechanics and nutrient transport within process equipment can be achieved by using computational fluid dynamics (CFD) technology. This review discusses applications of CFD for tissue engineering-related bioreactors -- fluid flow processes have direct implications on cellular responses such as attachment, migration and proliferation. We conclude that CFD should be seen as an invaluable tool for analyzing and visualizing the impact of fluidic forces and stresses on cells and TECs.

Enhancing in vivo vascularized bone formation by cobalt chloride-treated bone marrow stromal cells in a tissue engineered periosteum model

The periosteum plays an indispensable role in both bone formation and bone defect healing. In this study we constructed an artificial in vitro periosteum by incorporating osteogenic differentiated bone marrow stromal cells (BMSCs) and cobalt chloride (CoCl(2))-treated BMSCs. The engineered periostea were implanted both subcutaneously and into skull bone defects in SCID mice to investigate ectopic and orthotopic osteogenesis and vascularization. After two weeks in subcutaneous and four weeks in bone defect areas, the implanted constructs were assessed for ectopic and orthotopic osteogenesis and vascularization by micro-CT, histomorphometrical and immunohistochemical methods. The results showed that CoCl(2) pre-treated BMSCs induced higher degree of vascularization and enhanced osteogenesis within the implants in both ectopic and orthotopic areas. This study provided a novel approach using BMSCs sourced from the same patient for both osteogenic and pro-angiogenic purposes in constructing tissue engineered periosteum to enhance vascularized osteogenesis.

FAB-MAP + RatSLAM : appearance-based SLAM for multiple times of day

Appearance-based mapping and localisation is especially challenging when separate processes of mapping and localisation occur at different times of day. The problem is exacerbated in the outdoors where continuous change in sun angle can drastically affect the appearance of a scene. We confront this challenge by fusing the probabilistic local feature based data association method of FAB-MAP with the pose cell filtering and experience mapping of RatSLAM. We evaluate the effectiveness of our amalgamation of methods using five datasets captured throughout the day from a single camera driven through a network of suburban streets. We show further results when the streets are re-visited three weeks later, and draw conclusions on the value of the system for lifelong mapping.

The return of a forgotten polymer : Polycaprolactone in the 21st century

During the resorbable-polymer-boom of the 1970s and 1980s, polycaprolactone (PCL) was used in the biomaterials field and a number of drug-delivery devices. Its popularity was soon superseded by faster resorbable polymers which had fewer perceived disadvantages associated with long term degradation (up to 3-4 years) and intracellular resorption pathways; consequently, PCL was almost forgotten for most of two decades. Recently, a resurgence of interest has propelled PCL back into the biomaterials-arena. The superior rheological and viscoelastic properties over many of its aliphatic polyester counterparts renders PCL easy to manufacture and manipulate into a large range of implants and devices. Coupled with relatively inexpensive production routes and FDA approval, this provides a promising platform for the production of longer-term degradable implants which may be manipulated physically, chemically and biologically to possess tailorable degradation kinetics to suit a specific anatomical site. This review will discuss the application of PCL as a biomaterial over the last two decades focusing on the advantages which have propagated its return into the spotlight with a particular focus on medical devices, drug delivery and tissue engineering.

A Novel Approach to Haptic Tele-operation of Aerial Robot Vehicles

We present a novel, simple and effective approach for tele-operation of aerial robotic vehicles with haptic feedback. Such feedback provides the remote pilot with an intuitive feel of the robot’s state and perceived local environment that will ensure simple and safe operation in cluttered 3D environments common in inspection and surveillance tasks. Our approach is based on energetic considerations and uses the concepts of network theory and port-Hamiltonian systems. We provide a general framework for addressing problems such as mapping the limited stroke of a ‘master’ joystick to the infinite stroke of a ‘slave’ vehicle, while preserving passivity of the closed-loop system in the face of potential time delays in communications links and limited sensor data

Spherical image-based visual servo and structure estimation

This paper presents a formulation of image-based visual servoing (IBVS) for a spherical camera where coordinates are parameterized in terms of colatitude and longitude: IBVSSph. The image Jacobian is derived and simulation results are presented for canonical rotational, translational as well as general motion. Problems with large rotations that affect the planar perspective form of IBVS are not present on the sphere, whereas the desirable robustness properties of IBVS are shown to be retained. We also describe a structure from motion (SfM) system based on camera-centric spherical coordinates and show how a recursive estimator can be used to recover structure. The spherical formulations for IBVS and SfM are particularly suitable for platforms, such as aerial and underwater robots, that move in SE(3).

Physiological investigation of periosteum structure and its application in periosteum tissue engineering

Although many different materials, techniques and methods, including artificial or engineered bone substitutes, have been used to repair various bone defects, the restoration of critical-sized bone defects caused by trauma, surgery or congenital malformation is still a great challenge to orthopedic surgeons. One important fact that has been neglected in the pursuit of resolutions for large bone defect healing is that most physiological bone defect healing needs the periosteum and stripping off the periosteum may result in non-union or non-healed bone defects. Periosteum plays very important roles not only in bone development but also in bone defect healing. The purpose of this project was to construct a functional periosteum in vitro using a single stem cell source and then test its ability to aid the repair of critical-sized bone defect in animal models. This project was designed with three separate but closely-linked parts which in the end led to four independent papers. The first part of this study investigated the structural and cellular features in periostea from diaphyseal and metaphyseal bone surfaces in rats of different ages or with osteoporosis. Histological and immunohistological methods were used in this part of the study. Results revealed that the structure and cell populations in periosteum are both age-related and site-specific. The diaphyseal periosteum showed age-related degeneration, whereas the metaphyseal periosteum is more destructive in older aged rats. The periosteum from osteoporotic bones differs from normal bones both in terms of structure and cell populations. This is especially evident in the cambial layer of the metaphyseal area. Bone resorption appears to be more active in the periosteum from osteoporotic bones, whereas bone formation activity is comparable between the osteoporotic and normal bone. The dysregulation of bone resorption and formation in the periosteum may also be the effect of the interaction between various neural pathways and the cell populations residing within it. One of the most important aspects in periosteum engineering is how to introduce new blood vessels into the engineered periosteum to help form vascularized bone tissues in bone defect areas. The second part of this study was designed to investigate the possibility of differentiating bone marrow stromal cells (BMSCs) into the endothelial cells and using them to construct vascularized periosteum. The endothelial cell differentiation of BMSCs was induced in pro-angiogenic media under both normoxia and CoCl2 (hypoxia-mimicking agent)-induced hypoxia conditions. The VEGF/PEDF expression pattern, endothelial cell specific marker expression, in vitro and in vivo vascularization ability of BMSCs cultured in different situations were assessed. Results revealed that BMSCs most likely cannot be differentiated into endothelial cells through the application of pro-angiogenic growth factors or by culturing under CoCl2-induced hypoxic conditions. However, they may be involved in angiogenesis as regulators under both normoxia and hypoxia conditions. Two major angiogenesis-related growth factors, VEGF (pro-angiogenic) and PEDF (anti-angiogenic) were found to have altered their expressions in accordance with the extracellular environment. BMSCs treated with the hypoxia-mimicking agent CoCl2 expressed more VEGF and less PEDF and enhanced the vascularization of subcutaneous implants in vivo. Based on the findings of the second part, the CoCl2 pre-treated BMSCs were used to construct periosteum, and the in vivo vascularization and osteogenesis of the constructed periosteum were assessed in the third part of this project. The findings of the third part revealed that BMSCs pre-treated with CoCl2 could enhance both ectopic and orthotopic osteogenesis of BMSCs-derived osteoblasts and vascularization at the early osteogenic stage, and the endothelial cells (HUVECs), which were used as positive control, were only capable of promoting osteogenesis after four-weeks. The subcutaneous area of the mouse is most likely inappropriate for assessing new bone formation on collagen scaffolds. This study demonstrated the potential application of CoCl2 pre-treated BMSCs in the tissue engineering not only for periosteum but also bone or other vascularized tissues. In summary, the structure and cell populations in periosteum are age-related, site-specific and closely linked with bone health status. BMSCs as a stem cell source for periosteum engineering are not endothelial cell progenitors but regulators, and CoCl2-treated BMSCs expressed more VEGF and less PEDF. These CoCl2-treated BMSCs enhanced both vascularization and osteogenesis in constructed periosteum transplanted in vivo.