Biomaterials Contact persons :Jan Van Humbeeck, Jan Schrooten Industrial Research fellow Biomaterials & Tissue Engineering Jan Schrooten The Industrial Research Fellow is a mandate that envisions a long-term strategy for Biomaterials & Tissue Engineering at the KULeuven, with an initial focus on bone regeneration. In order to realise this goal an interdisciplinary organisation, that brings together researchers from material science, biology, biomechanics, polymer chemistry, bio-informatics, physics, mathematics and also surgeons, needs to be build up. This mandate wants to take the first step towards this interdisciplinary organised research that eventually should lead to clinically relevant bone tissue regeneration. With time this knowledge can be extrapolated to other tissues, thus allowing medical science to evolve from organ transplantation towards organ production. IOF website Guided Bone Engineering. Healing of large bone defects. Jan Schrooten, Jan Van Humbeeck, Saartje Impen This project uses a tissue engineering approach to develop repair systems for large defects in load bearing parts of the skeleton. The project is embedded in a larger framework to gather generic knowledge on tissue engineering through an interdisciplinary approach. This approach is visible through the research partners involved: MTM (KULeuven), Division of Biomechanics and Engineering design (KULeuven), Laboratory of skeletal development and joint disorders (KULeuven), Polymer Materials Research Group (UGent) and Ceramic Processing and Powder Metallurgy (VITO). Also several major industrial and medical actors in Flanders support this project. This project will be the basis for future tissue engineering projects in Flanders and for the training of tissue engineers. Guided bone regeneration requires a close collaboration between three disciplines: biology, biomaterials and biomechanics. Only through the integration of these three research disciplines, which has not been realised yet, a suitable solution for the healing of large bone defects can be found. GBE website Quantitative Engineering of Skeletal Tissues (QuEST) Jan Schrooten This project, officially entitled “Development and quantitative evaluation of in vitro and in vivo three dimensional environments for clinically relevant osteoinductive tissue engineering constructs”, is a partnership between the faculties of Engineering, Bio-engineering and Medicine and is part of the interdisciplinary tissue engineering program. The project aims to develop a quantitative 3D environment for bone tissue engineering constructs, by combining scaffolds, cells and biological compounds in a controlled bioreactor environment, allowing the development of reproducible TE-constructs. Specific tasks include (i) long-term TE-planning, (ii) production of consistent scaffolds, (iii) biological functionalisation of scaffolds, (iv) control of stem cell behaviour in a 3D bioreactor, (v) bioreactor culturing, and (vi) in vivo experiments in different animal models. Screening of 3D bone scaffolds with the aid of a perfusion bioreactor Jan Schrooten, Jan Van Humbeeck, Saartje Impens In order to bring bone tissue engineering closer to clinical reality, bioactive scaffolds are required. Ideally these scaffolds should stimulate proliferation and differentiation of adherent stem cells towards osteoblast like cells. The bio-activation of scaffolds is done by specific surface modifications combined with the addition of growth factors, all prior to cell seeding. To allow a controlled and reproducible 3D cell culture process, the seeding and culture processes are performed within a perfusion bioreactor. This bioreactor will be equipped with sensors to monitor and control the cell behaviour on line. Development of porous biomaterials for the healing of large bone defects Jan Schrooten, Jan Van Humbeeck, Wouter Vandessel At this moment there is no optimal solution for the repair of large bone defects (>3 cm). The problem is the lack of a suitable porous scaffold. The goal of this research is the production of these porous structures. Interdisciplinarity between biology, biomechanics and material science is important to avoid trial and error as much as possible. The structures should meet the biological, biomechanical and material demands. The porous structures will be produced by gel-casting and replica method. Also a protocol will be developed and applied to evaluate the structures. This work is part of the Guided Bone Engineering project. Functional coatings for advanced optical sensors Jan Schrooten Sensor technology is a multidisciplinary field of research in which the interaction between (bio)materials and electronics is crucial. Sensors are essential in a lot of industrial (process control) and medical (diagnostics) applications. This research project exclusively envisions the development of new optical sensors. The amount of optical sensors in industry and medicine has increased a lot over the last few years, because of lower development and production costs, and because of the higher sensitivity of this type of sensors. The selection of a ‘sensitive’ material is crucial for the development of a new sensor, thus a first goal of this project is the development of new functional coatings for sensors for industrial and medical applications. The present generation of optical sensors only has a sensitive layer at the tip of sensor, resulting in a slow response and a limited sensitivity. Thus a second goal of this project the development of a technology that allows to detect the response of a functional coating along the surface of the optical fibre. Science-driven formulation of pharmacologic active compounds with problematic physiochemical properties (FORMAC) Jan Van Humbeeck, Jan Schrooten The FORMAC project wants to tackle a shortcoming of the scientific tools used today to accomplish optimal formulation for poorly soluble drugs. One of the implications of combinatorial chemistry and in silico drug design used during drug discovery is the increased molecular complexity leading to potent and selective compounds often with aqueous solubility that is too low to allow the development to a marketable drug. Clearly, it is crucial to evaluate as soon as possible during the discovery/development process the potential of a compound with respect to its formulate-ability. Scientific knowledge must be gained in order to evaluate if a compound can be formulated and developed to a stable commercial drug with adequate and reproducible systemic exposure. There exists a wide variety of possible formulation strategies to improve bioavailability and stability but today, the formulation process of poorly soluble compounds is still driven by trial and error. This is an expensive and time consuming process since all possible formulation strategies need to be explored, without guarantee for eventual success. The realisation of the scientific goals necessitates a multidisciplinary consortium, with expertise in pharmaceutical technology, biopharmaceutics, material science, and colloid chemistry. Optimisation of osteogenesis with titanium membranes using osteogenic cell populations, mechanical stimulation and bioactive coatings. Jan Schrooten, Jan Van Humbeeck Autologous bone grafting is still the golden standard for bone augmentation in clinics. Morbidity at the donor site, availability, general anesthesia and the poor predictability of resorptive events are among the limitations of this technique. This project envisions to develop more efficient clinical protocols for new bone formation, in particular alveolar ridge augmentation. The potential synergy between precursor cell technology, biomechanics and material sciences for optimal bone formation under titanium membranes will be explored. The KULeuven research partners involved are the following: Laboratory of skeletal development and joint disorders, Department of Dentistry, Prosthetic Dentistry, Department of Dentistry, Periodontology, Division of Biomechanics and Engineering design and MTM. In vitro corrosion behavior of porous nitinol medical devices Jan Schrooten, Jan Van Humbeeck Porous nitinol is produced by Biorthex Inc. (Montreal, QC, Canada) and represents a new biomaterial for long-term hard tissue implantation. This bulk structural porous material is in fact produced via a layerwise reaction of compacted nearly-equiatomic nickel and titanium powders after preheating toward the required temperature. The result is a biomaterial with a complete interconnected void volume porosity percentage of 64 ± 4% and pore size diameters of 215 ± 104mm. This type of porosity was shown to trigger fluid capillarity without the need to exert external hydraulic forces. Therefore, porous nitinol has been projected for use in many clinical applications where osseointegration is necessary including long-term intervertebral fusion implants. Porous nitinol biocompatibility and more precisely its corrosion resistance evaluation were investigated in this study. In particular, porous nitinol was evaluated under potentiodynamic polarization. In parallel, porous nitinol was additionally tested for its galvanic corrosion resistance in presence of titanium alloys. Porous nitinol cervical intervertebral fusion implants (Biorthex Inc., Montreal, QC, Canada). Metallic cardiovascular stents Jan Van Humbeeck, Zhao Hui, Ludo Froyen A stent is a medical device that can provide an endovascular scaffolding to relieve vascular obstruction. Endovascular prosthesis (stent) has been developed for more than twenty years and nowadays it has been becoming very popular in the treatment of obstructive vascular disease, especially coronary artery disease. The surface of a stent is the interface between the stent and both vascular tissue and blood. The surface status of stents influences their biocompatibility, the nature of immediate and long-term response after implantation of stents. Surface treatment by electrochemical polishing of stainless steel slotted tube stents to improve their biocompatibility was explored in our group. The work consists of the process optimization, as well as the material removal and surface roughness evaluation. Corrosion and fatigue properties were also evaluated. Moreover, medical evaluation in a pig coronary artery model was performed as well. In addition, the study was focused on heat affected zone caused by laser cutting, removal of cutting products by pickling as well as electrochemical polishing of nitinol slotted tube stents. The work consists of optimization, material removal and surface roughness evaluation of pickling and electrochemical polishing. Mechanical and transformation properties of the nitinol were also investigated. This work is conducted in colllaboration with the Department of Cardiology (KULeuven), Precision Cutting Systems NV and Flexmet. SEM pictures of stainless steel slotted tube stents: a non-polished stent (left) and an polished stent (right). Drug eluting cardiovascular stents Jan Van Humbeeck, Jan Schrooten, Zhao Hu A new stent design has been developed to improve drug delivery. The stent contains small pits, which can contain appropriate drugs. Biocompatibilty tests in pig models and specific fatigue testing has shown that those stents have similar characteristics as the usual good stents. Further research is now done on controlling the rate of drug delivery. The KULeuven research partners are the following: MTM, Department of Interphase Chemistry and Department of Cardiology. Advanced dental implants manufactured by selective laser sintering Ludo Froyen, Jan Van Humbeeck The main objective is to develop new dental implants which have a high bio-compatibility both at the post-operational stage and over a further long period (for many years) of human organism's functioning and, in addition, do not cause any pain to the patient during the operation of implantation. Therefore, tooth's root implants of titanium which will most correspond to natural tooth's roots, will be developed. The manufacturing method is by selective laser sintering. The physical foundations of the developed methods and in particular the mechanisms of laser particular radiation interaction with the metal powders will be studied. The correlation between the laser processing parameters and the resulting structure and properties of the developed implants will be determined. Innovative Coating of Temperature Sensitive Medical Implants with Biofunctional Materials Using Electron Beam Ablation (INCOMED) Jan Schrooten, Jan Van Humbeeck Sometimes it comes to complications with the biocompatible materials. Fibrous tissue encapsulation of the implant leads to inflammations followed by final repulsion. The consequences for the patient are additional operations and rehabilitation programmes. With increased age of patients this becomes more complicated and more dangerous. In the area of the transcutaneuos body access (catheter) it is not yet possible to succeed with intergrow of living tissue with implant in such a way that complications such as infections, inflammations and undesired grains do not occur. At present it is already possible to coat temperature in-sensitive materials like metals with biocompatible materials and succeed with tissue intergrow. This is done with thin layers of bioactive materials, such as hydroxyapatite or bioactive glasses by thermal processes, like plasmaspraying or dipping into melt. Temperature sensitive materials such as plastics or coating materials with complex stoichiometric composition cannot be coated with the today usual procedures. However, with the method of the electron beam ablation (ELBA) sensitive materials can be coated, since the thermal load can be reduced to a minimum. This allows the use of new materials which up to now could not be implanted. In addition new material combinations are possible which enables to build new types of implants. The advantages in comparison with conventional methods are not least a simpler coating process, which allows a more efficient operation. This European project also involves FZK-IHM (Germany) and BMGO-KULeuven (Belgium) as research partners and BIOMATECH (France), GB-Implantat (Germany) and TEER Coatings (UK) as industrial partners. INCOMED website

 

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