Surface functionalized titanium scaffolds for orthopaedic application: learning from nature

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An accent-independent lexicon for automatic speech recognition.

Recent work at the Centre for Speech Technology Re- search (CSTR) at the University of Edinburgh has de- veloped an accent-independent lexicon for speech synthesis (the Unisyn project). The main purpose of this lexicon is to avoid the problems and cost of writing a new lexicon for every new accent needed for synthesis. Only recently, a first attempt has been made to use the Keyword Lexicon for automatic speech recognition

Design, Production and Characterization of Additive Manufactured Scaffolds for Bone Tissue Engineering (Ontwerp, productie en karakterisatie van laagsgewijs geproduceerde scaffolds voor botweefselengineering)

For the treatment of large or non-healing bone defects, no optimal solution exists to date. All currently available therapies have important drawbacks. To resolve this clinical problem, there is a strong tendency towards regeneration of the bone tissue in the defect. This new approach, called bone tissue engineering (BTE), combines the advantages of autografts and allografts by using cell-seeded porous structures (bone scaffolds), and eliminates problems such as donor site scarcity, immune rejection and pathogen transfer. Despite the tremendous increase of research in this field, no true clinical bone tissue engineering products are available yet. This gap between the amount of research and clinical products can be attributed to the lack of knowledge on bone scaffold key properties and their effect on biological outcome. To obtain this knowledge the production of bone scaffolds with high controllability and repeatability in terms of mechanical and morphological parameters is strongly demanded. Additive manufacturing (AM) techniques are capable of producing porous structures with a controlled architecture, owing to their layer-wise building and direct link with a computer aided design (CAD) model. This will allow the production of scaffolds with tailored structural properties which can be used to investigate their biological outcome. The general aim of this PhD study was to develop a robust production protocol consisting of a design step, AM technique and characterization methods to produce both biodegradable polycaprolactone (PCL) and bio-inert Ti6Al4V scaffolds with a highly controlled internal porous architecture. Furthermore, the research described in this dissertation aimed at answering following three questions: 1. Can we produce bone scaffolds with controlled mechanical and morphological properties?2. Can we use the controlled SLM process to evaluate morphological and mechanical influencing parameters of bone scaffolds?3. Can we alter the surface chemistry of Ti6Al4V and PCL bone scaffolds to improve their in-vitro cell performance? The research described in this dissertation resulted in two robust AM techniques, namely selective laser sintering (SLS) and selective laser melting (SLM), for the production of biodegradable PCL and Ti6Al4V bone scaffolds with controlled morphological and mechanical properties. By using the controlled Ti6Al4V scaffolds a first step was taken in evaluating the effect of key design parameters on the behavior of in-vitro osteogenic cell behavior. The results achieved in this dissertation directly lead to a novel hypothesis suggesting that a thoroughly defined gradient architecture produced with a robust AM technique might improve cell seeding and proliferation, which can be used in further research. Finally, as the surface chemistry cannot be altered during the AM production process, different surface post-treatment steps were used to successfully alter the surface chemistry of the as-produced PCL and Ti6Al4V scaffolds. In conclusion, this PhD study shows that the AM techniques SLS and SLM can be useful to produce highly porous bone scaffolds with repeatable and controllable morphological and mechanical properties. Subsequently, these controllable bone scaffolds can be used for post-treatment, in-vitro and in-vivo experiments.status: publishe

In vivo ectopic bone formation by devitalized mineralized stem cell carriers produced under mineralizing culture condition.

Functionalization of tissue engineering scaffolds with in vitro-generated bone-like extracellular matrix (ECM) represents an effective biomimetic approach to promote osteogenic differentiation of stem cells in vitro. However, the bone-forming capacity of these constructs (seeded with or without cells) is so far not apparent. In this study, we aimed at developing a mineralizing culture condition to biofunctionalize three-dimensional (3D) porous scaffolds with highly mineralized ECM in order to produce devitalized, osteoinductive mineralized carriers for human periosteal-derived progenitors (hPDCs). For this, three medium formulations [i.e., growth medium only (BM1), with ascorbic acid (BM2), and with ascorbic acid and dexamethasone (BM3)] supplemented with calcium (Ca(2+)) and phosphate (PO4 (3-)) ions simultaneously as mineralizing source were investigated. The results showed that, besides the significant impacts on enhancing cell proliferation (the highest in BM3 condition), the formulated mineralizing media differentially regulated the osteochondro-related gene markers in a medium-dependent manner (e.g., significant upregulation of BMP2, bone sialoprotein, osteocalcin, and Wnt5a in BM2 condition). This has resulted in distinguished cell populations that were identifiable by specific gene signatures as demonstrated by the principle component analysis. Through devitalization, mineralized carriers with apatite crystal structures unique to each medium condition (by X-ray diffraction and SEM analysis) were obtained. Quantitatively, BM3 condition produced carriers with the highest mineral and collagen contents as well as human-specific VEGF proteins, followed by BM2 and BM1 conditions. Encouragingly, all mineralized carriers (after reseeded with hPDCs) induced bone formation after 8 weeks of subcutaneous implantation in nude mice models, with BM2-carriers inducing the highest bone volume, and the lowest in the BM3 condition (as quantitated by nano-computed tomography [nano-CT]). Histological analysis revealed different bone formation patterns, either bone ossicles containing bone marrow surrounding the scaffold struts (in BM2) or bone apposition directly on the struts' surface (in BM1 and BM3). In conclusion, we have presented experimental data on the feasibility to produce devitalized osteoinductive mineralized carriers by functionalizing 3D porous scaffolds with an in vitro cell-made mineralized matrix under the mineralizing culture conditions

Investigation of the influence of surface roughness modification of bone tissue engineering scaffolds

status: publishe