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Lorenz, T.

Publications and source records attributed to Lorenz, T..

2 recordsLinked to original sources

Fluid-Structure Interactions of Peripheral Arteries Using a Coupled in silico and in vitro Approach

Vascular compliance is considered both a cause and a consequence of cardiovascular disease and a significant factor in the mid- and long-term patency of vascular grafts. However, the biomechanical effects of localised changes in compliance, such as during plaque development or after bypass grafting and stenting, cannot be satisfactorily studied with the available medical imaging technologies or surgical simulation materials. To address this unmet need, we developed a coupled silico-vitro platform which allows for the validation of numerical fluid-structure interaction (FSI) results as a numerical model and physical prototype. This numerical one-way and two-way FSI study is based on a three-dimensional computer model of an idealised femoral artery which is validated against patient measurements derived from the literature. The numerical results are then compared with experimental values collected from compliant arterial phantoms. Phantoms within a compliance range of 1.4 - 68.0%/100mmHg were fabricated via additive manufacturing and silicone casting, then mechanically characterised via ring tensile testing and optical analysis under direct pressurisation with differences in measured compliance ranging between 10 - 20% for the two methods. One-way FSI coupling underestimated arterial wall compliance by up to 14.71% compared to two-way FSI modelling. Overall, Smooth-On Solaris matched the compliance range of the numerical and in vivo patient models most closely out of the tested silicone materials. Our approach is promising for vascular applications where mechanical compliance is especially important, such as the study of diseases which commonly affect arterial wall stiffness, such as atherosclerosis, and the model-based design, surgical training, and optimisation of vascular prostheses.

bioengineering↗

Stable Protein Sialylation in Physcomitrella

Recombinantly produced proteins are indispensable tools for medical applications. Since the majority of them are glycoproteins, their N-glycosylation profiles are major determinants for their activity, structural properties and safety. For therapeutical applications, a glycosylation pattern adapted to product and treatment requirements is advantageous. Physcomitrella (Physcomitrium patens, moss) is able to perform highly homogeneous complex-type N-glycosylation. Additionally, it has been glyco-engineered to eliminate plant-specific sugar residues by knock-out of the {beta}1,2-xylosyltransferase and 1,3-fucosyltransferase genes ({Delta}xt/ft). Furthermore, P. patens meets wide-ranging biopharmaceutical requirements such as GMP compliance, product safety, scalability and outstanding possibilities for precise genome engineering. However, all plants, in contrast to mammals, lack the capability to perform N-glycan sialylation. Since sialic acids are a common terminal modification on human N-glycans, the property to perform N-glycan sialylation is highly desired within the plant-based biopharmaceutical sector. In this study, we present the successful achievement of protein N-glycan sialylation in stably transformed P. patens. The sialylation ability was achieved in a {Delta}xt/ft moss line by stable expression of six mammalian coding sequences combined with targeted organelle-specific localization of the encoded enzymes responsible for synthesis, activation, transport and transfer of sialic acid. Production of free and (CMP)-activated sialic acid was proven. The glycosidic anchor for the attachment of terminal sialic acid was generated by the introduction of a chimeric human {beta}1,4-galactosyltransferase gene under the simultaneous knock-out of the gene encoding the endogenous {beta}1,3-galactosyltransferase. Functional complex-type N-glycan sialylation was confirmed via mass spectrometric analysis of a stably co-expressed recombinant human protein.

bioengineering↗