Stefan Jockenhövel

FMN-coated fluorescent USPIO for cell labeling and non-invasive MR imaging in tissue engineering

Non-invasive magnetic resonance imaging (MRI) is gaining significant attention in the field of tissue engineering, since it can provide valuable information on in vitro production parameters and in vivo performance. It can e.g. be used to monitor the morphology, location and function of the regenerated tissue, the integrity, remodeling and resorption of the scaffold, and the fate of the implanted cells. Since cells are not visible using conventional MR techniques, ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are routinely employed to label and monitor the cells embedded in tissue-engineered implants. We here set out to optimize cell labeling procedures with regard to labeling efficiency, biocompatibility and in vitro validation during bioreactor cultivation, using flavin mononucleotide (FMN)-coated fluorescent USPIO (FLUSPIO). Efficient FLUSPIO uptake is demonstrated in three different cell lines, applying relatively short incubation times and low labeling concentrations. FLUSPIO-labeled cells were successfully employed to visualize collagen scaffolds and tissue-engineered vascular grafts. Besides promoting safe and efficient cell uptake, an exquisite property of the non-polymeric FMN-coating is that it renders the USPIO fluorescent, providing a means for in vitro, in vivo and ex vivo validation via fluorescence microscopy and fluorescence reflectance imaging (FRI). FLUSPIO cell labeling is consequently considered to be a suitable tool for theranostic tissue engineering purposes.

Characterisation of cell-substrate interactions between Schwann cells and three-dimensional fibrin hydrogels containing orientated nanofibre topographical cues.

The generation of complex three‐dimensional bioengineered scaffolds that are capable of mimicking the molecular and topographical cues of the extracellular matrix found in native tissues is a field of expanding research. The systematic development of such scaffolds requires the characterisation of cell behaviour in response to the individual components of the scaffold. In the present investigation, we studied cell–substrate interactions between purified populations of Schwann cells and three‐dimensional fibrin hydrogel scaffolds, in the presence or absence of multiple layers of highly orientated electrospun polycaprolactone nanofibres. Embedded Schwann cells remained viable within the fibrin hydrogel for up to 7 days (the longest time studied); however, cell behaviour in the hydrogel was somewhat different to that observed on the two‐dimensional fibrin substrate: Schwann cells failed to proliferate in the fibrin hydrogel, whereas cell numbers increased steadily on the two‐dimensional fibrin substrate. Schwann cells within the fibrin hydrogel developed complex process branching patterns, but, when presented with orientated nanofibres, showed a strong tendency to redistribute themselves onto the nanofibres, where they extended long processes that followed the longitudinal orientation of the nanofibres. The process length along nanofibre‐containing fibrin hydrogel reached near‐maximal levels (for the present experimental conditions) as early as 1 day after culturing. The ability of this three‐dimensional, extracellular matrix‐mimicking scaffold to support Schwann cell survival and provide topographical cues for rapid process extension suggest that it may be an appropriate device design for the bridging of experimental lesions of the peripheral nervous system.

Targeting In-Stent-Stenosis with RGD- and CXCL1-Coated Mini-Stents in Mice

Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol-stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice. Nitinol foils or stents (bare metal) were coated with star-PEG, and bio-functionalized with RGD, or RGD/CXCL1. Cell adhesion to star-PEG-coated nitinol foils was unaltered or reduced, whereas bio-functionalization with RGD but foremost RGD/CXCL1 increased adhesion of early angiogenic outgrowth cells (EOCs) and endothelial cells but not smooth muscle cells when compared with bare metal foils. Stimulation of cells with RGD/CXCL1 furthermore increased the proliferation of EOCs. In vivo, bio-functionalization with RGD/CXCL1 significantly reduced neointima formation and thrombus formation, and increased re-endothelialization in apoE-/- carotid arteries compared with bare-metal nitinol stents, star-PEG-coated stents, and stents bio-functionalized with RGD only. Bio-functionalization of star-PEG-coated nitinol-stents with RGD/CXCL1 reduced in-stent neointima formation. By supporting the adhesion and proliferation of endothelial progenitor cells, RGD/CXCL1 coating of stents may help to accelerate endothelial repair after stent implantation, and thus may harbor the potential to limit the complication of in-stent restenosis in clinical approaches.

Design and Manufacture of Textile-Based Sensors

The textile and clothing industry in Europe has intensively changed in relocation of production facilities to low-wage countries. To preserve the leading role in global markets, the European activities are focused more on creative fashion design, quality and innovation. The textile and clothing industry is split into clothing (46%), home and interior (32%) and the technical sector (22%) and still represents the major industrial fields. In all three sectors are new applications with functionalized textiles, called ‘smart textiles’. Taking a look at our modern environment, it can be seen that people carry more electronic supplements than ever. Clothing with adapted electronics, such as MP3 players and cameras, is already marketed. Adapting rigid electronic components to soft and flexible textiles is not attractive for the end user. So textile-based control panels are customised regarding wearability and comfortability. Because textiles are made of fibres, yarns or two- or three-dimensional structures, the sensor systems should be designed as a part of them accordingly. The development of a textile sensor and its interpretation of a specific application have been associated with many investigations into combinations of different conductive materials, which are lengthy and costly research processes. Knowledge has already been generated on textile sensors, which now require an appropriate classification and structure. To reduce the gap between research and industry knowledge in smart textiles, a classified catalogue, which allows a direct selection of textile-based sensor modules, and a methodical approach, the smart 7-step tool for developing textile-based sensors in different application fields, have been developed.

Classified Catalogue for Textile Based Sensors

Technical textiles are used primarily for their technical functionality in many different industries. For monitoring the functionality of textiles it is possible to integrate sensors into the textile. Since textiles are made of fibres, yarns, two-or three dimensional structures the sensor systems should accordingly be designed as a part of them. Smart textiles are concerned with textile based sensors integrated mechanically and structurally to a textile. The state of the art in developing textile based sensors extends from sensor fibres to over coated yarns and textiles but without using standardized tools. The development of a textile sensor and its interpretation on a specific application has been associated with many investigations into combination of different conductive materials, what is a lengthy and costly developing process. Knowledge has already been generated on textile sensors, which now requires an appropriate classification and structure. A classified catalogue which allows a direct selection of textile based sensor modules on the basis of measured values. The catalogue´s structure follows, apart from the VDI- guideline 2222, of which complex coherences can be arranged and a clear representation can be found. Setting standards in the field of smart textiles helps companies to produce more smart products.

Development of a Polymer-Based Biodegradable Neurovascular Stent Prototype: A Preliminary In Vitro and In Vivo Study

Biodegradable stents are not established in neurovascular interventions. In this study, mechanical, radiological, and histological characteristics of a stent prototype developed for neurovascular use are presented. The elasticity and brittleness of PLA 96/4, PLDL 70/30, PCL, and PLGA 85/15 and 10/90 polymers in in vitro experiments are first analyzed. After excluding the inapt polymers, degradability and mechanical characteristics of 78 PLGA 85/15 and PLGA 10/90 stent prototypes are analyzed. After excluding PLGA 10/90 stents because of rapid loss of mass PLGA 85/15 stents in porcine in vivo experiments are analyzed. Angiographic occlusion rates 7 d, 1 month, 3 months, and 6 months after stent implantation are assessed. Histological outcome measures are the presence of signs of inflammation, endothelialization, and the homogeneity of degradation after six months. One case of stent occlusion occurs within the first 7 d. There is a prominent foreign-body reaction with considerable mononuclear and minor granulocytic inflammation combined with incomplete fragmental degradation of the struts. It is possible to produce a stent prototype with dimensions that fit the typical size of carotid arteries. Major improvements concerning thrombogenicity, degradation, and inflammatory response are required to produce biodegradable stents that are suitable for neurovascular interventions.

Fluid-structure interaction simulation of artificial textile reinforced aortic heart valve: Validation with an in-vitro test

Prosthetic heart valves deployed in the left heart (aortic and mitral) are subjected to harsh hemodynamical conditions. Most of the tissue engineered heart valves have been developed for the low pressure pulmonary position because of the difficulties in fabricating a mechanically strong valve, able to withstand the systemic circulation. This necessitates the use of reinforcing scaffolds, resulting in a tissue-engineered textile reinforced tubular aortic heart valve. Therefore, to better design these implants, material behaviour of the composite, valve kinematics and its hemodynamical response need to be evaluated. Experimental assessment can be immensely time consuming and expensive, paving way for numerical studies. In this work, the material properties obtained using the previously proposed multi-scale numerical method for textile composites was evaluated for its accuracy. An in silico immersed boundary (IB) fluid structure interaction (FSI) simulation emulating the in vitro experiment was set-up to evaluate and compare the geometric orifice area and flow rate for one beat cycle. Results from the in silico FSI simulation were found to be in good coherence with the in vitro test during the systolic phase, while mean deviation of approximately 9% was observed during the diastolic phase of a beat cycle. Merits and demerits of the in silico IB-FSI method for the presented case study has been discussed with the advantages outweighing the drawbacks, indicating the potential towards an effective use of this framework in the development and analysis of heart valves.

Combining material and structural elasticity - An approach to enhanced compliance of small-calibre vascular grafts

Up to date, commercially available vascular grafts for the replacement of diseased small calibre artery segments (d ≤ 6 mm) show low patency rates. One of the commonly named causes in literature is a low radial elasticity of the vascular graft, compared to that of the native vessel. At the Institut für Textiltechnik of RWTH Aachen University, a new approach combining elastic and non-elastic yarns in the warp knitting process is used for the production of vascular grafts. This unique combination of materialand structural elasticity is used to better model the compliance of native vessels and thus increase the patency rates of synthetic vascular grafts.The first section in your paper

Werkstoffe/Biomaterialien in der interventionellen und operativen Medizin – eine kurze Übersicht und aktuelle Trends

Biomaterials play a major role in interventional medicine and surgery. However, the development of biomaterials is still in its early phases in spite of the huge progress made within the last decades. On the one hand, this is because our knowledge of the molecular and cellular processes associated with biomaterials is still increasing exponentially. On the other hand, a wide variety of advanced materials with highly interesting properties is being developed currently. This review provides a short introduction into the variety of materials in use as well as their application in interventional medicine and surgery. Also the importance of biomaterials for tissue engineering in the field of regenerative medicine and the functionalisation of biomaterials, including sterilisation methods are discussed. For the future, an even broader interdisciplinary scientific collaboration is necessary in order to develop novel biomaterials and facilitate their translation into clinical practice.