29. Jahrestagung der Deutschen Gesellschaft für Biomaterialien

Prof. Dr.

Chair

Biofabrication of hybrid tubular constructs with adjusted mechanical properties for the development of small diameter vascular tissue models

Biofabrication

Additive manufacturing (e. g. 3D printing)

Abstract text (incl. figure legends and references) In the human body, tubular structures like the vascular or lymphatic systems are abundant. Since Biofabrication aims to mimic the hierarchy of natural tissues to improve the performance of biofabricated constructs, tubular geometries are highly relevant. Biofabricated tissue models should not only mimic the macroscopic structure and shape but also the microarchitecture of the tissue they replace. Besides the architecture, the biomechanics of the tissues should also be considered and tailored to the needs of the tissues models they are envisioned for. Taking these design criteria into account enables the generation of models with improved function and tissue specificity. The objective of this work is to identify and demonstrate the compatibility of the combination of different fabrication techniques to generate tubular constructs with advanced properties for the generation of tissue models. To produce fiber-reinforces tubular hydrogel constructs, we combined the novel bioprinting technology of volumetric printing with melt electrowriting (MEW). We could show that we can print structures around the tubes and make complex multi-material cell-laden constructs. Bi-layered biomimetic tubular constructs are fabricated via a combination of solution electrospinning (solES) and MEW. To fine tune the mechanical properties of these scaffolds, several combinations of materials - PCL, poly(ester urethane) (PEU), acrylate-endcapped urethane-based PCL and blends of these - are used for solES to influence the over-all properties of the grafts. The mechanical properties of the cell seeded constructs are compared and adjusted to match the values of human tissues. In conclusion, this presentation is demonstrating how the combination of different fabrication methods can be used to make hierarchical multi-layered tubular constructs with biomimetic architectures and adjustable mechanical properties.

Short Talk

Melt electrowriting and its applications in biofabrication for the generation of synthetic tubular constructs with defined mechanical characteristics

Tissue regeneration/regenerated medicine

Abstract text (incl. figure legends and references) Intro The need for new approaches to generate small diameter vascular constructs is still significant, as now only autograft transplants are successfully used as treatment method. Reason for this is a quick onset of occlusion within the scaffold via thrombus formation after implantation. A core factor is a mechanical mismatch of the synthetic graft and the blood vessel it is grafted onto. New strategies to generate mechanics-matched constructs are direly needed. Objectives Melt Electrowriting (MEW) onto a tubular collector allows for the generation of tubular reinforcement lattice structures, that can be used in conjunction with other techniques to generate heterotypic scaffolds with adaptable mechanical characteristics. The ability to modulate the mechanics of MEW tubes via geometrical features lends itself to quickly change the mechanics of constructs depending on the intended application. Materials &amp; Methods A custom MEW printer has been employed to generate different tubular constructs that could be pre modified via compounding or later allowed for the change of mechanical response, depending on layer height and geometry. Combining constructs with solution electrospun (SES) scaffolds or volumetrically printed hydrogels allowed the generation of tubular constructs with varying mechanical responses. Results The generation of SES and MEW tubes with cells seeded onto them allowed to closely mimic the mechanics of different human biopsy samples of relevant autograft vessel types. In conjunction with volumetric printing of GelMA, coronary vessels of porcine origin could be mechanically approximated. Conclusion Convergence of different fabrication techniques is forming to be the next big frontier in the field of biofabrication. MEW tubes combined with other methods already demonstrate the potential that convergence can bring towards a better recreation of blood vessel mechanics than what was possible before Fig.1 Stress/Strain of MEW/SES construct vs vessel

Electrospinning as a versatile platform for the fabrication of prosthetic venous valves

Abstract text (incl. figure legends and references) Introduction Chronic venous insufficiency (CVI) is a widespread chronic disease that can be caused by venous valves malfunction. The treatment of CVI with deep venous reflux remains a challenge with few therapy options. A prosthetic venous valve (PVV) that replaces the native diseased one could be a solution, however, despite extensive research, there is no commercially available PVV. Objectives This study aims to fabricate mono-, bi-, and tri-leaflet PVVs by electrospinning, positioned in commercially available venous stents. Materials &amp; methods A thermoplastic polyurethane solution is electro spun onto an additive manufactured mold forming the leaflet sleeve. Further, the leaflet free edge is manually cut and the sleeve is positioned in a venous stent. During a next step, a connection between both structures is achieved. The fluid-dynamic behavior of the produced PVVs is evaluated in a flow loop system under physiological flow and pressure conditions. Main functional parameters such as transvalvular pressure drop, regurgitant fraction and effective orifice area are measured. Further, durably tests are carried out. Results The study shows that PVV of different diameter ranging form 6 mm to 14 mm can be produced using electrospinning and secured to the stent. The hemodynamic characterization indicates that low transvalvular pressure drops and regurgitation fraction can be achieved by the electrospun PVV. Conclusion The study shows that electrospinning is a versatile platform to equip commercial venous stents with small prosthetic valves. The produced percutaneous venous valve implant showed good in vitro behavior and could be suitable to treat deep venous reflux.

Two-photon-stereolithography of biosynthetic and cell-interactive microstructures for versatile tissue engineering applications

Cell-material interactions

Abstract text (incl. figure legends and references) Two-Photon-Stereolithography (TPS) is a high resolution 3D-printing methods that enables the fabrication of miniaturized constructs with micro- to nanometer sized features. Recent progress in material development enabled the application of cytocompatible resins that can be used to generate biosynthetic cell-material interfaces with controllable microstructural properties. The aim of this work was to investigate the general performance of the process and its potential to generate cell-culture supporting and cell-interactive 3D-structures. To study the general performance of the TPS system the minimal achievable feature and void sizes and biocompatibility were accessed for two different resin materials (methacrylate based polymers). Next, to demonstrate the broad applicability of the technology, three different biosynthetic and cell-interactive microstructures were generated: capillary vessel mimicking tubes, cell-entrapping self-folding carpets, and multicellular spheroid-wrapping cages. Capillary vessel mimicking tubes (10 µm to 2 mm in diameter) could fabricated. To allow biosynthetic interaction with the surrounding matrix, micropores (1-50 µm in diameter) that promote the permeability of biomolecules were integrated. Diffusion of FITC-labeled dextran into an aqueous environment as well as into surrounding hydrogel matrices could be confirmed. Next, cell-entrapping, self-folding thin sheets (5 µm) were fabricated and seeded with cells. By applying a temperature gradient, folding of the sheets into tubular structures (40 - 60 µm ID) that entrapped the cells could be initiated. Ultimately, spherical cages (300 µm OD) with integrated capillary tubes were generated and used for the cultivation of cell-spheroids. The results of this work demonstrate the general strength of TPS for the fabrication of biosynthetic and cell-interactive microstructures. The broad applicability holds great promise for future research in tissue engineering and synthetic biology.

Professor

Shape-morphing fibre composite structures consisting of 3D plotted hydrogels and melt electrowritten PCL meshes for blood vessel tissue engineering

Abstract text (incl. figure legends and references) Introduction The requirements for artificial blood vessels are manifold: they have to be dense and mechanically stable tubular structures, they have to allow the formation of an endothelial cell monolayer on the inside and - importantly for surgical applications – they must be suturable. The objective of this work was to develop a fabrication process for integration of polycaprolactone (PCL) meshes into a 4D printing process of an alginate/methylcellulose-based hydrogel by combining melt electrowriting (MEW) and 3D plotting and to characterize the composite structures. Materials &amp; methods MEW of PCL (Purasorb PC12 Corbion) meshes was performed with a GeSiM BioScaffolder 3.1 combined with a MEW head as described previously [1]. A blend of 3% alginate and 9% methylcellulose was used for 3D plotting with the BioScaffolder (first layer without gap between the parallel strands; second and third layer on top of each other with varying distances between the parallel strands). After air-drying, shape-morphing into tubes was induced by immersion into CaCl2-solution followed by freeze drying. The samples were characterized by tensile test, sewing and perfusion test, microscopic analyses and cell seeding experiments with human fibroblasts and endothelial cells. Results Tubular structures with diameters of 2-5 mm were generated; the PCL meshes could be integrated without inhibiting the shape morphing effect. The composite structures containing PCL meshes exhibited a higher tensile strength compared to the pure hydrogel structures. Moreover, the integration of PCL meshes resulted in tubes which are sewable and could be perfused without leakage. Finally, the composite structures were successfully seeded with cells. Conclusion The feasibility of this multi-step fabrication process of a self-assembling fibre-hydrogel composite tubular structure was demonstrated which is potentially applicable for blood vessel tissue engineering. [1] von Witzleben et al. 2021, doi.org/10.1002/adhm.202002089

Short Talks 10
Biofabrication / Artificial Vascular Structures

Termin

Chair

Thema

Programm

Short Talks 10Biofabrication / Artificial Vascular Structures

Termin

Chair

Thema

Programm

Short Talks 10
Biofabrication / Artificial Vascular Structures