M.Sc.

Nießing, Bastian

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  • Publication
    High-Speed-Microscopy for Scalable Quality Control in Automated Production of Stem Cell Spheroids for Tissue Engineering
    ( 2023)
    Krieger, Judith
    ;
    Nießing, Bastian
    ;
    König, Niels orcid-logo
    ;
    Schmitt, Robert
    The EU Horizon 2020 project »JointPromise« implies the conception and implementation of an end-to-end automated production platform for three-dimensional joint implants, paving the way for tissue-engineered implants able to regenerate deep osteochondral defects. Spheroid-based implants provide a novel approach in tissue engineering by aggregating progenitor cells into potent microtissues. After the differentiation of cartilaginous microtissues, functional joint implants are assembled via 3D bioprinting to match the complex structural organization of native cartilage tissue. As the automation approach of the project aims to overcome bottlenecks in manual production such as product variability, lack of scalability and high personnel costs, a high-throughput quality control system is crucial for the production of reliable Advanced Therapy Medicinal Products (ATMPs). By establishing not only a technical solution for the full digitization of the cell culture plates but also an intelligent image processing algorithm for the detection of the cell spheroids, relevant process parameters like size distribution and growth curves can be detected. Critical thresholds in spheroid growth are evaluated to minimize risks of carcinogenic tissue formation in vivo as well as to define harvest criteria to prevent inhomogeneous bioprinting results. In order to calculate the required throughput and elaborate optimization potentials of the automated spheroid production, voids in the cultivation vessel or disrupted aggregates due to media changes or transportation are detected. Ultimately, the high-speed-microscopy complies with the requirements of a high-throughput automated cell production platform to meet the rising demand for alternative therapeutic approaches in regenerative medicine.
  • Publication
    Automated Manufacturing of Microtissue Based Osteochondral Implants: The »JOINTPROMISE« Platform
    ( 2022)
    Krieger, Judith
    ;
    Nießing, Bastian
    ;
    König, Niels orcid-logo
    ;
    Luyten, Frank P.
    ;
    Papantoniou, Ioannis
    ;
    Schmitt, Robert H.
    Over 300 million cases of osteoarthritis were reported in 2017, stating one of the most prevalent chronic joint diseases worldwide characterized predominantly by long-term progressive cartilage and subchondral bone degeneration. Conventional therapy approaches utilize pharmacotherapy mostly for pain relief and at end stage disease treated by whole joint replacement surgery to retrieve some mobility and function. Novel Regenerative Medicine (RM) strategies employing Tissue Engineered implants could enable cure, more than care, of such life-constraining disabilities to meet the rising demand for medical interventions due to an ageing world population. Engineering joint tissue implants for the regeneration of the cartilage-bone unit of the joints remains a challenge due to the complex structural organization and functionality of native joint tissue. The use of microtissue/spheroid platforms has enabled differentiation and maturation of cartilage intermediates and gives hope for the engineering of efficient large-scale implants for osteochondral regeneration. However, there is still lack of enabling technologies for scaling of these approaches and robust manufacturing with end-to-end automation of such advanced therapeutic medicinal products (ATMPs). To allow sufficient scaling, overcome risks of contamination as well as inconsistent product quality in manual production procedures, the automated, GMP-compliant manufacturing platform »JointPromise« is developed. By establishing a robust, large-scale manufacturing process, a reliable microtissue-based product for the treatment of deep osteochondral defects can be generated with suitable productivity. The platform concept is based on the translation of Standard Operating Procedures (SOPs) for microtissue production, harvest and condensation into a sequence of automated process steps. Derived process design criteria and technical specifications result in device requirements for an automated production process. After initiating the conceptualizing stage of the platform design by creating a 2D layout according to the material flow of the translated SOPs, the final arrangement of devices was optimized in the overall 3D CAD model. The resulting production platform model combines all required devices for cell cultivation, microtissue harvest and ATMP production in an overall layout consisting of pipetting units, an incubator, centrifuge, bioprinter and housing for a defined hygienic environment. Following the SOPs, about 28,000 microtissue spheroids can be produced within 21 days of culture out of 1 mL cell suspension per tissue culture plate. To reach the required productivity of around 100 tissue culture plates per implant, the production platform will need to process around 70 L of liquids during seeding and harvest processes and 5 L per cell media change to produce around 2.8M microtissue spheroids in 21 days. The build-up of the »JointPromise« platform is followed by the implementation of the control software COPE (Control Operate Plan Execute, Fraunhofer IPT, Aachen, Germany) for process controlling and monitoring during cell seeding, cultivation and harvest.
  • Publication
    Implementation of an Automated Manufacturing Platform for Engineering of Functional Osteochondral Implants
    ( 2022)
    Krieger, Judith
    ;
    Nießing, Bastian
    ;
    König, Niels orcid-logo
    ;
    Mota, Carlos
    ;
    Pointe, Vanessa la
    ;
    Rijt, Sabine van
    ;
    Kondro, Douglas
    ;
    Hiatt, Michael
    ;
    Viellerobe, Bertrand
    ;
    Brisson, Bruno
    ;
    Marechal, Marina
    ;
    Geris, Liesbet
    ;
    Luyten, Frank P.
    ;
    Papantoniou, Ioannis
    ;
    Schmitt, Robert
    The EU Horizon 2020 project »JointPromise« proposes the development and implementation of an end-to-end automated production platform for three-dimensional joint implants, paving the way for tissue-engineered implants able to regenerate deep osteochondral defects. Currently, the manufacturing pipeline consists in manual production processes for microtissue cultivation, harvest and bioassembly into larger implants. In the conceptualizing stage of this project, the manual processes were translated into standard operating protocols (SOPs) and process design criteria like material flow and throughput as well as technical specifications of laboratory devices for an automated performance were elaborated. Spheroid-based implants provide a novel approach in tissue engineering by aggregating progenitor cells into potent microtissues. After the differentiation of cartilaginous microtissues, functional joint implants are assembled via 3D bioprinting to match the complex structural organization of native cartilage tissue. The »JointPromise« platform includes suitable devices for cell and microtissue cultivation, harvest and implant production as well as quality control in an overall layout consisting of according pipetting units, incubator, centrifuge, bioprinter and high-speed microscope. After initiating the platform build-up, a control software for process controlling and monitoring during cell seeding, cultivation and harvest is implemented. Clinical feasibility and efficacy of osteochondral defect regeneration by the produced joint implants will subsequently be proven in large animal models.