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3D/4D microprinting of biomaterials

Mainik, Philipp

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Abstract

In the last few decades, 3D printing has emerged as a preferred alternative to conventional polymer manufacturing. This transformation has been driven by new key technologies for manufacturing as well as by the development of new materials for these arising technologies. Among those technologies, light-based 3D printing particularly stands out due to its capability to produce 3D objects fast and precisely. The rising interest and demand for new materials, i.e. photocurable inks, for specifically designed applications are driving forces for innovations in this field. This thesis focusses especially on the design of new biomaterial inks for 3D laser printing at the microscale and expanding their application in in vivo microprinting. The presented new biomaterials cover synthetic as well as natural-based systems and focus on implementing new material properties and functionalities. In detail, this includes the expansion of printable synthetic materials to very soft synthetic materials by introducing a new ink design for multiphoton 3D laser printing based on supramolecular interactions. This new synthetic ink design allows for 3D printing of very soft materials which are highly desired in bioapplications. In addition to addressing current limitations of synthetic biomaterial ink, a natural-based biomaterial ink based on collagen is presented. The microprinted collagen hydrogels exhibited cell-adhesive properties and were composed of a highly porous collagen network. After characterizing the static material properties, the printed collagen was studied for its temperature-responsive folding motif. The fully reversible shrinkage and recovery of printed collagen upon heating and cooling was attributed to the folding and unfolding of the collagen binding motif – experimentally as well as theoretically. The new responsive mechanism based on polypeptide folding or unfolding opens new opportunities to equip and use natural-based biomaterials with stimuli-responsive properties. Moving toward application, this thesis also covers the implementation of biomaterials in in vivo microprinting. For this purpose, a suitable synthetic biomaterial ink is chosen to meet several important criteria for multi-photon 3D laser printing directly in developing organisms of medaka fish and fruit flies. In this collaborative study, the effect of the ink microinjection, multiphoton 3D laser printing process, and printed material on the development of the organisms is studied and evaluated. The presented framework opens new opportunities for in vivo microfabrication paving the way towards printed microimplants and drug delivery devices.

Document type: Dissertation
Supervisor: Blasco, Prof. Dr. Eva
Place of Publication: Heidelberg
Date of thesis defense: 17 October 2025
Date Deposited: 08 Dec 2025 14:41
Date: 2025
Faculties / Institutes: Fakultät für Chemie und Geowissenschaften > Dekanat der Fakultät für Chemie und Geowissenschaften
DDC-classification: 540 Chemistry and allied sciences
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