Control of cross-linking density in bioinks and integration of nanotechnology
June 5-9, 2017
Biofabrication is a new field of research where cells are fabricated together with materials in automated processes to 3D constructs with stratified organization . Lately, the need for a broader variety of bioinks has generated considerable research interest . We have in this context explored physically cross-linked hydrogels  as well as thiol-ene clickable artificial systems based on polyglycidols . In order to transfer this to more biologically active bioinks, we have recently prepared and thoroughly characterized thiol-ene clickable gelatin (GelAGE) as bioink. The first part of the lecture will thus compare standard methacrylated gelatin (GelMA) with GelAGE especiall with regards to the formation of high molecular weight polyacrylates in the case of GelMA. Moreover, we show that the controlled network formation of GelAGE enables the system to serve as a platform bioink for several Biofabrication technologies, and we demonstrate this at the examples of extrusion printing and digital light processing. Aside the pure printability, a control of drug loading and release into bioinks is of interest in order to accelerate tissue maturation or for drug testing. This may be achieved by supplementation of bioinks with nanoparticles. Mesoporous silica nanoparticles (MSN) for example can be loaded with drugs and designed to only release their payload after cell internalization . The second part of the talk will concern MSN with diameters of 350 nm as well as gold nanoparticles with a diameter of 30 nm as model systems. Both particle types were prepared with either positive or negative surface charge and formulated into a thiol-ene clickable bioink comprising negatively charged Hyaluronic acid . Rheological experiments show that both particle types can be supplemented in concentrations up to 10 mg/mL without affecting printability. Our data quantitatively shows that electrostatic interactions can be used to control the migration and release behavior of nanoparticles in and from printed hydrogels, and the subsequent uptake by cells. These results display a promising approach towards the local and temporal control of drug vectors in Biofabrication through a combination of bioink development with nanotechnology using a generic principle. References: 1. Groll J, et al. Biofabrication 2016;8: 013001. 2. Jungst T, et al. Chem. Rev. 2016;116:1496–1539 3. Schacht K, et al. Angew. Chem. Int. Ed. 2015;54:2816–2820. 4. Stichler S, et al. Ann. Biomed. Eng. 2017;45:273-285. 5. Bocking D, et al. Nanoscale 2014;6:1490-1498. 6. Jungst, T, et al. Angew. Chem. Int. Ed. 2017, DOI: 10.1002/anie.201700153.
Jürgen Groll, "Control of cross-linking density in bioinks and integration of nanotechnology" in "Biofabrication for Hierarchical in Vitro Tissue Models", Jürgen Groll (University of Würzburg, Germany) Jos Malda (University Medical Centre Utrecht, The Netherlands) Eds, ECI Symposium Series, (2017). http://dc.engconfintl.org/biofab_tissue_model/20