Magneto-Enzymatic Microgels for Precise Hydrogel Sculpturing

abstract

The inclusion of hollow channels in tissue-engineered hydrogels is crucial for mimicking the natural physiological conditions and facilitating the delivery of nutrients and oxygen to cells. Although bio-fabrication techniques provide diverse strategies to create these channels, many require sophisticated equipment and time-consuming protocols. Herein, collagenase, a degrading agent for methacrylated gelatin hydrogels, and magnetic nanoparticles (MNPs) are combined and processed into enzymatically active spherical structures using a straightforward oil bath emulsion methodology. The generated microgels are then used to microfabricate channels within biomimetic hydrogels via a novel sculpturing approach that relied on the precise coupling of protein-enzyme pairs (for controlled local degradation) and magnetic actuation (for directional control). Results show that the sculpting velocity can be tailored by adjusting the magnetic field intensity or concentration of MNPs within the microgels. Additionally, varying the magnetic field position or microgel size generated diverse trajectories and channels of different widths. This innovative technology improves the viability of encapsulated cells through enhanced medium transport, outperforming non-sculpted hydrogels and offering new perspectives for hydrogel vascularization and drug/biomolecule administration. Ultimately, this novel concept can help design fully controlled channels in hydrogels or soft materials, even those with complex tortuosity, in a single wireless top-down biocompatible step. Magneto-enzymatic microgels, consisting of collagenase and magnetic nanoparticles, are used to sculpt internal channels within biomimetic hydrogels through the synergy of enzymatic degradation and remote magnetic guidance. This approach enhances cell viability by optimizing nutrient and oxygen distribution beyond conventional methods. Wireless control enables intricate hydrogel topographies, advancing vascularization and targeted drug delivery, marking a notable achievement in biofabrication. image

subject category

Chemistry; Science & Technology - Other Topics; Materials Science; Physics

authors

Mendes, MC; Pereira, JA; Silva, AS; Mano, JF

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

Unlocking the scientific excellence and innovation capacity of the University of Aveiro in supramolecular multicomponent biomaterials for enabling advanced biomaterials for healthcare (SUPRALIFE)

acknowledgements

This work was developed within the scope of projects of the CICECO-Aveiro Institute of Materials, UIDB/50011/2020 (DOI 10.54499/UIDB/50011/2020), UIDP/50011/2020 (DOI 10.54499/UIDP/50011/2020), and LA/P/0006/2020 (DOI 10.54499/LA/P/0006/2020), financed by national funds through the FCT/MEC (PIDDAC). The authors would also like to acknowledge funding from the European Research Council (ERC) through the project "Reborn" (ERC-2019-ADG-883370) and funding from the European Union's Horizon Europe research and innovation programme under Grant Agreement No. 101079482 ("SUPRALIFE"). Additionally, the appreciation to the FCT doctoral grant SFRH/BD/146740/2019 (awarded to Maria C. Mendes) was extended, the FCT doctoral grant 2022.13351.BD (awarded to Joao A. Pereira) and individual contract 2021.02196. CEECIND (DOI 10.54499/2021.02196.CEECIND/CP1659/CT0002) (awarded to A. Sofia Silva).