Multi-material 4D-printing of a Magneto-responsive Hydrogel Scaffold with Tuned Stiffness

Abstract

The physical, chemical, and biological versatility and high water content of hydrogels have been taken advantage of to fabricate hydrogels that mimic the extracellular matrix (ECM) structure of native tissues and applied in the field of cell and tissue engineering to provide the cells with a 3D scaffold structure. Especially in tissue engineering, the creation of a suitable hydrogel scaffold with hard and soft interfaces that is capable of both supporting cell growth and stimulation for guided differentiation for tissue interface studies is a primary concern for advancements in tissue engineering. The ideal scaffold with hard and soft interfaces can be achieved by finetuning its biological, biochemical, structural, and mechanical properties for optimal cell proliferation and differentiation.

In this thesis, a magneto-responsive hydrogel scaffold composed of gelatin (Gel, 2.5%), alginate (Alg, 5%), and iron oxide microparticles (10% w/v) was developed and mechanically and rheologically characterized before, during and after the application of a uniaxial static magnetic field. The magneto-responsive hydrogel scaffolds were created through multi-material 3D printing using magnetic and non-magnetic hydrogel inks. The magnetic inks contained magnetic particle (MP) inclusions within its polymer network while the non-magnetic hydrogel ink had no MPs. The 3D printing process allowed for a local control in the magnetic and non-magnetic hydrogel distribution to create hard and soft hydrogel interfaces. The printability and shape fidelity of various ink compositions were evaluated, so that the final composition of Gel:Alg ratio of 1:2 (2.5%:5.0%) with 10% MP was chosen for further mechanical and rheological characterization. The magnetic hydrogel scaffold exhibited magnetorheological properties as it mainly increased the effective Young’s modulus, storage modulus, and damping factor, and decreased viscosity under a uniaxial static magnetic field application.

In tissue engineering, the developed hydrogel scaffold, which is locally responsive to magnetic cues, shows great potential for creating scaffolds capable of continuously stimulating embedded cells in a non-contact manner. As a proof of concept, a bi-layered, multi-material hydrogel scaffold was created with increased surface area attachment points between each hydrogel material to mimic the osteochondral tissue interface. The increased surface area between both layers was achieved through a checkered pattern design with alternating magnetic and non-magnetic hydrogel sections printed alongside each other.