Overview of the novel microfluidic-assisted fabrication method to create beaded GelMA whereby (a) GelMA passes through an inlet between oil/ surfactant pinching flows to form microbeads, which are physically crosslinked in cold water, purified, and further chemically crosslinked and annealed using light. (b) The flow-focussing device connected to a reservoir for GelMA beads storage. (c) Range of bead sizes achievable by altering fabrication parameters.
Overview of the novel microfluidic-assisted fabrication method to create beaded GelMA whereby (a) GelMA passes through an inlet between oil/ surfactant pinching flows to form microbeads, which are physically crosslinked in cold water, purified, and further chemically crosslinked and annealed using light. (b) The flow-focussing device connected to a reservoir for GelMA beads storage. (c) Range of bead sizes achievable by altering fabrication parameters.

Gelatin methacryloyl (GelMA) is a highly promising biomaterial candidate for a range of tissue engineering and regenerative medicine applications. GelMA exhibits similarities in structure and biochemical composition to native extracellular matrix (ECM) in tissues, and its biocompatibility, thermo-sensitivity, tissue adhesiveness, and tuneable stiffness contribute to its popularity for 3D tissue culture.

In a new article published in Biomaterials, Sheikhi and colleagues from the University of California - Los Angeles propose a novel micromanufacturing method to produce injectable microporous GelMA made up of annealable microbeads, which have improved biological properties compared to bulk GelMA [Sheikhi et al. Biomaterials (2018) doi: 10.1016/j.biomaterials.2018.10.040].

Sheikhi and colleagues present a thorough characterisation of the system parameters influencing GelMA bead formation within the microfluidic device and their post-processing alongside comparison of the mechanical and rheological properties of the individual and annealed GelMA beads compared to the bulk material. Notably, the authors address the challenge of maintaining high cell viability inside GelMA hydrogels with high polymer concentrations required for shape fidelity for self-standing tissue constructs via 3D cell culture of NIH/3T3 fibroblasts. After 14 days, 100% cell survival was observed with 20% w/v GelMA microbead scaffolds compared to bulk GelMA in which the cells did not survive at such high polymer concentrations.

“When GelMA concentration increases, the pore size of bulk hydrogel decreases. Moreover, bulk GelMA does not have interconnected pores. Therefore, the shortage of space as well as hindered nutrient and oxygen diffusion in bulk GelMA result in cell death. The annealed beaded GelMA provides large, interconnected pores and supports cell functions,”explains first-author Dr Amir Sheikhi from the University of California – Los Angeles.

The authors also highlight that this breakthrough fabrication method is suitably versatile to translate other bulk polymeric materials into annealable hydrogel beads, promising the ability to independently tune the microporosity of 3D hydrogel constructs and stiffness.