Porous granular hydrogel scaffolds biofabricated from dual-crosslinked hydrogel microparticles for breast tissue engineering

Hydrogel scaffolds play a crucial role in tissue engineering; however, traditional bulk hydrogel scaffolds (BHS) often suffer from insufficiently sized pores (nanoscales), impeding cellular infiltration, development, and expansion. This limitation affects oxygen and nutrient exchange efficiency, in which case it relies extensively on liquid permeation and bulk hydrogels swelling. In contrast, hydrogel microparticles (HMPs) have proven to be both printable and injectable, allowing the development of modular thick constructs with interconnected pores. This study introduces a novel method of fabricating porous granular hydrogel scaffolds (GHS) by printing thermo-crosslinked gelatin methacryloyl (GelMA) HMPs granular hydrogels before chemical crosslinking (dual-crosslinking). The scaffolds exhibit an average pore fraction ranging from 14 % to 23 % and an average pore size varying from 4923 μm(2) to 8185 μm(2) (with equivalent circular diameter of 80-102 μm). In vitro experiments demonstrated the effective infiltration, adhesion, proliferation, and adipogenic differentiation of human adipose-derived stem cells (hADSCs) within the scaffold pores. Additionally, in vivo observations confirmed the presence of differentiated adipose cells within the central pores after 4 weeks. These results collectively suggest the proposed microspheres printing technique holds significant promise for fabricating microporous scaffolds and further applications in tissue engineering.