Three dimensional cell printing with sulfated alginate for improved bone morphogenetic protein-2 delivery and osteogenesis in bone tissue engineering.

Three-dimensional (3D) cell printing is a unique technique that enables free-form fabrication of cell-laden hydrogel scaffolds with controllable features and interconnected pores for tissue engineering applications. To this end, bioink materials able to offer good printability and favorable cellular interaction are highly required. Herein, we synthesized alginate sulfate, which is a structural mimic of heparin that can strongly bind with growth factors to prolong their activities, and studied its feasibility for cell printing applications. Several bio-inks composed of alginate and alginate-sulfate were studied to characterize their material properties and their utilities in 3D printing. The inclusion of alginate-sulfate in bio-inks (alginate/alginate-sulfate) did not significantly influence their rheological properties and allowed for a good 3D printing processibility with distinct pores and features. Moreover, alginate/alginate-sulfate bio-inks exhibited an improved retention of bone morphogenetic protein 2 in 3D-printed scaffolds. Osteoblastic proliferation and differentiation in vitro were promoted by alginate/alginate-sulfate 3D-printed constructs with an optimal composition of 3% alginate and 2% alginate-sulfate. We envision that bio-inks displaying prolonged interactions with growth factors will be useful for tissue engineering applications including bone regeneration.