Oxidized nanocrystalline cellulose–alginate filaments as pH-responsive bioink for 3D and 4D bioprinting

3D/4D bioprinting has become a powerful strategy in tissue engineering, regenerative medicine, and drug delivery. Among printable biomaterials, pH-responsive hydrogels are particularly attractive for applications in acidic environments such as the stomach or tumor microenvironments. In this study, composite hydrogel filaments were fabricated using alginate and nanocrystalline cellulose (NCC), with cellulose concentrations ranging from 0% to 9%. NCC was further modified by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation to produce oxidized-NCC (ONCC) to introduce pH sensitivity. The water uptake of the filaments ranged from 0.7% to 2.5%, depending on cellulose content. Dimensional stability, evaluated by reductions in width, length, and aspect ratio under neutral (pH 7) and acidic (pH 2) conditions, revealed that ONCC-containing filaments underwent significantly greater contraction than NCC-containing filaments, with up to ∼30% width reduction and ∼10% aspect ratio reduction in acidic medium. These findings demonstrate that TEMPO-mediated oxidation imparts pH responsiveness to cellulose, enabling the development of alginate/ONCC composites as promising biomaterials for 3D/4D bioprinting with potential applications in drug delivery and regenerative medicine.