3D Printing of a Self-Healing, Bioactive, and Dual-Cross-Linked Polysaccharide-Based Composite Hydrogel as a Scaffold for Bone Tissue Engineering.

Although 3D printing is becoming a dominant technique for scaffold preparation in bone tissue engineering (TE), developing hydrogel-based ink compositions with bioactive and self-healing properties remains a challenge. This research focuses on developing a bone scaffold based on a composite hydrogel, which maintains its self-healing properties after incorporating bioactive glass and is 3D-printable. The plain hydrogel ink was synthesized using natural polymers of 1 wt % N-carboxyethyl chitosan, 2 wt % hyaluronic acid aldehyde, 0.3 wt % adipic acid hydrazide, and alginate (ALG) (2, 5, and 10 wt %). Bioactive glass (BG) (0 and 5 w/v %) particles were incorporated into the plain matrix to obtain an osteogenic composite hydrogel. The material was characterized via rheology, field emission scanning electron microscopy/energy-dispersive X-ray spectroscopy (FESEM/EDS), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), swelling, degradation, bioactivity, and in vitro cellular assessments. Rheological evaluations confirmed that the specimen with 0 w/v % BG and 5 wt % ALG exhibited the highest ', ″, and viscosity values. All specimens exhibited self-healing, provided by two reversible dynamic bonds, namely, imine and acylhydrazone. Bioactivity evaluation by SBF immersion revealed the formation of HA particles on the composite hydrogels. MTT cytotoxicity assay on MG63 indicated that the composite sample containing 5 w/v % BG and 10 wt % ALG had the highest cell viability (95 ± 1.02%) by culture day 3. The developed approach presents a promising hydrogel ink formulation with a high potential for extrusion-based 3D printing of bone TE constructs.