3D printed cellulose nanofiber-reinforced and iron-crosslinked double network hydrogel composites for tissue engineering applications: Mechanical properties and cellular viability

Abstract

Additive manufacturing (i.e. 3D printing) is a promising technology for creating three-dimensional (3D) complex tissue-engineered hydrogel structures based on computer digital models resulting from patient-specific anatomical data of the organs. However, besides the printing process, it is worth studying the variation of individual components of the developed hydrogel composites to enable their suitability for tissue engineering. In this work, we shaped 3D printed multi-layered dual (UV- and Fe³⁺ ions)-crosslinked structures using hydrogel-inks composed of polyacrylamide (PAM), alginate (ALG), and cellulose nanofibres (CNFs). For extrusion, ALG in hydrogel precursor ink acted as a viscosity modifier owing to rapid gelation in the presence of low Ca²⁺ ions and CNF provided shear-thinning behavior. With the addition of optimal content of CNF (3 wt%), the mechanical properties of 3D printed composite hydrogel were enhanced and tuned using different fiber orientations. The maximum tensile stress of PAM/ALG_1.5/3CNF composite hydrogel is measured as ∼162 kPa, and maximum tensile toughness as ∼54 kJ/m³ supporting a good fracture resistance. Moreover, CNF-Fe³⁺ loaded 3D printed dual-networked composite hydrogels could disperse energy more efficiently and displayed maximum tensile stress as ∼285 kPa and maximum toughness as ∼200 kJ/m³. Further, In the current study, developed composite structures exhibited enhanced swelling ratio and thermal stability. In addition, finite element (FE) modelling was also exploited to analyze the novel anisotropic composite structures using efficient computational techniques. It is established that varying nanofiber content and fibrils orientation can be utilized to modulate the physicochemical, mechanical, and biological characteristics of printed structures. Overall, PAM/ALG_1.5/3CNF-Fe³⁺ printed composite structures present substantial stretchability, enhanced anisotropic mechanical and physicochemical properties with excellent cytocompatibility.