Biomimetic gelatin/HA biocomposites with effective elastic properties and 3D-structural flexibility using a 3D-printing process

A printing process can enable the flexible and complex design of tissue-specific three-dimensional (3D) micro/macroscale structures. Composite scaffolds printed using bioceramics and various synthetic polymers or natural hydrogels have been previously employed in bone tissue regeneration because of their properties which can compensate for the shortcomings of either ceramic or hydrogel. In particular, the combination of gelatin and hydroxyapatite (HA) fabricated using electrospinning and leaching methods have been applied in bone tissue regeneration due to various mechanical and biological synergistic effects of the composites. However, 3D-printing of the biomimetic composite bioink (gelatin and high weight fraction of bioceramic, similar to 70 wt%) has been very difficult due to the rheological properties of gelatin which makes them very sensitive to processing conditions, and because of the high wt% of HA in the bioink, HA can be easily sedimented during a printing process, resulting in poor extrusion-ability due to the clogging phenomenon in the nozzle. To solve the problem, in this study, we propose a new type of bioink in which a polyol was employed as a biocompatible processing agent. Various material/processing factors were considered to develop an optimal condition to obtain stable macroscale and mesh-structured gelatin/HA composites. The biocomposites showed outstanding hyperelastic recoverable properties compared to the alginate/HA composite with similar geometrical structure. Using in vitro human adipose stem cells, we observed that the biocomposite performed as a well-organized cell-activating platform for encouraging efficient cellular activities. The proposed bioink formulation and printing process showed great potential for successfully and stably fabricating a biomimetic organic/inorganic composite for hard tissue engineering.