PREPARATION AND APPLICATIONS OF 3D BIOPRINTING BIOINKS FOR REPAIR OF BONE DEFECTS, BASED ON CELLULOSE NANOFIBRILS HYDROGELS WITH NATURAL OR SYNTHETIC CALCIUM PHOSPHATE PARTICLES

摘要

The present invention relates to preparation of bioink composed of cellulose nanofibril hydrogel with native or synthetic Calcium containing particles. The concentration of the calcium containing particles can be between 1% and 40% w/v. Such bioink can be 3D Bioprinted with or without human or animal cells. Coaxial needle can be used where cellulose nanofibril hydrogel filled with Calcium particles can be used as shell and another hydrogel based bioink mixed with cells can be used as core or opposite. Such 3D Bioprinted constructs exhibit high porosity due to shear thinning properties of cellulose nanofibrils which provides excellent printing fidelity. They also have excellent mechanical properties and are easily handled as large constructs for patient-specific bone cavities which need to be repaired. The porosity promotes vascularization which is crucial for oxygen and nutrient supply. The porosity also makes it possible for further recruitment of cells which accelerate bone healing process. Calcium containing particles can be isolated from autologous bone, allogenic bone or xenogeneic bone but can be also isolated from minerals or be prepared by synthesis. Preferable Calcium containing particles consist of β-tricalcium phosphate which is resorbable or natural bone powder, preferably of human or porcine origin. The particles described in the present invention have particle size smaller than 400 microns, or more preferably smaller than 200 microns, to make it possible to handle in printing nozzle without clogging and to obtain a good resolution. Cellulose nanofibrils can be produced by bacteria orbe isolated from plants. They can be neutral, charged or oxidized to be biodegradable. The bioink can be additionally supplemented by other biopolymers which provide crosslinking. Such biopolymers can be alginates, chitosans, modified hyaluronic acid or modified collagen derived biopolymers.