Application Of 3D Printing Technology In Bone And Cartilage Tissue Engineering

3D printing technology has been widely used in the repeatable manufacture of complex geometric objects in the fields of art,engineering,architecture and so on.In recent years,it has been employed in the field of regenerative medicine and tissue engineering,including the regeneration of skin,heart,liver,bone,cartilage,muscle,and other tissues.It is apporiate for the application of 3D printing in the bone and cartilage tissue engineering because of the unique physical structure and the microenvironment.In order to achieve the better treatment effects,researchers have focused on the influence of structure design,bio-inks and 3D printing technology in bone and cartilage tissue engineering.However,these studies often concentrate on one of these aspects,and there are few studies involving the whole process of 3D printing,which makes a big obstacle for ultilization of this technology in the treatment of clinical diseases.Therefore,this paper explored each step of 3D printing technology in bone and cartilage tissue engineering.Firstly,the role of 3D printed porous structure constructed by implicit function in bone repairring and cartilage protection was evaluated.Subsequently,biomaterials which can be used for 3D printing and restoring bone and cartilage tissues were designed.Finally,the bone and cartilage injuries in the animal model were repaired by in situ 3D printing technology with the assistance of multi-degree-of-freedom robots.The main work and research results of this paper are as follows:(1)The application of 3D printed TPMS porous scaffold in bone and cartilage tissue engineering was studied,including the structural design of TPMS porous structure,finite element simulation,3D printing,surface morphology and mechanical properties test.The Young's modulus of these porous scaffolds constructed by TPMS method can be reduced to less than 10 GPa,and the porosity can be close to 50%,which were close to the mechanical parameters of cortical bone.After 5 weeks'implantation,outstanding osseointegration can be observed,and a large number of new bone tissue can be found in the pores of the scaffolds.Then the porous meniscus prosthesis with porosity of about 40%was designed by TPMS method,and the load in the joint cavity was calculated by finite element simulation.This structure can reduce the peak shear stress and compressive stress on the cartilage surface,and the stress concentration area was also reduced.In the 12-weeks'animal experiment,the surface of knee cartilage receiving porous meniscus prosthesis was significantly better than that of the control group.(2)We designed the interpenetrating network bioink based on sodium alginate-polyvinyl alcohol and the double network bioink based on polypeptide-acrylamide-hyaluronic acid,which were used in bone and cartilage tissue engineering,respectively.Sodium alginate-polyvinyl alcohol bioink can be quickly gelled within 10 seconds under UV irradiation,and the Young's modulus can reach 6 MPa after freeze-thaw reaction.Polypeptide-acrylamide-hyaluronic acid bioink shown good toughness and compression resistance,the compression limit can exceed70%,and the compression modulus can exceed 200 KPa.These two kinds of bioink have good biocompatibility and shaping ability,and can promote the regeneration of bone and cartilage in animal models.(3)The in vitro bone and cartilage damages were repaired in situ by 3D scanning and 3D printing techniques.The errors of the in situ 3D bioprinting in the three models were less than0.5mm according to the results of 3D model comparison,which can fully meet the clinical requirements.Then the four-degree-of-freedom and six-degree-of-freedom robots were introduced in the study,and the laser calibration technology was used to compensate the error.The bone defects were repaired by in situ 3D printing in a large animal model.The defect area with a volume of 1570 mm~3 could be repaired within 12 minutes,and the regeneration rate reached 70%after 12 weeks.The cartilage defect was repaired by in situ 3D printing in a small animal model.The cartilage defect with a volume of 78 mm~3 could be repaired within 90seconds.After 12 weeks,the repair effect was similar to that of scaffold implantation group.