Study On 3D Printed Gelatin/Sodium Alginate/Bioactive Glass Scaffold And Structural Bionics Optimization For Bone Defect Repair

The large bone defect,which is caused by trauma,tumor or infection,is a huge challenge in current clinical treatment.In general,bone transplantation methods such as autogenous bone transplantation,allogeneic bone transplantation and artificial bone transplantation are usually adopted in clinical surgery.However,the source of autologous bone is limited,allograft bone has the risk of infection,and artificial bone lacks osteoinductive activity.These shortcomings limit their clinical application.Therefore,in the field of orthopaedic repair,the study of new regenerated bone defect repairing materials with high biological activity and efficient function on promoting bone formation has become a challenge and hotspot in recent years,which will own huge clinical needs and market prospects.Bone tissue engineering has been proved to be an effective method for repairing bone defects.As an important bone tissue repairing material,bioactive glass(BG)has a good effect on promoting mineralization,bone formation and blood vessel formation of stem cells with the releasing of silicon and calcium ions.The gelatin/sodium alginate hydrogel is a mixture of natural polymer materials,which has good biocompatibility,tissue absorbability,low immunogenicity,especially excellent constructure with inorganic powder by 3D printing technology.But it has a poor compressive strength.Optimizing the composition materials and construction of internal microstructures of scaffold are two effective ways to improve its mechanical properties,biological activity,and vascularization properties.Though 3D printing technology can effectively construct porous bioactive glass scaffolds with the control porosity,pore size and other parameters,there still exists some problems on scaffolds such as the insufficient mechanical strength and poor biological activity after sintering.In this study,we prepared bioactive glass by sol-gel method and combined low temperature three-dimensional fiber deposition technology to manufacture a kind of gelatin/alginate/bioactive glass composite scaffold and core-shell scaffolds from the point of bionics.We studied the effects of post-treatment conditions,material composition on the mechanical properties,degradation rate,mineralization,cell proliferation and differentiation of bone tissue engineering scaffolds.We designed a new type of bionic multi-level porous structure through mechanical optimization method,combined low temperature three-dimensional fiber deposition technology manufacturing a kind of scaffolds with core-shell structure and explored the optimal design parameters for scaffolds.Bioactive glass prepared by sol-gel method had an uniform size distribution,low degree of crystallinity,porous surface and excellent mineralization property after a heat treatment and ball-milling.The composite scaffolds treated with 1%GTA solution not only possesssd an excellent compressive strength,water absorption and cytocompatibility,but also a more stable morphology.In the gelatin/sodium alginate/ bioactive glass composite scaffold system,calcium ions released from the bioactive glass could partially crosslink with sodium alginate during the formulation of the printing ink,which facilitated the formation of porous three-dimensional scaffolds.The mechanical properties of scaffolds were enhanced with the addition of bioactive glass and reached 10 MPa when the adding content of bioactive glass was about 30%wt(30 BG).The surface of the composite scaffolds with bioactive glass was rough,and the mBMSCs cells had a better adhesion on them.When the adding content of bioactive glass was 10%wt(10BG),the promotion effect on cell proliferation was significantly greater than that of gelatin/alginate scaffold.And when the adding content of bioactive glass was more than 10%wt,pH of scaffolds and culture medium was increased caused by the dissolution of calcium ions at the initial stage.PH in scaffolds and culture medium affected cells activity,and its promotion effect on cell proliferation(14 days ago)was inferior to the gelatin/sodium alginate scaffolds.But the effect on promoting cell proliferation in the later stage(after 14 days)gradually caught up with the gelatin/sodium alginate scaffold as ion release decreased.Scaffolds with bioactive glass showed a superior osteogenic differentiation ability and mineralization ability.A novel bionic scaffold with core-shell structure prepared by three-dimensional fiber deposition technology has high mechanical properties and high porosity through mechanical optimization design.We all know that the greater the porosity of scaffolds is,the more beneficial it is to the circulation of nutrients and waste.Porosity plays a crucial role in tissue repair and reconstruction.The design and preparation of scaffolds with core-shell structure provide us with a basis for further study of the influence on cell behavior and animal experiments,and provide us a new idea for the development of regenerative repair materials with high repair activity and excellent mechanical properties.