3D Printing Porous Bio-ceramic Scaffolds Assemble Controlled Drug Release Microspheres And Cell Compatibility Investigation

The statement and development of bone tissue engineering have provided a new treatment for bone defects.Tissue engineering scaffolds should have enough nutrients,growth factors,anti-inflammatory and anticancer properties for new tissue ingrowth.Hence,it is very important for clinical treatment that scaffolds could be endowed with controlled release of drugs,nutrients and growth factors.In this study,porous calcium silicate/tricalcium phosphate(CS/?-TCP)bioactive ceramic scaffolds were fabricated via three-dimensional printing technology and the scaffolds exhibit a uniform pore size distribution and high pore connectivity.The effects of CS content on the physicochemical properties,in vitro bioactive,degradation and cytocompatibility properties were systematically investigated.The results showed that the addition of CS could inhibit the growth of crystal during sintering process of scaffolds.With the increasement of CS content,the amount of porosity on the scaffold surface enlarged,and the apatite-forming ability was similar trend.However,shrinkage and compressive strength of scaffolds decreased with the amount of CS increase.The cell viability test results demonstrated 45 wt.% CS scaffold had a significant inhibitory effect on cell proliferation compared to the ?-TCP scaffold after being cultured for 1,4 and 7 days.The reason for this result was that excessive ion dissolution rate of the scaffold increased pH value of cell-culture medium,reducing the cell proliferation behavior.However,the scaffolds with CS content less than 15 wt.% had no negative effect and could promote the osteogenic differentiation of murine bone marrow stem cells(mBMSCs).Hollow mesoporous bioactive glass microspheres(HMBGMs)with controlled shell thickness were fabricated via a hydrothermal-assisted self-transformation method employing cetyltrimethyl ammonium bromide(CTAB)as a mesoporous template.The effect of some factors,such as addition content of CTAB,ammonia concentration,hydrothermal time and temperature on the morphology,structure and cavity radius of the microspheres were investigated.Via controlling those technological parameters,the morphology and structure of HMBGMs could be regulated.The in vitro bioactivity test results indicated that HMBGMs showed excellent apatite-mineralization ability.The cell experiments showed that the HMBGMs concentration less than 500 ?g mL-1 could stimulate the proliferation of the mBMSCs.To investigate the capability of HMBGMs as drug carriers,Alendronate(AL)was introduced into the pores of HMBGMs.The results showed that HMBGMs exhibited a high drug loading efficiency(40.47%)and the 14-day accumulative release total was 88%.Compared with HMBGM-AL system,the formula optimization of HMBGM-AL by gelatin cover showed a significantly controlled release effect.The AL cumulative release for 14 days decreased from 88% to 68%.This excellent drug release property of HMBGM-AL was further demonstrated by the cell viability test.The cell differentiation assays indicated that HMBGM-AL system could delay osteogenic differentiation of mBMSCs.Drug-loaded microspheres/scaffolds controlled release system was fabricated by gelatin treatment method.The effect of HMBGM-AL in the scaffolds on cell adhesion,proliferation and differentiation was investigated.The study suggested that 15%CS-HMBGM group could significantly stimulate the proliferation of the mBMSCs compared with 15%CS scaffold.Moreover,15%CS-HMBGM and 15%CS-HMBGM-AL groups can dramatically up-regulate bone-related genes compared with 15%CS scaffold for 14 days,especially in 15%CS-HMBGM-AL group.