Three-dimensional Printing And Biological Properties Of Functional Bioactive Composite Scaffolds

Bone tissue engineering has changed the traditional treatment modes and provide a new approach for clinic treatment of bone defect.Among the basic components of seed cells,scaffolds and growth factors,scaffolds are the key factor that create bone tissue engineering system and determine the treatment effect.In this thesis,we successfully fabricated calcium sulfate hydrate/mesoporous bioactive glass(CSH/MBG)scaffolds,tricalcium silicate/mesoporous bioactive glass(C3S/MBG)cement scaffolds,Fe-MCS/PHBHHx scaffolds and BG@PDA-DFO ceramic scaffolds using 3D printing technique.The physiochemical properties,apatite mineralization ability and biological properties of those four kinds of scaffolds were systematically investigated.(1)CSH/MBG scaffolds were successfully fabricated by 3D printing,and they had a regular and uniform square macroporous structure,high porosity and excellent apatite mineralization ability.Human bone marrow-derived mesenchymal stem cells(hBMSCs)were cultured on scaffolds to evaluate the hBMSCs attachment,proliferation and osteogenesis-related gene expression.Critical-sized rat calvarial defects were applied to investigate the effect of CSH/MBG scaffolds on bone regeneration in vivo.The in vitro results showed that CSH/MBG scaffolds stimulated the adhesion,proliferation,alkaline phosphatase(ALP)activity and osteogenesis-related gene expression of hBMSCs.In vivo results showed that CSH/MBG scaffolds could significantly enhance new bone formation in calvarial defects compared to CSH scaffolds.(2)C3S/MBG cement scaffolds were successfully fabricated for the first time by 3D printing with a curing process,which combined the hydraulicity of C3 S with the excellent biological property of MBG together.The C3S/MBG scaffolds exhibited 3D interconnected macropores(~400 μm),high porosity(~70%),enhanced mechanical strength(>12 MPa)and excellent apatite mineralization ability.hBMSCs were cultured on the scaffolds to evaluate their cell responses,and the results showed that C3S/MBG scaffolds could stimulate hBMSCs attachment,proliferation and differentiation with increasing MBG component.The critical-sized rat calvarical defects as an animal model,in vivo results indicated both C3 S and C3S/MBG30 scaffolds could induce new bone formation,but the C3S/MBG30 scaffolds significantly improved osteogenic capacity compared to the pure C3 S scaffolds.(3)Mesoporous calcium-sillicate powders with different Fe incorporations(Fe-MCS)were synthesized by a sol-gel method.All of Fe-MCS powders exhibited orderd mesoporous channels and large BET surface areas.Fe-MCS/PHBHHx scaffolds were successfully fabricated by 3D printing,which showed 3D interconnected macropores(~350 μm),high porosity(~70%),proper mechanical strength(~5 MPa)and excellent apatite mineralization ability.hBMSCs were cultured on the scaffolds to evaluate their cell responses,and the results showed that 5Fe-MCS/PHBHHx scaffolds could stimulate hBMSCs attachment,proliferation and differentiation.However,the hBMSCs proliferation and differentiation on scaffolds were inhibited with increasing Fe incorporation(10Fe-MCS and 15Fe-MCS).(4)Amorphous BG powders were synthesized by an evaporation-induced self-assembly(EISA)process.3D porous BG ceramic scaffolds were fabricated by a 3D printing technique with a sintering process.Subsquently,deferoxamine(DFO)was decorated on BG ceramic scaffolds via polydopamine(PDA)coating to enhance osteogenesis and angiogenesis.BG@PDA-DFO scaffolds exhibited 3D interconnected macropores(~350 μm)and proper mechanical strength(~12 MPa).PDA coating could improve the apatite mineralization ability on BG ceramic scaffolds.hBMSCs were cultured on the scaffolds to evaluate their cell responses,and the results showed that BG@PDA-DFO scaffolds could stimulate hBMSCs attachment,proliferation and differentiation with increasing DFO content.In summary,four kinds of porous scaffolds have been successfully fabricated by 3D printing.CSH/MBG and C3S/MBG scaffolds combined the cement chemistry with the excellent bioactivity of MBG together,resulting in good bone-forming bioactivity,enhanced mechanical strength and biological properties.3D porous Fe-MCS/PHBHHx scaffolds showed good mechanical strength and bioactivity,and the scaffolds with less Fe incorporation could stimulate hBMSCs attachment,proliferation and differentiation.BG@PDA-DFO scaffolds had 3D interconnected macropores(~350 μm)and proper mechanical strength(~12 MPa),and could promote hBMSCs attachment,proliferation and differentiation with increasing DFO content.