Study On Improvement Of Basic Performaces,Osteogenesis And Degradability Of Calcium Phosphate Cement By Adjusting Calcium Content And Incorporation Of Zn-Doped Calcium Silicate And Dopamine-Modified PLGA Microspheres

Calcium phosphate cement?CPC?has been widely used in the field of bone repair due to its good injectability,moldability,in-situ self-setting ability biocompatibility,and osteoconductivity.CPC also has poor mechanical strength,slow degradation rate,and unsatisfactory osteoinductivlity.In this study,the mechanical,degradable,and osteogenic capability of CPC were improved by regulating the calcium content of solid phases,incorporating zinc-doped calcium silicate compresing teo functional ions and adding dopamine-modified poly?lactic-co-glycolic acid??PLGA?microspheres,respectively.The physicochemical and cytological properties of these modified CPCs were systematically investigated.In this study,the improvement of CPC bone repair material of partial crystalline calcium phosphate-calcium hydrogen phosphate?PCCP-DCPA?system,which was developed by our research group,was used as the research subject.The basic performances were further optimized by studying the influence of the calcium content on CPC performances via regulation of the calcium content of PCCP.The research results show that compared to the original CPC,the increase of the calcium content by 2%and 5%reduced the porosity of the hydrated cements,and raised the crystallinity and compressive strength of the hydrated CPC,as well as promoted the adhesion,viability,and m RNA expression of osteogenesis-related genes of mouse bone marrow mesenchymal stem cells?m BMSCs?.However,as the increased content of calcium reached 10%,the negative effects on the performances of CPC occurred.Given that CPC lacks osteoinductivity,we prepared zinc-doped calcium silicate?Zn-CS?powders with different amount were prepared by a chemical precipitation method.Here,Zn²⁺was introduced into the CPC matrix in the form of Zn-CS and the release behavior of which could be controlled by the doping amount of zinc,accompanied by the sustained and steady osteogenesis/angiogenesis-related gene expression showed that the additive amount of calcium metasilicate?CS?in CPC was optimized as 10 wt%by high-throughput screening.On the basis of the optimal amount of CS,the osteoinductivity of CS-CPC was further improved mol%,were also determined by the high-throughput screening method.The addition of Zn-CS reduced the porosity and increased the crystallinity of the hydrated cement matrix,thereby significantly improving the compressive strength of CPC.The addition of Zn-CS also promoted the adhesion and viability of m BMSCs on the cement surface.Incorporation of PLGA microspheres is an effective method to promote degradation of CPC,which can accelerate bone formation.However,due to its poor hydrophilicity and bioactivity,addition of PLGA will lead to unsatisfactory binding to CPC matrix and reduce the bioactivity of CPC.We prepared the dopamine-modified PLGA?DA-PLGA?microspheres were prepared by coating the surface of PLGA microspheres with DA molecules.The modified microspheres were further added into the CPC matrix to obtain a DA-PLGA/CPC composite.The hydrophilicity of DA-PLGA microspheres was significantly improved owing to the formation of hydrophilic polydopamine membrane on the surface compared with that of pure PLGA microspheres,which increased the dispersity of the microspheres in the cement matrix,enhanced the microsphere-matrix interfacial bonding strength,and thus significantly raising the compressive strength of CPC.The presence of polydopamine membrane also slowed down the early burst release of acidic degradation products of PLGA,which effectively reduced the risk of aseptic inflammation.Compared with the control,DA-PLGA/CPC significantly up-regulated the m RNA expression levels of cell adhesion-related markers.The composite comprising 10 wt%DA-PLGA microspheres notably enhanced the ALP activity and the expression levels of osteogenesis-related genes of m BMSCs.