Research On Preparation And Properties Of Sr²⁺ And Mn²⁺ Doped On β-TCP Porous Biomimetic Bone Bioceramics

The"14th Five-Year Plan"Special Plan for Sanitation and Health Science and Technology Innovation emphasises the need to develop novel surgical implant materials for the bone and joint motion system and bone/cartilage integrated regenerative repair materials.As we all known,bones play a vital role in preserving the normal physiological function of the human body with the capabilities of supporting organs and withstanding external forces.Bone defect is a prevalent clinical ailment and is commonly classified by predisposing causes including pathological processes and human factors.The presence of bone defects can result in bone disunion,delayed or non-healing,and local dysfunction,causing significant inconvenience in people’s daily lives and work.Implantation of bone repair material is the primary treatment methods for handling large segmental bone defects.Currently,natural bone repair materials and artificial bone repair biological materials are common clinical materials.However,natural bone repair materials can not satisfy the practical requirements due to limitations in donor availability,the need for additional surgery,and difficulties in controlling shapes.As a contrast,though artificial bone repair biological materials have merits of sufficient sources and simple manufacturing process,they still face challenges such as immune rejection and a lack of bone inductance.Hence,developing secure and novel materials for bone repair with regenerative capabilities has been regarded as a research hot.β-Tricalcium phosphate（β-TCP）bioceramics have become a popular material for bone repair due to their good biocompatibility,biodegradability,biomimetic mineralisation,bone conductivity,and non-toxic properties post-implantation.Nevertheless,the mechanical properties ofβ-TCP are relatively poor,exhibiting substantial brittleness and susceptibility to external impact.Besides,their capacity to stimulate osteogenesis is limited as well.In order to solve these issues,trace elements or a three-dimensional network of bone-like porous structures is frequently introduced into the system ofβ-TCP.Specically,strontium ion(Sr²⁺)and manganese ion(Mn²⁺)are crucial elements in the reconstruction and stabilization of bones and in the improvement of their mechanical and biological properties.Moreover,the three-dimensional network structure could support the growth of blood vessels,new bone tissue,and the transportation of nutrients.However,the current research mainly concentrates on the effect of metal ion modification or individual components of the porous structure design on distinct properties ofβ-TCP.Therefore,the alteration pattern of critical features ofβ-TCP under the combined action of metals and porous structure are ignored to a large extent.Meanwhile,there lacks an in-depth analysis of the mechanism to enhance mechanical and osteogenic properties of bioceramic materials resembling bones.This hinders laboratory findings transformed into practical applications.Therefore,our paper concentrated on the poor mechanical and osteogenic properties ofβ-TCP bioceramics.From a bionics perspective,we analyzed how Sr²⁺and Mn²⁺modification improves the performance ofβ-TCP bone-like porous bioceramics and the underlying mechanism was revealed.The mechanical,friction and wear,in vitro degradation,mineralization,cytotoxicity,antibacterial and in vivo osteogenic properties of modified porous bioceramics were studied in detail.To begin with,based on bionics principle we synthesized Sr²⁺and Mn²⁺modifiedβ-TCP powder in the ratio of（Ca+Mn）/P=1.5 through the sol-gel method inspired by the natural bone’s structural characteristics and components.Then,the powder’s surface morphology,phase composition,and particle size were systematically analyzed.The results indicated the prepared powder was pure,free of impurities,and uniformly sized.Theβ-TCP powder’s particle size distribution was relatively uniform.Adding Sr²⁺and Mn²⁺to theβ-TCP powder had minimal effect on the particle size,which remained below 40μm.Following this,this paper revealed how the mechanical properties ofβ-TCP bone-like bioceramics enhanced through the doping of Sr²⁺and Mn²⁺.A matrix of modifiedβ-TCP powder,including Sr²⁺and Mn²⁺,was combined with stearic acid as a pore-forming agent and PVA as a binder to prepare modifiedβ-TCP bone-like porous bioceramics using the pore-forming agent method.The obtained materials were then characterized using XRD,FT-IR,SEM and ICP-OES prior to mechanical property testing.The engineered porous bioceramic substance was impeccable and uncontaminated,exhibiting excellent crystalline characteristics.The doping of Sr²⁺and Mn²⁺causes a lattice distortion ofβ-TCP.The inner volume of the bone-mimetic porous bioceramic material exhibited a well-connected three-dimensional network structure,displaying significant permeability.Among all the porous bioceramic materials,the one with 30%stearic acid content demonstrated the highest porosity,with the mechanical features of 1Sr-1.5Mn-TCP surpassing all others.After that,the friction and wear mechanism of Sr²⁺and Mn²⁺modifiedβ-TCP bone-like porous bioceramics was subsequently examined.The friction and wear behaviour of bone-like bioceramics was compared under three commonly occurring lubrication conditions（dry friction,lubrication with normal saline,and simulated body fluid（SBF）solution）,revealing the effects of lubrication environment,rotational speed,and load on bioceramic friction and wear behaviour.The same material under dry friction experiences adhesive wear,abrasive wear,and fatigue wear.In contrast,SBF solution wear was predominantly comprised of abrasive wear and fatigue wear,The primary forms of wear in normal saline were corrosion wear and fatigue wear.Then,the study focused on the degradation and mineralization properties of bone-like porous bioceramics modified with Sr²⁺and Mn²⁺doping.The in vitro degradation and mineralization mechanism of the bioceramics was revealed,whereby the calcium and phosphorus ions produced by the degradation were mineralized and deposited on both the surface and inside of the material due to local saturation.The results showed that increasing the doping content of Sr²⁺and Mn²⁺enhanced mineralization deposition.The study considered the effect of pore size and porosity on the formation of bone-like apatite.Results indicated that alkaline solution in the degradation process was more favourable to the formation of bone-like apatite in bioceramics with large pore size and high porosity.Furthermore,the mechanical properties of the bone imitation bioceramics slightly declined,with 1Sr-1Mn-TCP bone imitation bioceramics exhibiting the highest Vickers hardness and compressive strength.Finally,the biocompatibility ofβ-TCP bone-like porous bioceramics modified with Sr²⁺and Mn²⁺was studied and their cytotoxic and antibacterial mechanisms were revealed.To assess its biological properties,in vitro experiments were conducted using rat bone marrow mesenchymal stem cells as the observation objects.The adhesion,proliferation and differentiation effects of bone-mimicking bioceramic surface cells were analyzed.And the cytotoxicity of modified bone-mimicking bioceramic surface cells were verifying by detecting the expression of alkaline phosphatase.The antibacterial properties of modified bone-like bioceramics were confirmed,and the most distinct antibacterial effect was observed in 1Sr-1.5Mn-TCP.In addition,an in vivo evaluation of bone repair and reconstruction was conducted using a New Zealand White rabbit femur condyle defect model with varying phase compositions of bone-like bioceramics to reveal the in vivo bone formation mechanism.At week 12,high-density bone tissue repair was observed in the bone defect area of all 5 bone-like bioceramics.Among them,1Sr-1Mn-TCP exhibited the most potent bone induction ability and was the most conducive to bone tissue growth.Based on the test results above,the bone regeneration mechanism of Sr²⁺and Mn²⁺modifiedβ-TCP bone-like porous bioceramics was proposed.The physicochemical and biological properties of bone-like bioceramics were analyzed and evaluated in a complete system by adjusting ion doping content,pore size,and porosity ofβ-TCP.Additionally,the study conducted preliminary research into organism implantation ofβ-TCP bone-like porous bioceramics.