多方式引入硅元素改性磷酸鈣骨水泥及其性能研究
發(fā)布時(shí)間：2018-10-13 18:22
【摘要】：磷酸鈣骨水泥(CPC)具有良好的可塑型性、生物相容性和生物活性以及自固化特性,被廣泛用于骨修復(fù)材料領(lǐng)域。但由于CPC存在固化時(shí)間過長(zhǎng)、力學(xué)強(qiáng)度不高、抗?jié)⑸⑿圆钜约肮钦T導(dǎo)性不足等缺點(diǎn),限制了其在臨床上的應(yīng)用。硅(Si)元素對(duì)維持機(jī)體的正常生長(zhǎng)和骨骼的形成極其重要,它參與骨的鈣化過程,尤其在新骨的形成過程中發(fā)揮著重要作用。為了克服CPC的這些缺點(diǎn),本研究將Si元素以不同形式引入CPC中,制備綜合性能優(yōu)異的含Si骨水泥,為解決CPC存在的問題探討新的途徑和方法。將無定形硅酸鈣(ACS)添加到CPC中,制備出ACS/CPC復(fù)合骨水泥。ACS的加入能夠促進(jìn)CPC的水化反應(yīng),使CPC的凝結(jié)時(shí)間縮短、抗壓強(qiáng)度提高。當(dāng)ACS的添加量為5 wt%時(shí),ACS/CPC的凝結(jié)時(shí)間比純CPC的凝結(jié)時(shí)間(40 min)縮短了11分鐘,抗壓強(qiáng)度(35.7±3.6 MPa)提高了35%,可注射性仍然保持在95%以上,滿足臨床操作的要求。ACS/CPC在模擬體液(SBF)中沉積羥基磷灰石(HA)的速度比純CPC更快,使得ACS/CPC在浸泡后期的失重率減小。細(xì)胞生物學(xué)研究表明,相比于純CPC,ACS/CPC能顯著促進(jìn)小鼠骨髓間質(zhì)干細(xì)胞(mBMSCs)和人臍靜脈內(nèi)皮細(xì)胞(HUVECs)的粘附、增殖,以及促進(jìn)mBMSCs向成骨細(xì)胞分化。在CPC中添加硅灰石(WS),對(duì)WS粉末粒徑以及含量對(duì)CPC理化性能的影響進(jìn)行了系統(tǒng)的研究。在WS顆粒尺寸大于106μm時(shí),WS/CPC的凝結(jié)時(shí)間隨著WS粒徑的增大而延長(zhǎng),抗壓強(qiáng)度下降。WS粒徑在53-106μm的WS/CPC具有更好的理化性能。因此,選擇WS的最佳粒徑范圍為53-106μm。WS能夠促進(jìn)CPC的水化反應(yīng),但不影響其水化產(chǎn)物的物相。WS的含量超過20 wt%時(shí),WS/CPC的可注射性急劇下降。在CPC中添加WS可以縮短CPC的凝結(jié)時(shí)間、提高抗壓強(qiáng)度,同時(shí)其孔隙率和可降解性有所降低。較之純CPC,含有適量WS的WS/CPC對(duì)mBMSCs和HUVECs表現(xiàn)出更好的反應(yīng)性。采用化學(xué)沉淀法在部分結(jié)晶磷酸鈣(PCCP)中摻雜Si元素,經(jīng)分析可知Si能夠進(jìn)入PCCP中的結(jié)晶相HA晶格,使晶胞參數(shù)發(fā)生改變,晶胞體積增大。少量摻雜Si使其中的HA相結(jié)晶變得較完善,晶粒主要為針狀晶體,但過量摻雜Si又會(huì)使HA的結(jié)晶性變差。將摻Si的PCCP(Si-PCCP)與DCPA混合得到Si摻雜的磷酸鈣骨水泥(Si-CPC)。相比純CPC,Si-CPC的凝結(jié)時(shí)間有所縮短,抗壓強(qiáng)度有所提高,并且Si-CPC比純CPC具有更高的生物活性。細(xì)胞學(xué)實(shí)驗(yàn)表明,相比純CPC,Si-CPC能夠顯著促進(jìn)mBMSCs和HUVECs的粘附、增殖以及mBMSCs的分化。根據(jù)上述三種含硅組分(ACS、WS和Si-PCCP)溶解度的不同,通過將三者組合來調(diào)控Si的釋放速率,制備出可控Si釋放的磷酸鈣骨水泥。同時(shí)添加兩種或者三種含Si組分的骨水泥比單一含Si組分的骨水泥具有更優(yōu)越的理化性能和細(xì)胞生物學(xué)性能,三種含Si組分共摻的骨水泥(3SiCPC)性能最優(yōu)。3SiCPC在SBF中降解14天后達(dá)到平衡,溶液中的Si濃度變化較小,在28天內(nèi)基本保持穩(wěn)定在較高的濃度值。培養(yǎng)基中Si濃度在適當(dāng)范圍內(nèi)時(shí),多種含Si組分共摻的CPC具有更好的細(xì)胞反應(yīng)性。通過在上述可控Si釋放的磷酸鈣骨水泥3SiCPC中添加槐豆膠(LBG)和多巴胺(DA)作為抗?jié)⑸?制備了抗?jié)⑸⑿粤己玫目勺⑸湫土姿徕}骨水泥。這兩種抗?jié)⑸┑奶砑泳苊黠@改善3SiCPC的抗?jié)⑸⑿�。在LBG含量不超過1.0 wt%時(shí),3SiCPC的凝結(jié)時(shí)間稍有延長(zhǎng)、抗壓強(qiáng)度和可注射性略有降低。并且,含有1.0 wt%LBG的3SiCPC對(duì)mBMSCs表現(xiàn)出良好的細(xì)胞相容性。當(dāng)DA的添加量不超過0.4 wt%時(shí),3SiCPC的凝結(jié)時(shí)間稍有延長(zhǎng),抗壓強(qiáng)度略有提高。相比純3SiCPC,含有0.4 wt%DA的3SiCPC更有利于蛋白的吸附,對(duì)mBMSCs和HUVECs具有更好的細(xì)胞響應(yīng)。
[Abstract]:Calcium phosphate cement (CPC) has good formability, biocompatibility and bioactivity, as well as self-curing properties, and is widely used in the field of bone repair materials. However, due to the long curing time of CPC, the mechanical strength is not high, the fracture resistance is poor and the osteoinducibility is insufficient and so on, the application of the CPC in clinic is limited. Silicon (Si) element plays an important role in maintaining the normal growth of the body and the formation of bone, it participates in the calcification process of bone, especially plays an important role in the formation of new bone. In order to overcome these disadvantages of CPC, this study introduces Si elements into CPC in different forms, prepares Si-containing cement with excellent comprehensive properties, and discusses new ways and methods for solving the problems of CPC. An ACS/ CPC composite bone cement was prepared by adding amorphous calcium silicate (ACS) into CPC. The addition of ACS can promote the hydration reaction of CPC, shorten the coagulation time of CPC and improve the compressive strength. When the addition amount of ACS is 5 wt%, the coagulation time of ACS/ CPC is shortened by 11 minutes compared with the coagulation time (40 min) of pure CPC, the compressive strength (35. 7 MPa 3. 6 MPa) is improved by 35%, the injectability is still kept above 95%, and the requirement of clinical operation is met. ACS/ CPC deposited hydroxyapatite (HA) in simulated body fluid (SBF) faster than pure CPC, so that the weight loss rate of ACS/ CPC in late infusion was decreased. Cell biological studies have shown that ACS/ CPC can significantly promote the adhesion and proliferation of bone marrow mesenchymal stem cells (mBMSCs) and human umbilical vein endothelial cells (HUVECs) in mice compared with pure CPC, and promote the differentiation of mBMSCs into osteoblasts. The influence of particle size and content of WS powder on the physical and chemical properties of CPC was studied by adding wollastonite (WS) in CPC. When the size of WS particles is larger than 106. m u.m, the coagulation time of WS/ CPC is extended with the increase of WS particle diameter and the compressive strength decreases. WS particle size is 53-106. m u.m and WS/ CPC has better physical and chemical properties. Therefore, the optimum particle size range of the selected WS is 53-106. m u.m. WS can promote the hydration reaction of CPC, but does not affect the product phase of its hydration product. When the content of WS exceeds 20 wt%, the injection properties of WS/ CPC are drastically reduced. Adding WS to CPC can shorten the coagulation time of CPC, improve the compressive strength, and decrease its porosity and degradability. Compared with pure CPC, WS/ CPC containing a proper amount of WS showed better reactivity to mBMSCs and HUVECs. Si element is doped in partial crystalline calcium phosphate (PCCP) by chemical precipitation method. Through analysis, Si can enter crystalline phase HA crystal lattice in PCCP, change cell parameters and increase unit cell volume. With a small amount of Si doped with Si, the crystal of HA phase becomes more perfect, and grains are mainly needle-like crystals, but excessive doping of Si can lead to poor crystallinity of HA. Si-doped calcium phosphate cement (Si-CPC) was obtained by mixing Si-PCCP and DCPA. Compared with pure CPC, the condensation time of Si-CPC is shortened, the compressive strength is improved, and Si-CPC has higher bioactivity than pure CPC. The cytology test showed that compared with pure CPC, Si-CPC could significantly promote the adhesion, proliferation and differentiation of mBMSCs and HUVECs. According to the different solubility of the three silicon-containing components (ACS, WS and Si-PCCP), calcium phosphate cement with controllable Si release was prepared by combining the three combinations to control the release rate of Si. At the same time, the bone cement with two or three Si-containing components has better physical and chemical properties and cell biological properties than bone cement with a single Si-containing component, and the three-Si-containing co-doped bone cement (3SiCPC) performance is optimal. 3SiCPC is equilibrated in SBF for 14 days, the concentration of si in the solution is small and remains substantially stable over 28 days at higher concentration values. When the concentration of Si in the culture medium is within proper range, a variety of CPC containing Si-containing components has better cell reactivity. The injectable calcium phosphate cement was prepared by adding locust bean gum (LBG) and dopamine (DA) into the calcium phosphate cement 3SiCPC released by the controllable Si as an anti-collapse agent. The addition of these two anti-crush agents can obviously improve the anti-sibility of 3SiCPC. When the LBG content does not exceed 1. 0% by weight, the coagulation time of 3SiCPC is slightly prolonged, and the compressive strength and injectability are slightly reduced. Also, 3SiCPC containing 1.0 wt% LBG exhibited good cell compatibility to mBMSCs. When the addition amount of DA is not more than 0.4 wt%, the coagulation time of 3SiCPC is slightly prolonged, and the compressive strength is slightly improved. Compared with pure 3SiCPC, 3SiCPC containing 0.4 wt% DA is more favorable for protein adsorption, and has better cell response to mBMSCs and HUVECs.
【學(xué)位授予單位】：華南理工大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R318.08
，
本文編號(hào)：2269520
[Abstract]:Calcium phosphate cement (CPC) has good formability, biocompatibility and bioactivity, as well as self-curing properties, and is widely used in the field of bone repair materials. However, due to the long curing time of CPC, the mechanical strength is not high, the fracture resistance is poor and the osteoinducibility is insufficient and so on, the application of the CPC in clinic is limited. Silicon (Si) element plays an important role in maintaining the normal growth of the body and the formation of bone, it participates in the calcification process of bone, especially plays an important role in the formation of new bone. In order to overcome these disadvantages of CPC, this study introduces Si elements into CPC in different forms, prepares Si-containing cement with excellent comprehensive properties, and discusses new ways and methods for solving the problems of CPC. An ACS/ CPC composite bone cement was prepared by adding amorphous calcium silicate (ACS) into CPC. The addition of ACS can promote the hydration reaction of CPC, shorten the coagulation time of CPC and improve the compressive strength. When the addition amount of ACS is 5 wt%, the coagulation time of ACS/ CPC is shortened by 11 minutes compared with the coagulation time (40 min) of pure CPC, the compressive strength (35. 7 MPa 3. 6 MPa) is improved by 35%, the injectability is still kept above 95%, and the requirement of clinical operation is met. ACS/ CPC deposited hydroxyapatite (HA) in simulated body fluid (SBF) faster than pure CPC, so that the weight loss rate of ACS/ CPC in late infusion was decreased. Cell biological studies have shown that ACS/ CPC can significantly promote the adhesion and proliferation of bone marrow mesenchymal stem cells (mBMSCs) and human umbilical vein endothelial cells (HUVECs) in mice compared with pure CPC, and promote the differentiation of mBMSCs into osteoblasts. The influence of particle size and content of WS powder on the physical and chemical properties of CPC was studied by adding wollastonite (WS) in CPC. When the size of WS particles is larger than 106. m u.m, the coagulation time of WS/ CPC is extended with the increase of WS particle diameter and the compressive strength decreases. WS particle size is 53-106. m u.m and WS/ CPC has better physical and chemical properties. Therefore, the optimum particle size range of the selected WS is 53-106. m u.m. WS can promote the hydration reaction of CPC, but does not affect the product phase of its hydration product. When the content of WS exceeds 20 wt%, the injection properties of WS/ CPC are drastically reduced. Adding WS to CPC can shorten the coagulation time of CPC, improve the compressive strength, and decrease its porosity and degradability. Compared with pure CPC, WS/ CPC containing a proper amount of WS showed better reactivity to mBMSCs and HUVECs. Si element is doped in partial crystalline calcium phosphate (PCCP) by chemical precipitation method. Through analysis, Si can enter crystalline phase HA crystal lattice in PCCP, change cell parameters and increase unit cell volume. With a small amount of Si doped with Si, the crystal of HA phase becomes more perfect, and grains are mainly needle-like crystals, but excessive doping of Si can lead to poor crystallinity of HA. Si-doped calcium phosphate cement (Si-CPC) was obtained by mixing Si-PCCP and DCPA. Compared with pure CPC, the condensation time of Si-CPC is shortened, the compressive strength is improved, and Si-CPC has higher bioactivity than pure CPC. The cytology test showed that compared with pure CPC, Si-CPC could significantly promote the adhesion, proliferation and differentiation of mBMSCs and HUVECs. According to the different solubility of the three silicon-containing components (ACS, WS and Si-PCCP), calcium phosphate cement with controllable Si release was prepared by combining the three combinations to control the release rate of Si. At the same time, the bone cement with two or three Si-containing components has better physical and chemical properties and cell biological properties than bone cement with a single Si-containing component, and the three-Si-containing co-doped bone cement (3SiCPC) performance is optimal. 3SiCPC is equilibrated in SBF for 14 days, the concentration of si in the solution is small and remains substantially stable over 28 days at higher concentration values. When the concentration of Si in the culture medium is within proper range, a variety of CPC containing Si-containing components has better cell reactivity. The injectable calcium phosphate cement was prepared by adding locust bean gum (LBG) and dopamine (DA) into the calcium phosphate cement 3SiCPC released by the controllable Si as an anti-collapse agent. The addition of these two anti-crush agents can obviously improve the anti-sibility of 3SiCPC. When the LBG content does not exceed 1. 0% by weight, the coagulation time of 3SiCPC is slightly prolonged, and the compressive strength and injectability are slightly reduced. Also, 3SiCPC containing 1.0 wt% LBG exhibited good cell compatibility to mBMSCs. When the addition amount of DA is not more than 0.4 wt%, the coagulation time of 3SiCPC is slightly prolonged, and the compressive strength is slightly improved. Compared with pure 3SiCPC, 3SiCPC containing 0.4 wt% DA is more favorable for protein adsorption, and has better cell response to mBMSCs and HUVECs.
【學(xué)位授予單位】：華南理工大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R318.08
，
本文編號(hào)：2269520
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