單相、雙相及多相離子摻雜的羥基磷灰石研究進展

劉瑩，楊瑞，劉井來，劉佳欣，張靖羚

單相、雙相及多相離子摻雜的羥基磷灰石研究進展

劉瑩1a，楊瑞1b，劉井來2，劉佳欣1b，張靖羚1b

（1.遼寧工程技術大學 a.理學院 b.材料科學與工程學院，遼寧 阜新 123000；2.甘李藥業股份有限公司，北京 101102）

羥基磷灰石是天然骨組織成分中的重要組成部分，一直是生物醫學領域關注和研究的重點。天然骨成分中的磷灰石，是一種結合著多種離子的羥基磷灰石，維持著生命系統的正常生長與發育。本研究闡述了羥基磷灰石的晶體結構；概述了研究者針對羥基磷灰石性能探究，其中包括生物相容性、生物活性、適宜的機械強度、優異的成骨性能和耐腐蝕性能。同時歸納了離子摻雜羥基磷灰石取代位點。在此基礎上，重點闡述了近五年來單相、雙相以及多相摻雜羥基磷灰石材料的研究，其中包括單相、雙相以及多相離子摻雜對羥基磷灰石在結構性能、機械強度、抗菌性、降解性和成骨性等性能的影響，同時簡單總結了離子摻雜對機械強度的影響規律。近年來雖然羥基磷灰石生物陶瓷材料在臨床上作為植入物涂層、緩釋藥物的載體、骨移植物代替材料等被應用，但在臨床方面廣泛運用還面臨著許多問題與挑戰，所以本文同時展望了離子摻雜羥基磷灰石未來的的發展方向，有望在臨床應用及發展方面有一定的指導意義。

羥基磷灰石；離子摻雜；抗菌性；機械強度；植入物涂層；治療癌癥

羥基磷灰石（HA，Ca10(PO4)6(OH)2）是一種與哺乳動物硬組織組成非常相似的合成生物陶瓷材料，因此被廣泛應用于骨移植、骨修復、硬組織工程支架和金屬基材的涂層等方面[1-2]。HA中鈣磷比為1.67，晶型常態屬于六方晶系，穩定相為單斜晶相（一般高溫熱處理后），L6PC對稱型和63/空間群。晶胞參數為==0.943～0.938 nm，=0.688～0.686 nm，==90°，=120°，每個晶胞中包含10個Ca2+、6個PO43?和2個OH?，圖1為HA晶體結構示意圖。

圖1 HA晶體結構示意圖

早在1951年，RD Ray等合成了適用于骨缺損治療領域的HA；直至1980年，de K Groot等相繼合成了HA，并應用于整形外科[3]。人工合成的HA具有良好的生物活性、生物相容性、適宜的機械強度、成骨性和耐腐蝕性等[4]。王艷玲等[5]通過微弧氧化法在金屬鈦無牙區種植體表面制備了HA涂層，發現HA可以促進成骨細胞的黏附和外周骨質的生成，從而誘導骨的形成。T. M等[6]通過射頻磁控濺射法在AZ91鎂合金表面制備了HA涂層，研究發現涂層可以控制降解速率，提高AZ91合金的生物相容性和生物礦化能力。楊蕾等[7]利用微弧氧化技術（MAO）在AZ31鎂合金表面制備出含有納米級別的n-HA涂層，該涂層能對多孔形態進行填充，體現優異的耐腐蝕效果，在體外細胞培養實驗中，細胞粘附和細胞誘導效果明顯強于無涂層的樣品，能夠促進成骨細胞的增殖分化。Jiang等[8]通過水熱法在鈦合金表面覆蓋了一層HA涂層，研究發現涂層樣品耐蝕性優于未涂層樣品，因此植入材料具有良好的生物相容性和骨誘導性。但是HA涂層的脆性和不易降解性限制了其應用[9-10]。

研究發現，生物體內的磷灰石是一種晶體結構不完善的HA，其中結合一些很多微量元素，例如Na+、Mg2+、Zn2+、Cl?、CO32?、F?等離子[11-12]，因此研究者們在人工合成HA時會有選擇性的摻入一些離子，通過離子半徑的變化改變晶格參數，從而在模擬生物礦化的基礎上改進HA的各項性能。

離子摻雜可以分為陰離子摻雜與陽離子摻雜。陽離子摻雜是指HA中的Ca2+可被某些二價的陽離子（如Mg2+[13-15]、Zn2+[16-19]、Sr2+[20-23]、Fe2+[24-27]、Cu2+[28-32]、Ni2+[33-34]等）部分或全部取代，也可被單價和三價的陽離子（如Na+[35-37]、K+[35,38]、Fe3+ [24-25,39]、Eu3+[40-44]等）部分取代。陰離子摻雜可分為A和B兩種類型的取代，A是在羥基位點的取代，一般為OH?被Cl?、F?[45-46]、Br?等離子的取代；而B則是PO43?被CO32?[24,44-45]、VO43?[46-47]和SiO44?[48]等部分或全部取代，此取代方式為磷酸根位點的取代，當然A、B同時取代也是存在的。研究者們通過單相摻雜綜合分析，對雙相及多相離子摻雜的HA進行了多方向多角度的設想、制備與研究。

本文選材多為離子摻雜HA作為涂層材料改善金屬植入物性能的研究，以更好地滿足骨移植和骨修復領域的臨床需求。合金材料表面附著的離子摻雜HA涂層材料，為合金材料提供機械強度和可降解性能，而離子摻雜在通過改變HA涂層結構和調控涂層與合金之間的關系來增強植入物的生物活性、生物相容性和抗菌性等生物性能。

1 單相離子摻雜羥基磷灰石的制備與發現

目前，關于單相離子摻雜已經形成系統的研究，下面簡單對幾種常見且代表性較強的單相離子摻雜HA的案例進行敘述。

M等[45]通過低溫共沉淀法和水熱輔助溶膠凝膠法相結合分別制備了HApMn、HApFe、HApCo、HApNi、HApCu、HApZn和純HAp，發現HAp-Mn、HAp-Fe和HAp-Ni與CaHAp相的PDF文件(00- 009-0432)一致，當Mn4+、Fe2+加入與CaHAp相對應的主峰強度降低，而當Co+、Cu2+和Zn2+加入時主峰相發生偏移至2=26.04°，說明離子的加入在一定程度會降低羥基磷灰石的結晶度。研究表明離子的加入一般會降低HA的結晶度，但均無其他雜相存在（見圖2）。Mg2+摻雜HA可以促進骨和血管形成[46-47]，對銅綠假單胞菌、金黃色葡萄球菌和白色念珠菌有較好的的抗菌功效，但Mg-HA在形成涂層的過程中存在著穩定性較差的弱點[48]。Fe2+摻雜會使HA納米粒子具有超順磁性，通過外加磁場力的作用可以促進降解和推動礦化過程，從而促進細胞的增殖與 分化[49-52]。

圖2 CaHA、HAMn、HAFe、HACo、HANi、HACu和HAZn的X射線衍射圖譜[45]

Balak等[53]通過水熱法制備純HA和Fe-HA（Fe2+為變量），發現Fe2+的加入改善了HA的晶粒尺寸，最小的尺寸可達19.7 nm，顯現為球形結構（見圖3）。磁性測試發現Fe-HA飽和磁化強度最強為0.029 emu/g；但是微量Fe的加入可能會產生輕微的溶血現象，以及研究中只體現了硬度的改善，不足以體現Fe2+的加入提高了HA的力學性能。

Yazici等[54]采用MAO技術在可降解的Mg-Sr-Ca合金表面制備了Ag-HA涂層。該涂層具有良好的生物活性和耐腐蝕性能，Ag+的增加明顯增強了HA涂層的抑菌性，但抗菌實驗中抗菌率達到100%時，Ag+的濃度已經超過其在生物體中的極限濃度，會產生嚴重的細胞毒性。而且在體液浸泡實驗中，隨著Ag+濃度的增加，表面沉積的Sr-HA與Ag-HA之間可能存在應力作用，使涂層表面出現了明顯的裂紋。

Taolei等[55]采用水熱法在ZK60鎂合金表面制備了Sr-HA納米棒/納米線涂層。ZK60鎂合金為植入物提供了良好的可生物降解性，Sr-HA涂層具有較好的耐腐蝕性能，Sr2+的存在提高了HA涂層的成骨性和生物相容性。但是水熱法合成的HA與鎂合金之間是否存在應力缺陷還值得考究。

Sergi等[56]采用前驅體等離子噴涂法制備了鋅摻雜羥基磷灰石涂層（Zn-HA），發現Zn-HA涂層對人成骨細胞Saos-2細胞無細胞毒性，對金黃色葡萄球菌（）和大腸桿菌（）均表現出較強的抗菌作用（見圖4）。

圖3 水熱合成的HA與10FeHA的形貌[53]

Zhou等[57]采用水熱法在ZK60鎂合金表面制備了Zn-HA涂層。研究發現鋅的加入改變了鍍層的形貌，使其表面出現了納米晶須結構，并發現此植入物具有良好的成骨分化能力、抑菌能力和耐腐蝕特性。但是Zn2+的摻入量明顯影響HA的穩定性，過量會有α-磷酸三鈣相存在，這個結果可能與溫度有關[58-59]。

Benjamín等[60]采用水熱法制備了Si-HA。研究發現Si-HA的結晶度較高，呈現為35～80 nm的棒狀結構，當SiO44?達到一定濃度時，高溫燒結后的HA顆粒之間會出現SiO2的小玻璃區域。但Si的實際摻入量僅為目標摻入量的60%左右，并且沒有表明小玻璃區域出現對涂層性能的影響。

Maryam等[61]采用熱物理混合燒結法制備了SiO2-HA，發現有SiO44?摻入到HA中，得到的結論是適當的Si摻雜量會提高HA的生物可降解能力和礦化能力，原因是制備過程中有溶解度高于HA的磷酸三鈣（TCP）和硅酸鈣（Ca2SiO4）相的產生，使得到的類羥基磷灰石材料致密性增強。但物理混合法可能會導致材料部分位置存在應力缺陷，且在燒結過程中溫度變化對SiO2-HA產生的Si-HA的分解程度不明確。還有研究發現Si-HA涂層具有較好的生物活 性[62]，它可以增強成骨細胞活性，同時降低破骨細胞活性，說明Si-HA能減緩破骨細胞分化和骨重塑速率，這對骨質疏松癥有著十分重要的意義[63]。

Nasker等[64]采用水熱法制備了不同濃度氟摻雜n-HA(F-HA)和純n-HA，合成的納米顆粒形貌大多呈均勻規則的納米棒狀，雖然有氟化鈣雜相出現，但是F?的存在顯著的改善了n-HA的結晶度與結構穩定性，還發現F-HA有一定的殺菌效果并且粉末無細胞毒性（見圖5）。而且F?摻雜n-HA在一定程度上可增加成骨細胞活性，促進骨細胞生長、增殖與分化，從而起到誘導骨形成的作用[65-66]。

碳酸根摻雜HA(CHA)，CO32?可以取代OH?或PO43?分別進行A或B取代，也可以同時進行AB取代，研究發現人工合成的CHA一般以B取代為主[67-68]。CO32?取代可以降低HA的結晶度和熱穩定性，提高HA的溶解性[69]，CO32?摻雜羥基磷灰石塊體和涂層樣品在模擬生理溶液中均可形成類骨碳酸羥基磷灰石礦化層[70]。

上述單相離子摻雜HA可以在一定程度上修飾HA的性能，但還不能滿足臨床應用的需求，筆者認為尚有下述問題需要解決：（1）在產物為純相的前提下，結晶度和晶粒尺寸是否均可被改善；（2）抗菌性作用是否可以同時高效針對多種細菌；（3）生物可降解性是否可以調控；（4）離子摻雜是否可以有效改善HA的脆性。

這些問題可以在單相離子摻雜HA的基礎上，通過調整制備工藝、反應物濃度和反應條件等來探究，與此同時為得到優良的綜合性能，嘗試復合離子摻雜HA也已經成為了研究的熱點。

圖5 48 h內各個樣品在E.coli和S.aureus兩種菌株存在環境中的培養情況[64]

Fig.5 The culture situation of each sample in the presence of E.coli and S.aureus within 48 h[64]

2 雙相離子摻雜羥基磷灰石的發展與應用

基于現代生物材料的理念，對于毒性、安全性、機械強度、降解性、成骨性、可塑性等性能的把控，是滿足機體不同部位骨修復與骨移植的必要條件。雙相離子摻雜HA通過制備技術優化和應用效果改善，來適應天然骨性能和臨床的要求。

Cao等[71]通過脈沖激光沉積技術在金屬鈦植入物表面制備Mg-F-HA涂層。模擬體液浸泡7 d后涂層內部結構為類似于松質骨的有序線性結構，浸泡14 d后，涂層完全被新形成的磷灰石層覆蓋，表面光滑，干燥過程中應力釋放出現少量裂痕，Mg-F-HA涂層可以長期保持良好的生物相容性與生物活性，可以在一定程度上調節生物降解速率和促進細胞增殖，但涂層裂痕會使涂層與基體之間存在較大程度的應力隱患（見圖6）。

Veerla等[72]采用共沉淀法制備了Ag-Fe-HA納米顆粒，研究發現控制濃度變化會使樣品形貌顯現為球形、棒狀和片狀，Ag-Fe-HA樣品具有超順磁性，將納米顆粒分別在普通細胞（HEK-293）培養皿和癌細胞（HeLa）培養皿上進行培養（見圖7），發現Ag-Fe-HA的存在幾乎對細胞沒有影響，而癌細胞長度明顯變長，在50Ag50Fe-HA的存在下HeLa細胞的細胞膜似乎被破壞，細胞發生了劇烈變化如圖8b4，表明Ag-Fe-HA納米顆粒能夠有效靶向殺傷癌細胞，且對正常細胞幾乎無毒副作用。但是此研究中銀離子與亞鐵離子的實驗組尚未確定Ag+和Fe2+的最佳組合濃度，可以在后續研究中對其進行深入。

Seyed等[73]采用溶膠凝膠法制備了一種原位硅包覆硅酸根與碳酸根摻雜的HA納米粉體（Si-S- C-HA）。通過表征發現非晶態SiO2包覆層的存在促進HA在生理鹽水中離子的釋放，使S-C-HA納米顆粒懸浮在溶液中且帶負電荷，說明非晶態SiO2層可以加速S-C-HA的生物礦化與改善細胞附著，但是正是由于表面帶負電荷會吸引樣品中的陽離子，這樣會不會影響樣品中HA結構和性能的變化有待研究。

Abbas等[74]采用機械化學合成方法制備了HA- Cl-F，隨著陰離子的雙重取代OH?，樣品的晶粒尺寸、結晶度和單位細胞體積呈非線性增大，晶格應變逐漸減小，由于粉末的比表面積大和范德華力相互作用，研磨后的樣品具有較高的團聚傾向，納米粒子呈現為多邊形和球形組成的簇狀結構，而在高溫煅燒后顆粒逐漸呈等軸狀，在退火過程中，由于殘余彈性應變的大幅度減小，導致晶粒長大；驚奇的是TEM觀察得到的晶粒尺寸范圍類似于天然骨的20～40 nm范圍[75]（見圖8）。而且發現樣品在堿性、酸性和中性條件下zeta電位均為負，負zeta電位的存在在一定程度上有利于骨整合、磷灰石成核和骨再生。

圖6 SBF溶液浸泡7、14 d后Mg-F-HA涂層微觀結構[71]

圖7 HEK-293、HeLa與納米顆粒培養24 h的高倍（100倍）相位差顯微鏡圖像（a1、b1表示細胞本身，a2、b2表示HA，a3、b3表示25Ag25Fe-HA，a4、b4表示50Ag50Fe-HA）[72]

Yong等[76]通過電沉積與陽極氧化在利用二氧化鈦納米管(TN)改性的金屬Ti表面上沉積了一種新型的摻銀羥基磷灰石/硅酸鈣（AgHA/CS）層，此涂層實際上存在的離子交換形式是Ag+和SiO32?與HA中離子進行替換，即是另一種意義上的Ag-Si-HA涂層，AgHA/CS涂層表面形貌呈現多孔網狀結構，具有這樣的網絡結構膜適合于關節和牙齒的修復[77]（見圖9），與純HA涂層相比，該涂層具有優異的耐腐蝕性，在對S.aureus的抑制實驗中體現出較強的抗菌作用，除此之外，Ag-Si-HA涂層還有利于成骨細胞的附著、增殖與分化。但這樣的結構是否存在較大程度的應力缺陷未能體現。電沉積的HA層是均勻的，形態顯現為花簇或針狀晶體，表面形貌的變化可能是由于Ag+的取代CS（殼聚糖）在HA中的結合。盡管復合涂層中的多孔結構可以降低其機械性能，但它通常有利于成骨細胞向陶瓷復合物中的生長，從而增加骨整合性，這說明在多孔網狀結構存在的情況下材料依然可以保持良好的機械性能。這是否說明復合涂層與基體之間存在著某種界面效應影響了涂層與基體的性能？

圖8 機械研磨60 min的樣品常溫和煅燒后的形貌SEM圖與樣品A1、A2和A3的TEM圖譜[74]

圖9 AgHA/CS涂層表面形貌（a—c），HA涂層表面（d，e），AgHA/CS涂層厚度的橫截面圖像（f）[76]

M. K等[78]通過脈沖激光沉積法在氧化鋁表面制備了金和碳酸根摻雜的羥基磷灰石（Au-C-HA)涂層。研究發現，HA粒子呈現為250～450 nm的球狀結構。隨著Au+的增加，剪切模量有明顯變化的趨勢（先變大后減小），彈性模量逐漸變小但變動很小，而顯微硬度會變大，變化范圍為31～34 Gpa，說明Au+的加入可以在一定程度上改善HA涂層的力學性能（見表1）。在對HFB4細胞系培養的實驗中發現，Au+的加入增強了支架表面的細胞粘附性，使細胞不僅在涂層的表面擴散與生長，同時在涂層的孔隙結構中也不斷地進行著增殖和分化。

Wei等[79]研究了化學沉淀法制備的Se-Sr-HA結構性能和生物性能，發現SeO32?和Sr2+的共同加入得到了純羥基磷灰石相、降低了Se-Sr-HA的結晶度、減小了晶粒尺寸，Sr2+的加入影響了樣品的熱穩定性；細胞培養實驗顯示，Se-Sr-HA對小鼠骨髓間充質干細胞（mBMSCs）無毒副作用，而其對人成骨肉瘤細胞（MG63）有明顯的抑制作用，并發現Sr2+對MG63無影響，真正抑制它的是SeO32?，而Sr2+卻可以促進SeO32?的釋放，間接的對MG63起到了雙重抑制作用，所以Se-Sr-HA有望成為骨癌患者的治療及修復的雙功能材料。Sr2+是否對其他離子的釋放均有促進作用，這將是后續研究中較為重要的方向。

表1 各個涂層的剪切模量（）、體積模量（）、楊氏模量（）和顯微硬度（）的變化[78]

Tab.1 Changes in shear modulus (G), bulk modulus (K), Young's modulus (E) and microhardness (H) of each coating[78]

綜上所述，雙相離子摻雜的羥基磷灰石（X-Y- HA，X和Y表示未知離子）可以在多個角度影響HA性能，X-Y-HA根據臨床的實際需要可以應用到植入物表面涂層、藥物緩釋、骨修復、牙齒美容和癌癥治療等方面，雖然與天然骨材料仍然有一定程度的差距，但雙相離子摻雜在醫學和科研領域必定會有深遠的應用前景和發展前景。

3 多相離子摻雜羥基磷灰石的研究與展望

單相和雙相離子在結構性能、力學性能、抗菌性能和成骨性能等多個方面體現了離子摻雜對HA影響，然而多相離子摻雜可以站在仿生的角度改性HA，多個離子同時存在的HA擁有和天然骨磷灰石更加接近的結構與性能，將可能是未來骨修復領域研究與應用的重點。在雙相離子摻雜HA中Sr-F-HA在一定條件下可以促進成骨細胞的生長、增殖和分化，那么在其基礎上多一相或者（≥2）相是否依然存在這樣的性能甚至更多的影響呢？

Gao等[80]通過水熱法合成了Sr2+、F?和SiO44?共摻雜的羥基磷灰石（Sr-F-Si-HA）。研究發現制備產物為純HA且結晶度優于HA，在對MG63細胞進行培養過程中，發現其促進MG63的粘附和增殖的能力強于HA，說明Sr2+、F?和SiO44?的加入確實增加了HA的骨傳導性。然而前面說過SiO44?在單獨摻雜羥基磷灰石時還會增加HA的抗斷裂韌性與彎曲強度，今后可以對Sr-F-Si-HA的機械性能進行進一步的研究。

Monika等[81]使用脈沖電流在鈦合金材料（Ti6Al4V）表面沉積制備了Ag-Zn-Mg-Sr-HA（m-HA）涂層。涂層顯現為和天然骨的結構相似的多孔海綿狀結構（見圖10），經計算產物中Ca/P為1.55，說明HA晶體結構被破壞或出現CaP其他雜質相，通過將成骨MG-63細胞接種到樣品表面的實驗發現，細胞活力值明顯高于裸植入物（Ti6Al4V）和HA涂層的鈦合金材料，且活細胞在涂層表面致密性與黏附度良好，形態正常且均勻，說明m-HA涂層可以促進成骨細胞的生長發育。

圖10 m-HA涂層的不同位置的橫斷面形貌圖（a，b）和EDX能譜圖像（c）[81]

Mirna等[82]采用簡單沉淀法分別制備了Mg- Mn-Sr-HA。發現Mg2+和Mn5+在摻雜過程中很難進入HA晶格中，即使有進入，量也是相對較少的，而Sr2+很容易加入HA晶格中，并且三者同時摻雜HA時MnO43?和Mg2+的摻入量濃度很高，而Sr2+在Mg-Mn-Sr-HA中的摻入量卻明顯低于Sr-HA，這恰恰表明HA的多相離子共摻雜是一個高度復雜的過程，所以在多相離子摻雜HA的研究過程中對其摻雜結構變化與機理的分析是十分必要的，有利于更多相離子摻雜HA在類骨仿生骨修復領域的研究。然而，多相離子的共同摻雜是否存在著離子之間的相互作用致使性能的改變，Sr2+的促進作用是否時刻存在，并且是否存在先后順序，其他金屬陽離子是否也存在這種作用，或者同時摻入單相甚至多相陰離子結果又如何呢？

Vu等[83]采用等離子體噴涂方法在金屬鈦合金材料表面制備HA涂層和ZnSiAg-HA涂層。研究發現涂層與基材之間有很強的結合且在基材上保持完整，在磷酸鹽緩沖液（PBS）和pH為5的醋酸緩沖液（ABS）中Ag+總釋放量分別為0.000 171%、0.001 870%，這是由于酸性條件下增加了HA的降解速率。摻雜涂層在中性環境下同HA涂層均可長期存在，在酸性條件下14 d后HA涂層完全消失，而ZnSiAg-HA涂層仍有部分存在，說明ZnSiAg-HA涂層具有更好的結晶度；通過大鼠股骨遠端模型分析基材本身、HA涂層和ZnSiAg-HA涂層假體的早期骨整合。到第5周，摻雜涂層顯示68%的總骨形成，而HA涂層只有55%，ZnSiAg-HA涂層能產生32%的骨礦化，而HA涂層僅能產生11%的骨礦化，說明ZnSiAg-HA涂層的骨結合能力相對較強。該系統可應用于矯形、牙齒置換以及翻修手術，以促進早期種植體骨整合，縮短愈合時間。

多相離子摻雜HA的研究并不豐富，原因可能是多離子取代HA的過程與結構變化太為復雜，但是由于天然骨磷灰石中多種微量離子的存在，那么人工合成的多相離子摻雜HA的研究就必須深入。

4 總結

本研究總結了單相、雙相及多相離子摻雜羥基磷灰石對HA的性能的影響，但是和天然骨磷灰石相比仍然存在差距，多相離子摻雜HA的研究還不夠深入，對于天然骨磷灰石的多種離子成分的存在，我認為后續的研究可以根據天然骨磷灰石中各離子所占比例進行摻雜制備類骨磷灰石材料，還可以通過控制大多數離子的占比，進行單相離子或多相離子比例的動態浮動改變HA的晶粒尺寸、拓撲結構、化學成分、結晶度和表面電荷，從而達到深層次改性的效果，而且在此基礎上改變制備方法和反應條件或許可以更加接近仿生的目的。總之，在未來骨的再生和修復臨床中，納米羥基磷灰石材料將會起到關鍵性的作用，所以離子摻雜改性HA達到符合臨床要求的研究更加需要進一步開展。

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Hydroxyapatite Nanomaterials Doped with Single-phase,Dual-phase and Multiphase Ions

1a1b,2,1b,1b

(1. a. College of Science, b. College of Materials Science and Engineering, Liaoning Technical University, Liaoning Fuxin 123000, China; 2. Ganli Pharmaceutical Co., Ltd., Beijing 101102, China)

Hydroxyapatite is an important part of natural bone tissue composition and has always been the focus of attention and research in the field of biomedicine. The apatite in the natural bone composition is a kind of hydroxyapatite combined with a variety of ions, which maintains the normal growth and development of life systems. With the systematic research on single-phase ion doping, the preparation and performance of dual-phase and multi-phase doped hydroxyapatite are being continuously expanded. The preparation and performance of phase and heterogeneous ion-doped hydroxyapatite are systematically elaborated and summarized.

This study expounds the crystal structure of hydroxyapatite, describes the advantages and performance advantages of synthetic hydroxyapatite itself, hydroxyapatite with good biological properties as a coating has been widely used in experiments to replace bone, but Some performance deficiencies limit its application. The study outlines the researchers' research on the effects of different ion doping or different forms of doping on the properties of hydroxyapatite, including biocompatibility, biological activity, suitable mechanical strength, excellent bone formation performance and corrosion resistance performance. At the same time, the different substitution sites of anion and cation doped hydroxyapatite are summarized.

On this basis, starting from the preparation and performance research of single-phase ion-doped hydroxyapatite, the performance changes caused by different ion doping and the corresponding mechanism are explained. Prospects and shortcomings. Based on the single-phase ion-doped hydroxyapatite in the past five years, it is necessary to explore the effects of two-phase and multi-phase ion-doped hydroxyapatite on the structural properties, mechanical strength, antibacterial properties, degradability, and osteogenic properties. A certain pavement. At the same time, two-phase and multi-phase ion doping of hydroxyapatite found that the doping ions will promote each other. By doping hydroxyapatite in different phases, it is found that the performance of multi-phase doping is based on the synergistic effect of single-phase or multi-phase doping. In addition, the doping of hydroxyapatite with trace ions can promote the activity of bone cells, promote the growth, proliferation and differentiation of bone cells, and thus play a role in inducing bone formation. However, doping with different ions will produce different properties. The doping of hydroxyapatite with magnesium, iron, zinc, strontium, and fluorine will produce different degrees of antibacterial properties against Escherichia coli or Staphylococcus aureus. Part of the ions doped with hydroxyapatite will increase the mechanical properties of the material and increase the degradation performance.

Through more systematic preparation and performance research of single-phase and dual-phase doped hydroxyapatite, a more effective preparation method has been explored for realizing multiphase doped hydroxyapatite. In recent years, although hydroxyapatite bioceramic materials have been used clinically as implant coatings, sustained-release drug carriers, and bone graft replacement materials, they still face many problems and challenges in their widespread use in clinical practice. Therefore, this article also looks forward to the future development direction of ion-doped hydroxyapatite, paving the way for exploring the preparation method and performance of heterogeneous ion-doped hydroxyapatite, making the preparation closer to natural crystal structure and performance The bionic bone material of apatite is expected to have certain guiding significance in clinical application and development.

TB34

A

1001-3660(2022)10-0143-12

10.16490/j.cnki.issn.1001-3660.2022.10.014

2021–08–03；

2021–11–08

2021-08-03；

2021-11-08

遼寧省教育廳項目（LJ2020JCL033）

Liaoning Provincial Department of Education Project (LJ2020JCL033)

劉瑩（1970—），男，碩士，教授，主要研究方向為生物化學及天然高分子材料。

LIU Ying (1970-), Male, Master, Professor, Research focus: biochemistry and natural polymer materials.

劉瑩, 楊瑞, 劉井來, 等. 單相、雙相及多相離子摻雜的羥基磷灰石研究進展[J]. 表面技術, 2022, 51(10): 143-154.

LIU Ying, YANG Rui, LIU Jing-lai, et al. Hydroxyapatite Nanomaterials Doped with Single-phase, Dual-phase and Multiphase Ions[J]. Surface Technology, 2022, 51(10): 143-154.