低弹性模量仿生种植体的基础研究
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摘要
目的
研究与骨组织弹性模量相匹配的生物活性种植体，并通过一系列体内外试验评价该种植体的生物相容性、骨结合能力、生物力学相容性等特点,以及周围骨组织的力学生物学反应，从而为该种植体的临床应用提供基础研究。
方法
以近β型TLM钛合金（Ti25Nb3Zr3Mo2Sn）作为种植体的基体材料，其弹性模量约为纯钛的1/2，而力学强度高于纯钛。为了提高钛合金表面的生物活性，通过微弧氧化（MAO）水热后处理（Htt）技术，在种植体表面形成粗糙多孔并复合有纳米HA的仿生涂层，从而制备低弹性模量的仿生种植体。通过检测该涂层的表面形貌、物相结构、粗糙度、亲水性等表征涂层的理化性能；以溶血实验、细胞毒性实验、急性全身毒性实验、皮下植入试验等评价种植体的生物相容；并在Beagle犬颌骨内骨水平植入该种植体，与相同处理的纯钛种植体和光滑表面的纯钛种植体相比较，结合Raman光谱、纳米压痕、硬组织切片等手段分析该种植体骨结合的质量。进一步通过延期负重，模拟种植体口内负载的环境，与高弹性模量的相同表面处理的纯钛种植体相比较，研究力学负载条件下TLM钛合金种植体（低弹性模量）结合骨的力学生物学行为，特别是种植体颈部骨结合的骨改建，以硬组织切片、Raman光谱、纳米压痕等多学科手段定量地研究该低弹性模量仿生种植体的生物活性和生物力学相容性优势。
结果
1. TLM钛合金经过微弧氧化处理（MAO）在其表面构建与牙本质小管相似的粗糙多孔结构，结合水热后处理（Htt），在该多孔结构的基础上复合生物活性的薄层纳米HA，从而构建出与牙本质-牙骨质复合体结构相似的种植体仿生涂层。
2. TLM-MAO-Htt涂层理化性能的表征其表面粗糙度Ra为1.684μm，接触角为13.8±1.7°，亲水性大大提高；Ti-MAO-Htt涂层的表面结构、粗糙度、亲水性等与TLM-MAO-Htt涂层相似，二者间无明显区别。
3.一系列的生物相容性实验证实TLM-MAO-Htt和Ti-MAO-Htt涂层具有很好的生物相容性，并具有异位成骨能力。
4. Beagle犬颌骨内植入试验研究中，发现TLM-MAO-Htt种植体和相同处理的纯钛种植体（Ti-MAO-Htt）骨结合的效率和质量无明显差别，但二者均明显高于光滑表面的纯钛种植体(Ti-S)。
5.在种植体延期负载试验中，发现高弹性模量的Ti-MAO-Htt种植体的骨结合率、螺纹内骨的面积率、皮质骨区结合骨的弹性模量和硬度均显著低于低弹性模量的TLM-MAO-Htt种植体（P≤0.05）；而Ti-MAO-Htt种植体颈部呈角形骨吸收，种植体结合骨的骨改建较TLM-MAO-Htt种植体活跃。
结论
1.通过微弧氧化水热处理可在TLM钛合金表面成功构建粗糙多孔并复合有纳米HA的微纳米结构，与牙本质-牙骨质复合体结构相似，初步实现了牙种植体仿生涂层的构建。
2. TLM-MAO-Htt涂层具有很高的亲水性、生物相容性和生物活性。
3. TLM-MAO-Htt和Ti-MAO-Htt两组种植体的骨结合质量明显优于未处理的光滑纯钛组种植体。
4.低弹性模量的TLM-MAO-Htt种植体与高弹性模量Ti-MAO-Htt种植体相比较，低弹性模量组种植体与周围骨组织间具有更好的力学相容性。
Objective
To design study a bioactive implant that its elastic modulus matches with thebone tissue through both in vitro and in vivo tests which are able to evaluate thebiocompatibility and biomechanical compatibility of the implant, as well as themechanical biological reaction of the bone tissue around the implant so as to provide a basicstudy for the clinical application of this kind of implant.
Methods
TLM titanium alloy (Ti25Nb3Zr3Mo2Sn) which was approximate to β type wasused as the base material for the implant. Its elastic modulus is about1/2of the puretitanium while the mechanical strength is higher. In order to improve the biologicalactivity of the TLM titanium alloy surface, a biomimetic coating with rough andporous structure compounded with nano-HA was prepared via micro-arc oxidation(MAO) and hydrothermal treatment (Htt). In such a manner, two kinds of bionicimplants (TLM-MAO-Htt and Ti-MAO-Htt) were prepared. The surface morphology,phase structure, roughness and hydrophilicity of the coating were detected to characterize itsphysicochemical properties and the hemolysis experiments, cell toxicity test, acute systemictoxicity test and subcutaneous implantation test were applied to evaluate the biocompatibilityof the implants. We also embedded the TLM-MAO-Htt and Ti-MAO-Htt implants intobeagle dogs’ mandible at bone margin level and analyzed the quality of theosseointegration through Raman spectroscopy, nanoindentation, hard tissue slices analysescompared with both rough (Ti-MAO-Htt) and smooth pure titanium implant(Ti-S) with thesame processing. Delayed loading on the implants which can simulate the intraoral loadingenvironment was further carried on to study the mechanical biological behavior ofosseointegrated bone around the TLM-MAO-Htt and Ti-MAO-Htt implants, especially the osseointegration at the neck position. With multidisciplinary approaches of hard tissuesections analysis, Raman spectroscopy and nanoindentation, we quantitatively studied thebioactive and biomechanical compatible advantages of the low elastic modulus implants(TLM-MAO-Htt) compared to the high elastic modulus implants (Ti-MAO-Htt).
Results
1. TLM titanium alloy possessed a porous surface comprised of bioactive nanoHA after micro-arc oxidation (MAO) and hot water (Htt) treatment, which wassuccessfully mimicked the natural structure of dentin-cementum complex.
2. The surface roughness (Ra) of TLM-MAO-Htt coating, was1.684μm; thecontact angle was13.8±1.7°and the hydrophilicity is enhanced; meanwhile, thecoating structure, roughness, and hydrophilic of Ti-MAO-Htt surface was similar tothe TLM-MAO-Htt coating, with no significant difference.
3. The coating of TLM-MAO-Htt and Ti-MAO-Htt implants exhibited goodbiocompatibility and ectopic bone formation ability.
4. No significant differences were found in the efficiency and quality ofosseointegration between the TLM-MAO-Htt implants and Ti-MAO-Htt implants inin vivo experiment, but both were significantly higher than the Ti-S implants（P≤0.05）.
5. In the delayed loading test, we found that the osseointegration rate, percentageof bone inside the thread (BIT), the hardness and elastic modulus of cortical bonearound implants were much lower in the Ti-MAO-Htt group comparing to theTLM-MAO-Htt group （P≤0.05）. There were significant angular resorption in thecortical bone around neck of Ti-MAO-Htt implants, and the bone remodeling wassignificantly more active than TLM-MAO-Htt group.
Conclusions
1. By micro-arc oxidation and water heat operation on TLM titanium alloysurface, a rough and porous biomimetic coating with nano-HA can be successfullyconstructed, which is similar to dentin-cementum complex.
2. Our TLM-MAO-Htt coating exhibits a favorable hydrophilicity,biocompatibility and bioactivity.
3. The quality of osseointegration of TLM-MAO-Htt implants is similar toTi-MAO-Htt implants and superior to Ti-S implants.
4. Compared with high elastic modulus implants (Ti-MAO-Htt), TLM-MAO-Httimplants with low elastic modulus possess a better mechanical compatibility with thesurrounding bone.
研究与骨组织弹性模量相匹配的生物活性种植体，并通过一系列体内外试验评价该种植体的生物相容性、骨结合能力、生物力学相容性等特点,以及周围骨组织的力学生物学反应，从而为该种植体的临床应用提供基础研究。
方法
以近β型TLM钛合金（Ti25Nb3Zr3Mo2Sn）作为种植体的基体材料，其弹性模量约为纯钛的1/2，而力学强度高于纯钛。为了提高钛合金表面的生物活性，通过微弧氧化（MAO）水热后处理（Htt）技术，在种植体表面形成粗糙多孔并复合有纳米HA的仿生涂层，从而制备低弹性模量的仿生种植体。通过检测该涂层的表面形貌、物相结构、粗糙度、亲水性等表征涂层的理化性能；以溶血实验、细胞毒性实验、急性全身毒性实验、皮下植入试验等评价种植体的生物相容；并在Beagle犬颌骨内骨水平植入该种植体，与相同处理的纯钛种植体和光滑表面的纯钛种植体相比较，结合Raman光谱、纳米压痕、硬组织切片等手段分析该种植体骨结合的质量。进一步通过延期负重，模拟种植体口内负载的环境，与高弹性模量的相同表面处理的纯钛种植体相比较，研究力学负载条件下TLM钛合金种植体（低弹性模量）结合骨的力学生物学行为，特别是种植体颈部骨结合的骨改建，以硬组织切片、Raman光谱、纳米压痕等多学科手段定量地研究该低弹性模量仿生种植体的生物活性和生物力学相容性优势。
结果
1. TLM钛合金经过微弧氧化处理（MAO）在其表面构建与牙本质小管相似的粗糙多孔结构，结合水热后处理（Htt），在该多孔结构的基础上复合生物活性的薄层纳米HA，从而构建出与牙本质-牙骨质复合体结构相似的种植体仿生涂层。
2. TLM-MAO-Htt涂层理化性能的表征其表面粗糙度Ra为1.684μm，接触角为13.8±1.7°，亲水性大大提高；Ti-MAO-Htt涂层的表面结构、粗糙度、亲水性等与TLM-MAO-Htt涂层相似，二者间无明显区别。
3.一系列的生物相容性实验证实TLM-MAO-Htt和Ti-MAO-Htt涂层具有很好的生物相容性，并具有异位成骨能力。
4. Beagle犬颌骨内植入试验研究中，发现TLM-MAO-Htt种植体和相同处理的纯钛种植体（Ti-MAO-Htt）骨结合的效率和质量无明显差别，但二者均明显高于光滑表面的纯钛种植体(Ti-S)。
5.在种植体延期负载试验中，发现高弹性模量的Ti-MAO-Htt种植体的骨结合率、螺纹内骨的面积率、皮质骨区结合骨的弹性模量和硬度均显著低于低弹性模量的TLM-MAO-Htt种植体（P≤0.05）；而Ti-MAO-Htt种植体颈部呈角形骨吸收，种植体结合骨的骨改建较TLM-MAO-Htt种植体活跃。
结论
1.通过微弧氧化水热处理可在TLM钛合金表面成功构建粗糙多孔并复合有纳米HA的微纳米结构，与牙本质-牙骨质复合体结构相似，初步实现了牙种植体仿生涂层的构建。
2. TLM-MAO-Htt涂层具有很高的亲水性、生物相容性和生物活性。
3. TLM-MAO-Htt和Ti-MAO-Htt两组种植体的骨结合质量明显优于未处理的光滑纯钛组种植体。
4.低弹性模量的TLM-MAO-Htt种植体与高弹性模量Ti-MAO-Htt种植体相比较，低弹性模量组种植体与周围骨组织间具有更好的力学相容性。
Objective
To design study a bioactive implant that its elastic modulus matches with thebone tissue through both in vitro and in vivo tests which are able to evaluate thebiocompatibility and biomechanical compatibility of the implant, as well as themechanical biological reaction of the bone tissue around the implant so as to provide a basicstudy for the clinical application of this kind of implant.
Methods
TLM titanium alloy (Ti25Nb3Zr3Mo2Sn) which was approximate to β type wasused as the base material for the implant. Its elastic modulus is about1/2of the puretitanium while the mechanical strength is higher. In order to improve the biologicalactivity of the TLM titanium alloy surface, a biomimetic coating with rough andporous structure compounded with nano-HA was prepared via micro-arc oxidation(MAO) and hydrothermal treatment (Htt). In such a manner, two kinds of bionicimplants (TLM-MAO-Htt and Ti-MAO-Htt) were prepared. The surface morphology,phase structure, roughness and hydrophilicity of the coating were detected to characterize itsphysicochemical properties and the hemolysis experiments, cell toxicity test, acute systemictoxicity test and subcutaneous implantation test were applied to evaluate the biocompatibilityof the implants. We also embedded the TLM-MAO-Htt and Ti-MAO-Htt implants intobeagle dogs’ mandible at bone margin level and analyzed the quality of theosseointegration through Raman spectroscopy, nanoindentation, hard tissue slices analysescompared with both rough (Ti-MAO-Htt) and smooth pure titanium implant(Ti-S) with thesame processing. Delayed loading on the implants which can simulate the intraoral loadingenvironment was further carried on to study the mechanical biological behavior ofosseointegrated bone around the TLM-MAO-Htt and Ti-MAO-Htt implants, especially the osseointegration at the neck position. With multidisciplinary approaches of hard tissuesections analysis, Raman spectroscopy and nanoindentation, we quantitatively studied thebioactive and biomechanical compatible advantages of the low elastic modulus implants(TLM-MAO-Htt) compared to the high elastic modulus implants (Ti-MAO-Htt).
Results
1. TLM titanium alloy possessed a porous surface comprised of bioactive nanoHA after micro-arc oxidation (MAO) and hot water (Htt) treatment, which wassuccessfully mimicked the natural structure of dentin-cementum complex.
2. The surface roughness (Ra) of TLM-MAO-Htt coating, was1.684μm; thecontact angle was13.8±1.7°and the hydrophilicity is enhanced; meanwhile, thecoating structure, roughness, and hydrophilic of Ti-MAO-Htt surface was similar tothe TLM-MAO-Htt coating, with no significant difference.
3. The coating of TLM-MAO-Htt and Ti-MAO-Htt implants exhibited goodbiocompatibility and ectopic bone formation ability.
4. No significant differences were found in the efficiency and quality ofosseointegration between the TLM-MAO-Htt implants and Ti-MAO-Htt implants inin vivo experiment, but both were significantly higher than the Ti-S implants（P≤0.05）.
5. In the delayed loading test, we found that the osseointegration rate, percentageof bone inside the thread (BIT), the hardness and elastic modulus of cortical bonearound implants were much lower in the Ti-MAO-Htt group comparing to theTLM-MAO-Htt group （P≤0.05）. There were significant angular resorption in thecortical bone around neck of Ti-MAO-Htt implants, and the bone remodeling wassignificantly more active than TLM-MAO-Htt group.
Conclusions
1. By micro-arc oxidation and water heat operation on TLM titanium alloysurface, a rough and porous biomimetic coating with nano-HA can be successfullyconstructed, which is similar to dentin-cementum complex.
2. Our TLM-MAO-Htt coating exhibits a favorable hydrophilicity,biocompatibility and bioactivity.
3. The quality of osseointegration of TLM-MAO-Htt implants is similar toTi-MAO-Htt implants and superior to Ti-S implants.
4. Compared with high elastic modulus implants (Ti-MAO-Htt), TLM-MAO-Httimplants with low elastic modulus possess a better mechanical compatibility with thesurrounding bone.
引文
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