可降解型高生物活性微晶玻璃基椎间融合器材料的设计、构建及原位组织再生研究

Spinal degenerative disease is a major disease in the middle-aged and elderly population which can lead to chronic low back pain and functional disability. Interbody fusion procedure is accepted as the gold stardand treatment for those severe cases. However, autograft which is frequently used during the operations may result in some slight but consistent symptoms in the donor site. In addition, synthetic interbody cages can not reach the optimal goal for fully regenerating a new interface in the host tissues, owing to the mismatch between high elastic modulus of the materials of titanium alloy and A-W glass-ceremics and low toughness of the bone tissues. For these reasons, it is still a great challenge to design highly bioactive and biodegradable interbody spinal fusion implants which can enhance rapid regeneration in situ of new bone tissues, and can be fully biodegraded as well after bony fusion is achieved. Our study aims to develop a new bioactive glass-ceramics(BGC)-based porous material for the operative treatment of spinal degenerative diseases. To determine if the new artifical implants could be bioactive and bioresorbable in physiological environment, the porous BGCs were fisrtly fabricated by low temperature co-sintering the composite of the sol-gel-derived boron-rich nanoscale bioactive glass (BG) and the sintering-derived microscale 45S5 BG. Furthermore, the counterionic biomacromolecules (e.g., chitosan, hyaluronic acid) were coated the wall struts of porous BGCs via a lay-by-layer assembly technique. The mechanical and physicochemical properties such as compressive strength, toughness and bioactive ion release behavior were stdudied and optimized according to relevant technique paramenters. Finally, the optimized porous BGC-based discs with improved mechanical and biological properties were implanted into the interverbral injury of beagle models, to evaluate the efficacy of fusion and new disc regeneration in situ when compared to conventional disc implants. These studies, on one hand, may explore and elucidate the underlying mechanism of mechanical reinforcement of low-melt-temperature boron-rich BG on 45S5 BG at a rather low sintering temperature condition, and other other hand, understand the toughness imporvement of the electrostatic interaction between the inorganic-organic interface and the fracture mechanism of the BGC-based porous composite biomaterials. Thus by engineering the nanostructured inorganic BG and organic biomolecules, it is possible to recreate an anatomical, structural, and histological framework, which leads to the regeneration of large, hollow tissue gaps between the chronically degenerative vertebrae.

脊柱退行性疾病是骨科常见病，椎间融合为手术金标准。术中自体骨移植造成新的创伤，钛合金和A-W玻璃陶瓷等材料与脊柱骨模量不匹配，难以达到快速融合并逐渐被宿主组织替代的理想效果，因此研究促进椎间组织再生的可降解型高生物活性材料是解决这类问题的根本途径。本项目利用低温助烧结增强协同生物分子层-层组装修饰增韧技术，以含硼生物玻璃纳米粒摻杂高生物活性生物玻璃，运用低温烧结制备一种降解性优良的微晶玻璃多孔支架，并以异性荷电生物分子交替修饰支架孔道内壁实现增强、增韧，利用比格犬腰椎损伤模型分析该新型多孔复合材料的原位促骨组织再生特性；揭示低熔点生物玻璃纳米粒低温助烧结过程微晶析出机制和晶相组成的调控途径，阐明低温助烧结增强、生物分子层-层修饰增韧的优化技术方案，明确多孔材料降解离子产物组合物调节细胞活性和促进组织再生的基本规律，全面验证材料设计的可靠性和科学性，为新一代人工椎间融合材料研究奠定理论基础。

随着我国人口老龄化的加快，各种脊柱退行性疾病日益增多，椎间融合器复合自体骨移植是手术金标准。目前常用的由钛合金和A-W玻璃陶瓷等制备的融合器与脊柱骨模量不匹配，难以达到快速融合并逐渐被宿主组织替代的理想效果，研究促进椎间组织再生的可降解型高生物活性材料是解决这类问题的根本途径。.本项目以含硼生物玻璃纳米粒掺杂高生物活性生物玻璃，利用低温助烧结增强技术，实现了微晶玻璃多孔支的增强、增韧，随后利用兔、犬等动物的临界骨缺损模型及腰椎融合模型系统分析了该类新型多孔复合材料的原位促骨组织再生特性。首先通过熔融法制备了掺氧化硼45S5生物玻璃，并在820℃～900℃下进行烧结，获得了在机械性能和生物活性等方面的改进。然后以溶胶凝胶法制备了低熔点含硼锌生物玻璃(BG-ZB)，分别在凝胶、粉末两种状态下掺入到45S5生物玻璃中，探究了不同BG-ZB掺杂方式对于煅烧后支架的机械性能和生物活性的影响。接着以此低熔点BG-ZB共掺杂制备出一类力学增强型多孔生物玻璃支架，对其机械性能、孔道结构进行了研究，并在兔股骨远端缺损模型中验证了其优良的促成骨活性及生物降解性。最后以低熔点掺硼生物玻璃（BG）的复合来强化由硅酸钙（CSi）、镁黄长石（AKE）等陶瓷材料制备的3D打印多孔支架，该类支架在具备良好贯通孔道的同时拥有较强的力学强度，应用于兔腰椎间融合模型后发现在其在骨修复的过程中能长期保持结构的稳定并促进新生骨质的长入和重建。.本项目揭示了低熔点生物玻璃纳米粒低温助烧结过程微晶析出机制和晶相组成的调控途径，阐明了低温助烧结增强、增韧的优化技术方案，明确了多孔材料降解离子产物组合物调节细胞活性和促进骨组织再生的基本规律，为新一代人工椎间融合材料研究奠定理论基础。以本项目研究成果为基础，发表了SCI收录学术论文16篇，其中SCI收录13篇；参与国际、国内学术会议13人次；培养研究生6人。