复合SPIO的磁性根形支架对牙槽嵴位点保存骨再生影响的研究

The functional and aesthetic reconstruction after dental implantation depends on the preservation of alveolar ridge dimensions and bone regeneration in the defect. Ideal scaffolds for alveolar ridge preservation (ARP) should retain the dimensions, while enhance the bone regeneration at the same time. This project focuses on developing customized tooth root shape scaffolds by three-dimensional (3D) printing for ARP. Superparamagnetic iron oxide (SPIO) nanoparticles were added to the scaffolds to enhance the osteogenesis. And the composite scaffolds containing SPIO can be imaged by magnetic resonance imaging (MRI). To fabricate the scaffolds, coated SPIO was dispersed uniformly in the solution of biodegradable polymers. The scaffolds are 3D printed by the blends of the two. Its architecture follows digital model whose outer shape is exactly like the tooth root to be extracted, with specially designed inner structure. The effects of pore size and SPIO content to the as fabricated scaffolds were explored. Characterization including scanning electron microscope (SEM) observation, mechanical test, and in vitro degradation properties are investigated. Cell experiments are adopted to evaluate the effects on cytotoxicity, cell adhesion, proliferation and differentiation. And the mRNA levels of proteins related to osteogenesis and angiogenesis are measured. In vivo tests on animal models are characterized by micro CT and histomorphology to evaluate the quality and quantity of new bone formation. Also, dimensional preservation of alveolar ridge is evaluated. Furthermore, MRI is used to track the scaffolds degradation in vivo. The results would offer new sights in designing biomaterials for ARP, and provide new methods to characterize the degradation of scaffolds in vivo.

拔牙后牙槽窝软硬组织的充分保留以及拔牙窝内新生骨的质量对种植修复后良好功能和美观的重建非常重要。位点保存的理想支架既要维持软硬组织形态，又要有效促进牙槽窝内的骨再生。本项目旨在以复合超顺磁性氧化铁（SPIO）纳米颗粒的根形支架用于位点保存。SPIO既可促进成骨，又可使支架在MRI下显影。首先将表面处理后的SPIO均匀分散在生物可降解聚合物中进行低温三维打印得到个体化磁性根形支架。研究支架孔隙和SPIO添加量对支架性能的影响。对支架进行形貌表征、机械性能和降解性能等检测，并进行细胞实验和动物实验，检测支架的细胞毒性，对细胞黏附、增殖和分化的影响，对细胞成骨和成血管相关蛋白mRNA表达的影响；将支架植入动物拔牙创，通过micro CT和组织学手段，评价新生骨的质量和位点保存效果，并利用MRI检测支架在体内的降解。研究结果有望为位点保存支架的制备提供新思路，也为无创性监测支架降解提供一种新方法。

拔牙后牙槽窝软硬组织的充分保留以及拔牙窝内新生骨的质量对种植修复后良好功能和美观的重建非常重要。位点保存的理想支架既要维持软硬组织形态，又要有效促进牙槽窝内的骨再生。本项目旨在以复合超顺磁性氧化铁（SPIO）纳米颗粒的生物可降解支架用于骨再生和位点保存。SPIO既可促进成骨，又可使支架在MRI下显影。首先将表面处理后的SPIO添加到不同生物可降解材料中，通过先进的加工工艺包括静电纺丝法和三维打印法制备成复合SPIO的组织工程支架，对复合支架进行形貌表征、机械性能和降解性能等检测。发现SPIO的加入显著提高了支架的亲水性和机械强度。以脂肪间充质干细胞为种子细胞进行体外细胞实验，检测支架的细胞毒性，对细胞黏附、增殖和分化的影响，发现SPIO的加入同时显著促进了细胞黏附，对细胞增殖无不良影响，但是显著促进了细胞的成骨方向分化。复合支架的主要促进效应主要来自于：增强的亲水性，增大的表面面积，增强的基底刚度，接触纳米粒子并吞噬，以及磁性纳米粒子的磁效应。磁性纳米材料独特的磁学效应可对细胞成骨分化和骨修复产生更加增强的促进效应。以大鼠下切牙拔牙创为骨缺损模型，将明胶海绵负载的磁性纳米铁植入大鼠下颌中切牙拔牙窝中，以明胶海绵和拔牙后不处理的牙槽窝为对照组，观察其成骨效果。同时，测量、比较了实验组和对照组大鼠牙槽嵴长度在拔牙后的变化，以评价其对于位点保存的效果。通过micro CT和组织学手段，评价新生骨的质量和位点保存效果，并利用MRI检测支架在体内的降解。通过检测我们发现，micro CT和组织学检测结果均显示SPIO组的成骨数量和质量均好于对照组，牙槽嵴长度的萎缩小于对照组。追踪的MRI的影像是支架降解伴随新骨再生在骨缺损处的综合表现。复合SPIO组和对照组相比，在不同时间点的表现不同。因此认为，应用SPIO可以取得良好的成骨效果，最终达到良好的位点保存效果。将含SPIO支架植入动物拔牙创，研究结果有望为位点保存支架的制备提供新思路，也为无创性监测支架降解提供一种新方法。