高强度骨修复支架材料的仿生可控构筑及降解速率的调控

Construction of chitosan scaffolds with symmetrical ordered structure and uniformly distributed pores via bionic structure of bone, which is assembled under different pH value, based on the in-situ precipitation method established by our group. Micro environment for bone tissue regeneration could be adapted by controlling the microstructure of material. Hydroxyapatite will be mineralized on the chitosan-based template with bionic bone structure, thus nano- hydroxyapatite could be orderly gradiently distributed in the citosan scaffolds, endowing the scaffolds with excellent biocompatibility, bone growth inductivity and bone growth guiding properties, and accelerating bone tissue regeneration. Matching the degradation rate of the scaffolds and regeneration rate of new bone could be achieved by controlling the degree of deacetylation and molecular weight of chitosan, and controlling the content, size, distribution mode and packing density of hydroxyapatite. Tracing the whole process of preparation, degradation of scaffolds by fluorescent labeling technology. Establishing a technology for building three-dimensional ordered and structure-controlled scaffold with high mechanical properties, which should be an ideal implant material for clinical bone repair.

以壳聚糖为原料，采用仿生物骨结构的设计，将三种对称有序的结构（纵向同心圆柱状层状叠加结构，横向同心辐射条状结构，辐射条以双螺旋结构堆砌结构）巧妙地融合为一体，以原位沉析法、冷冻爆破法，构建出高强度的仿骨结构支架材料。以材料微结构的控制来提高适合骨组织再生的微环境，并在仿骨结构的壳聚糖基模板上进行羟基磷灰石的仿生矿化，使得纳米羟基磷灰石在壳聚糖基骨架材料上呈梯度有序分布，赋予支架材料与骨细胞和骨组织具有更好的生物相容性和骨生长诱导性和引导性，快速促进骨修复。通过控制壳聚糖的脱乙酰度和分子量，控制羟基磷灰石的含量、粒径的大小、分布方式和堆积密度进行调控支架材料的降解速率与新骨再生速率的匹配；以荧光标记壳聚糖示踪支架材料的制备、结构形成和降解过程。通过本项目的研究，获得一种结构可控、降解速率可调、机械强度高、生物相容性好，能快速促进骨缺损修复的支架材料，以满足临床应用要求。

本项目采用原位沉析法和电场诱导法，制备了具有仿生物骨结构的壳聚糖/羟基磷灰石复合支架材料，将三种对称有序的结构（纵向同心圆柱状层状叠加结构，横向同心辐射条状结构，辐射条以双螺旋结构堆砌结构）巧妙地融合为一体，制得了具有多层次结构的壳聚糖基生物材料。动物体内降解实验表明：脱乙酰度对壳聚糖的降解行为有决定性作用，脱乙酰度为50%的壳聚糖在1个月时就可以完全降解，脱乙酰度为75%的壳聚糖在12个月时严重降解，而脱乙酰度为100%的壳聚糖在8个月时依然较为稳定，在12个月时开始发生轻度降解。动物骨缺损诱导修复实验表明：壳聚糖/羟基磷灰石仿骨多孔支架材料在术后8周，可见骨缺损处已被大量纤维组织和软骨基质填充；术后12周，软骨基质消失，可见髓腔，绝大部分编织骨被成熟的板层骨组织替代，具有非常优异的诱导成骨性能，能快速促进骨缺损的修复，有望用作临床骨科材料。