聚电解质改性自矿化胶原膜的构建及其引导骨再生的机制研究

Although collagen membranes have been clinically applied for guided bone regeneration (GBR), rapid in vivo degradation, poor mechanical properties and limited osteo-inductivity adversely afftect their clinical outcomes. Thus, the “ideal” membrane for use in GBR has yet to be developed. In our previous studies, we found that polyelectrolytes can stabilize the calcium phosphate mineralizing solution and lead to intrafibrillar mineralization in vitro, which significantly increases the mechanical properties, collagenase enzyme resistance and osteo-conductivity of collagen. Our preliminary data further showed that polyelectrolyte-bound collagen could increase the zeta potential of the collagen and induce intrafibrillar mineralization in vivo. It is hypothesized that the introduction of hydroxyapatite, increased stiffness and surface potential of the modified collagen may benefit the bone defect restoration. Nevertheless, whether the self-mineralizing strategy can be used to systematically addressing both the barrier and the bioactive properties of the GBR membrane still await elucidation. In the present study, we plan to covalently bind polyelectrolyte to collagen membrane to develop a smart self-mineralizing GBR collagen membrane that combines the clinical manageability, cell occlusion properties, space-making ability and osteo-inductivity. We will further investigate the detailed mechanism of the self-induced mineralization, the biological outcomes of the modified membrane, as well as the precise role of the membrane in guided bone regeneration. The accomplishment of this project will provide a promising strategy for the clinical application of biomimetic mineralization technique and a novel biologically active and functional GBR membrane.

空间维持能力和骨诱导能力不足是限制胶原基引导骨组织再生(GBR)膜应用效果的主要掣肘。前期研究发现纤维内仿生矿化技术可以诱导羟基磷灰石晶体在胶原纤维内部沉积，而显著提高其机械性能、耐酶解性和骨传导能力。预实验结果显示利用仿生矿化理念，在胶原膜上锚定聚电解质，可以在显著改变胶原表面电势赋予其一定电学信号的同时，在体自发诱导纤维内矿化的形成，从而有利于胶原膜持续的维持成骨空间并通过电学和机械学信号引导骨形成。但是有关影响胶原膜自矿化的具体因素及其体内引导骨再生的效果及机制仍不明确。本课题拟采用聚电解质来改性胶原膜，综合利用引导组织再生理念、纤维内仿生矿化技术和内建仿生微电场促成骨技术，形成一种兼具良好的操作性能、屏障功能、空间维持功能和成骨诱导功能的智能化GBR膜并探索改性胶原发生自矿化的机制及材料机械学信号和电学信号协同引导骨再生修复的机制，以期实现GBR膜从被动屏障到主动成骨的功能转变。

空间维持能力和骨诱导能力不足是限制胶原基引导骨组织再生（GBR）膜应用效果的主要掣肘。本课题前期研究结果表明，利用纤维内仿生矿化技术在胶原膜上锚定聚电解质，可以诱导羟基磷灰石晶体在胶原纤维内部沉积，在体自发诱导纤维内矿化的形成，显著提高胶原膜的机械性能、耐酶解性和骨传导能力。但是有关影响胶原膜自矿化的具体因素及其体内引导骨再生的效果及机制仍不明确。本课题采用材料学以及生物学等多种研究方法，综合利用引导组织再生理念和仿生矿化技术，成功研发出一种兼具良好的操作性能、屏障功能、空间维持功能和成骨诱导功能的结构功能一体化的仿生矿化胶原膜，实现了胶原膜从被动屏障到主动成骨的功能转变，为扩大GBR技术的适应症，提高其成功率提供了新的策略。同时，本课题进一步对改性胶原发生自矿化的机制，以及材料机械学信号和电学信号协同引导骨再生修复的机制进行深入探究，发现自矿化胶原膜促进小鼠骨髓间充质干细胞向成骨分化过程与线粒体的生物发生密切相关；并进一步证实自矿化胶原膜通过调控线粒体动力学平衡以及线粒体自噬促进骨髓间充质细胞向成骨细胞分化，为揭示生理性及病理性矿化的本质提供新的参考。