等离子改性可降解镁合金的体内外降解机制及其力学和生物学行为

Patients with complicated bone fracture are commonly treated by surgical intervention. These implants are no longer useful to the patients after bone healing. If left inside the human body, they may result in stress-shielding and bone loss around the implant, and also increase the rate of post-operation infection and implant failure at the bone-implant junction. Sometimes patients are advised to undergo implant removal once the bone has healed. However, repeated surgery for implant removal will add costs to the health care system and increase morbidity to the patients. The development of biodegradable materials is therefore a desirable advancement. Among various biodegradable materials, metallic materials such as magnesium alloys are still preferable for orthopaedic implantation, as the mechanical properties of these alloys are closer to the human bone. The major obstacles to their use are their rapid degradation inside the human body, and hydrogen gas release upon degradation. Our previous work has demonstrated that the plasma immersion ion implantation (PIII) surface treatment is a feasible way to enhance the corrosion resistance of magnesium alloys, with a 4-fold increase in the anti-corrosion properties. However, little information is known about the degradation mechanism of modified surface, mechanical and biomechanical integrity of these PIII treated magnesium alloys, the cyto-toxic effects of released ions, and hydrogen gas release under in-vivo conditions. The present proposal aims to investigate and understand the degradation mechanism of plasma modified magnesium alloy thru mechanical, biomechanical, short term and long term in-vitro and in-vivo studies. If the mechanism and its influence to cellular behaviors can be thoroughly investigated,this will definitely help streamline the plasma coating in order to obtain an advanced surface modified magnesium alloys for orthoopaedic implantation.

骨折病人通常需要手术治疗，通过植入硬组织材料来辅助受伤组织的生长和愈合。然而组织愈合后，需要二次手术取出植入体，否则留在体内的植入体极易产生应力遮挡效应，导致骨骼强度降低，骨量流失，严重的会引起术后感染甚至植入失败。然而二次手术不仅增加了医疗成本，而且给病人带来很多痛苦，因此可降解生物材料的开发具有重要意义。在众多可降解材料中镁合金的力学性能接近人体骨，更适用于骨科植入，然而在人体中的快速降解限制了其临床应用。此前我们采用水等离子浸没离子注入方法有效地提高了镁合金的耐蚀性，但改性镁合金的降解机制和体内外生物医学特性尚不清楚。本项目拟通过对不同腐蚀阶段水等离子浸没离子注入处理镁合金的微观结构、生物力学、长短期及体内外生物学性能进行研究，深入探讨等离子改性镁合金的降解机制，评估其临床应用的可行性。如能达到预期结果，将为骨科植入体的发展与临床应用提供重要科学依据。

镁合金在生理环境下的腐蚀速度过快是限制其临床应用的主要原因，基于此，我们寻求一种有效的涂层保护来控制镁的降解。钛合金表面能自发形成稳定的二氧化钛钝化层保护基体，因而钛合金的耐蚀性能较好。受此现象的启发，我们采用等离子体浸没离子注入（PIII）技术在可降解镁合金表面构建二氧化钛纳米层，以减缓腐蚀环境对基体的侵蚀，解决镁合金腐蚀过快的问题。这种钛和氧PIII处理后的二氧化钛纳米层与基体镁合金无明显界面，不会由于涂层与基体合金结合差而产生保护涂层剥落的问题。此外，我们构建的二氧化钛纳米层只改变基体合金近表面的力学性能而不会影响基体的力学性能。项目研究结果表明，我们构建的二氧化钛纳米层不仅能使镁合金在动态腐蚀和静态腐蚀下均能显著提高其耐蚀性能，而且能通过抑制镁离子的快速溶出以及减少基体降解过程中的析氢而提高体外成骨细胞的活性，改善其骨传导性。.根据XPS和XRD结果可知，钛和氧PIII处理得到的二氧化钛纳米层表面平整光滑，厚度约为120nm，其主要成分是锐钛矿型二氧化钛和氧化镁。该纳米层不仅能阻隔腐蚀介质的侵蚀而且能有效调控局部微环境镁离子的溶出。伴随着镁离子的稳定溶出，MC3T3-E1前成骨细胞的黏附，活性，增殖以及分化均显著增强。此外，PIII处理镁合金组中与成骨分化密切相关的基因（ALP, Col I, Runx2 和 OPN）表达也呈现上调。在大鼠股骨末端外上踝骨缺损模型中，PIII处理镁合金组在术后十二周植入物周边新骨骨量增加175%，远远高于纯钛阳性对照组（97%）和未处理镁合金组(29%)。新骨的骨小梁厚度和骨密度也显著高于纯钛组和未处理镁合金组。组织学分析和力学测试表明PIII处理组新骨矿化良好，可以达到周边成熟骨82%的力学强度。在大鼠股骨髓内腔骨缺损模型中，未处理镁组在术后两周出现严重的免疫排斥反应，导致植入物周边出现强烈的骨吸收现象。PIII处理组在术后八周后植入物周边出现大量新骨，其骨量增加116.3%。而且新骨矿化良好与植入物结合紧密，表现出优越的骨整合和骨传导能力。总之，本项目研究成果为钛和氧PIII处理的镁合金在骨科临床应用的可行性提供了初步的实验依据。