Bioactive scaffolds for bone regeneration: a surface science approach

尽管最近在骨科应用的生物材料方面有所改进，但我们仍远未梦想出一种植入物来替代巨大的骨缺损并慢慢降解，以保留患者身体产生的新骨。这是本项目的长期目标，同时也是对骨矿化过程的详细了解。为了实现这一目标，我的研究团队将合成并表征由可生物降解的聚合物基质和生物活性玻璃(BG)组成的生物活性支架。聚合物基质确保了植入物的机械稳定性，而BG促进了羟基碳酸盐磷灰石(HCA，骨的无机成分)的沉淀，并促进了植入物周围的骨再生。 我们将在模拟体液(SBF)中测试支架，测试的复杂性从仅复制体液离子组成的溶液开始，然后添加蛋白质，最后是细胞。我们的结果将提供生物材料的体外和体内反应性之间的联系，目前还缺乏这一联系，并揭示了正在进行的关于哪种SBF更好地代表体内发生的现象的争论。 我们将使用一系列光谱、量热和显微技术来分析支架表面和体液之间的界面上发生的变化。这是一个至关重要的区域，它决定了植入物在体内的机械稳定性和完整性。 最后，我们将用寡肽对支架表面进行功能化处理，这些寡肽可以增强细胞黏附或促进HCA沉淀，目标是植入支架，而不是预先在支架上种植外部干细胞或成骨细胞，因为患者自己的细胞会被这些生物线索吸引。 这一研究计划的成功完成将提供新一代生物活性支架，阐明其周围的骨矿化过程，开发表面敏感技术来测试其在SBF中的反应性，并为预测生物材料的体内行为提供必要的指南。

Despite recent improvement in biomaterials for orthopedic applications, we are still far from the dream of an implant that substitutes large bone defects and slowly degrades to leave in place new bone generated by the patient's body. This is the long term objective of the present program, together with a detailed understanding of the process of bone mineralization. To achieve it, my research team will synthesize and characterize bioactive scaffolds made of a biodegradable polymeric matrix and bioactive glass (BG). The polymeric matrix ensures mechanical stability to the implant and BG promotes precipitation of hydroxyl carbonate apatite (HCA, the inorganic component of bones), and bone regrowth around the implant. We will test the scaffolds in simulated body fluids (SBFs) at increasing levels of complexity, starting from solutions that reproduce only the ionic composition of body fluids, and then adding proteins and finally cells. Our results will provide a link between in-vitro and in-vivo reactivity of biomaterials, which is missing at the moment, and shed light on the ongoing debate concerning which SBF represents better the phenomena occurring in-vivo. We will use an array of spectroscopic, calorimetric and microscopic techniques to analyze the changes occurring at the interface between the scaffolds' surface and the body fluids. This is a crucial region, which determines the mechanical stability and the integration of the implant in the body. Finally, we will functionalize the surface of the scaffolds with oligopeptides that enhance cell adhesion or promote HCA precipitation, with the goal of implanting the scaffolds without pre-seeding them with external stem cells or osteoblasts, since the patient's own cells will be attracted by these biological cues. The successful achievement of this research program will deliver a next generation bioactive scaffolds, elucidate the process of bone mineralization around them, develop surface-sensitive techniques to test their reactivity in SBFs, and provide needed guidelines about SBFs useful to predict biomaterials behaviour in-vivo.