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，但我们仍然远离植入物的梦想，该植入物替代大的骨缺损并缓慢降解以将患者身体产生的新骨留在原位。这是本计划的长期目标，同时详细了解骨矿化的过程。为了实现这一目标，我的研究团队将合成和表征由可生物降解的聚合物基质和生物活性玻璃（BG）制成的生物活性支架。聚合物基质确保植入物的机械稳定性，BG促进羟基碳酸磷灰石（HCA，骨的无机成分）沉淀和植入物周围的骨再生。 我们将在越来越复杂的模拟体液（SBF）中测试支架，从仅再现体液离子成分的溶液开始，然后添加蛋白质，最后添加细胞。我们的研究结果将提供生物材料的体外和体内反应性之间的联系，这是目前缺少的，并揭示了正在进行的辩论，关于SBF更好地代表体内发生的现象。 我们将使用一系列光谱、量热和显微镜技术来分析支架表面和体液之间界面处发生的变化。这是一个关键区域，决定了机械稳定性和植入物在体内的整合。 最后，我们将用寡肽功能化支架表面，增强细胞粘附或促进HCA沉淀，目的是植入支架，而无需预先接种外部干细胞或成骨细胞，因为患者自己的细胞将被这些生物学线索吸引。 这项研究计划的成功实现将提供下一代生物活性支架，阐明它们周围的骨矿化过程，开发表面敏感技术来测试它们在SBF中的反应性，并提供有关SBF的必要指南，用于预测生物材料在体内的行为。

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.