Bioresorbable 2D and 3D ordered mesoporous phosphate glasses for bone tissue regeneration and drug delivery

硬组织和软组织的再生或修复代表了现代社会的主要挑战。由于预期寿命的延长，需要植入物来替换受损组织的患者数量正在增加。因此，开发新的和更有效的生物材料是一项重大的科学和人类挑战，因为它影响着全世界数百万人的日常生活。据预测，到2020年，全球生物材料市场将达到约1300亿美元。生物材料的功能随着时间的推移而发展。第一代生物材料具有纯粹的机械作用，与生理环境（例如金属）没有相互作用。最近，第二代生物材料，定义为生物活性，基于硅酸钙玻璃已经开发出来。它们的主要特征是其表面能够自发地与人体内的生理液体一起生成羟基磷灰石Ca 10（PO 4）6（OH）2的骨样层。人体细胞在这一层上生长和增殖，促进植入物和活组织之间的紧密结合。由于硅酸盐玻璃不溶于生理液体，因此需要进行后续手术以移除植入物，从而增加了患者的风险并延长了总恢复时间。此建议涉及最新一代的生物材料，也称为“第三代”。除了生物活性外，它们还显示出生物可吸收性，因为它们随着时间的推移在生理液体中反应和溶解，并且它们被再生的硬组织或软组织取代。可溶性生物可吸收材料的使用避免了二次手术的必要性。磷酸盐基玻璃与商业上使用的聚合物不同，是理想的生物可吸收材料，具有完全生物相容性，因为任何降解产物都可能导致炎症。该提案的目的是首次使用超分子化学和溶胶-凝胶的组合来设计具有高度有序的中孔结构（2-50 nm）和高纹理性质（大表面积、孔径和体积、窄孔径分布）的磷酸盐基玻璃。磷酸盐基玻璃具有有序的二维中孔通道和三维有序的立方体互连孔网络，是多功能生物材料的理想候选者，能够同时将抗菌/抗癌活性与细胞刺激和血管形成相结合，这使得它们成为两种主要临床应用的理想材料：骨科（骨针和锚钉、骨血小板、关节置换、组织固定螺钉）和药物输送（例如抗癌药物，抗微生物剂，生长因子，我将通过合成和结构/结构表征的磷酸盐玻璃与组成接近的骨头证明这种潜力（P2 O 5-CaO-Na 2 O），添加和不添加抗菌离子（Ag+/Cu 2 +/Zn 2+），然后进行溶解和生物相容性试验。

Regeneration or repair of hard and soft tissues represents a major challenge of the modern society. The number of patients that require an implant in order to replace damaged tissue is growing due to the increase of life expectancy. Therefore, the development of new and more efficient biomaterials is a great scientific and human challenge as it has an effect on the everyday life of millions of people worldwide. It has been forecasted that the global market for biomaterials will reach about $130B by 2020. The function of biomaterials has evolved with time. The first generation of biomaterials had a pure mechanical role with no interaction with the physiological environment (e.g. metals). More recently, a second generation of biomaterials, defined as bioactive, based on calcium silicate glasses has been developed. Their key feature is the capability of their surface to spontaneously with physiological fluids in the human body generating a bone-like layer of hydroxyapatite Ca10(PO4)6(OH)2. Human cells grow and proliferate on this layer promoting a tight bond between the implant and the living tissue. As silicate based glasses are non-soluble in physiological fluids, a subsequent surgery is needed to remove the implant with increased risk for the patient and a lengthening of the total recovery time.This proposal refers to the latest generation of biomaterials also called "third generation". In addition to the bioactivity, they also show bioresorbability as they react and dissolve over time in the physiological fluid and they are replaced by regenerated hard or soft tissue. The use of soluble bioresorbable materials avoids the necessity of a second surgery. Phosphate-based glasses, differently from the commercially used polymers, are ideal bioresorbable materials being totally biocompatible as any of the degradation products can cause inflammation. The aim of this proposal is to design, for the first time, phosphate-based glasses with highly ordered structure of mesopores (2-50 nm) and high textural properties (large surface area, pore size and volume, narrow pore size distribution) using a combination of supramolecular chemistry and sol-gel. Phosphate based glasses with ordered 2D channels of mesopores aligned in one direction and 3D ordered cubic network of interconnected pores are excellent candidates for multifunctional biomaterials, being able to combining simultaneously anti-bacterial/anti-cancer activity with cell stimulation and vascularisation.This makes them ideal materials to be used in two major clinical applications: orthopedics (bone pins and anchors, bone platelets, joint replacements, tissue fixation screws) and drug delivery (e.g. anticancer drugs, antimicrobial agents, growth factors, DNA).I will demonstrate this potentiality through synthesis and textural/structural characterisation of phosphate glasses with composition close to the bone (P2O5-CaO-Na2O) with and without addition of antimicrobial ions (Ag+/Cu2+/Zn2+) followed by dissolution and biocompatibility tests.