Bone cements with tailored solubility from intermediate oxide-containing glasses and branched polycarboxylates

骨水泥用作骨填充物（例如，在椎体成形术或椎体后凸成形术中）或用于锚定植入物（例如，髋关节植入物）植入骨中。目前的材料包括丙烯酸（例如，聚（甲基丙烯酸甲酯，PMMA）或磷酸钙（CaP）骨水泥。然而，两者都有几个缺点，例如放热固化反应（损伤周围组织），缺乏与骨的化学结合（仅通过机械互锁粘合）和PMMA骨水泥缺乏生物活性（包封在纤维组织中而不是与骨结合），或CaP骨水泥的机械性能差（仅允许用于非承重应用）。此外，特别是对于骨填充物应用，可吸收材料的使用将是非常令人感兴趣的，因为它允许骨再生而不是骨置换。虽然CaP骨水泥根据其成分可被吸收，但PMMA骨水泥是长期稳定的。玻璃离子水门汀（通过酸可降解玻璃和聚合酸之间的中和反应固化）通常用于牙科，显示出优异的机械性能，并与硬组织（牙齿和骨骼）或外科金属形成化学键。然而，从这些水泥中释放的铝离子限制了它们在骨科中的使用，并且由于对玻璃酸降解机制的认识不足以及需要合适的聚羧酸盐以形成机械稳定但可再吸收的水泥，因此无铝替代品的开发迄今为止失败。酸可降解的玻璃和支化的、部分可再吸收的聚羧酸酯，根据它们的机械性能（抗压强度、杨氏模量、对金属和骨的粘附性）适用于非承重（和潜在的承重）应用。这将通过合成含中间氧化物（主要是MgO）的不含Al的玻璃和研究它们在相关pH条件（pH 1-8）下的溶解度来实现。将特别强调深入了解玻璃组成，结构和溶解度之间的关系，以预测和定制相关pH条件下的玻璃稳定性。关于目标骨水泥的聚合物组分，我们使用自由基聚合技术合成新型的高度支化的聚羧酸酯。我们将通过不同比例的甲基丙烯酸/衣康酸作为（共）单体来控制羧酸基团的量，而支化度和链间距离可以通过改变合适的交联剂的类型和量来控制。此外，我们将合成一种基于乙醇酸的可降解交联剂，以提供在生理条件下具有受控降解特性的骨水泥。后者将为完全可吸收的骨水泥铺平道路。

Bone cements are used as bone fillers (eg. in vertebro- or kyphoplasty) or for anchoring implants (eg. hip implants) into the bone. Current materials include acrylic (eg. poly(methyl methacrylate, PMMA) or calcium phosphate (CaP) cements. Both have several drawbacks, however, such as exothermic setting reaction (damaging the surrounding tissue), lack of chemical bonding to bone (adhesion by mechanical interlocking only) and absence of bioactivity (encapsulation in fibrous tissue rather than bonding to bone) for PMMA cements, or poor mechanical properties (allowing for use in non-load bearing applications only) for CaP cements. In addition, particularly for bone filler applications, the use of resorbable materials would be of great interest, as it allows for bone regeneration rather than bone replacement. While CaP cements can be resorbable depending on their composition, PMMA cements are long-term stable. Glass ionomer cements (which set by a neutralisation reaction between an acid-degradable glass and a polymeric acid) are routinely used in dentistry, show excellent mechanical properties and form chemical bonds with hard tissue (teeth and bone) or surgical metals. However, the release of aluminium ions from these cements limits their use in orthopaedics, and the development of Al-free alternatives has so far failed because of poor understanding of the glass acid degradation mechanism as well as a need for suitable polycarboxylates allowing for the formation of mechanically stable but resorbable cements.The aim of this project is the synthesis and characterization of novel bone cements based on Al-free, acid-degradable glasses and branched, partly resorbable polycarboxylates suitable for use in non-load bearing (and potentially also load bearing) applications according to their mechanical properties (compressive strength, Young's modulus, adhesion to metal and bone). This will be realized via the synthesis of intermediate oxide (predominantly MgO)-containing Al-free glasses and investigations concerning their solubility under relevant pH conditions (pH 1-8). Particular emphasis will be put on gaining in-depth understanding on the relationship between glass composition, structure, and solubility in order to predict and tailor glass stability under relevant pH conditions. Regarding the polymeric component of the targeted bone cements, we synthesize novel, highly branched polycarboxylates using free radical polymerization techniques. We will control the amount of carboxylic acid groups by different ratios of methacrylic/itaconic acid as (co-)monomers, whereas the degree of branching and the inter-chain distance can be controlled by varying type and amount of a suitable crosslinker. Furthermore, we will synthesize a degradable crosslinker based on glycolic acid to provide bone cements with a controlled degradation profile under physiological conditions. The latter will pave the way towards fully resorbable bone cements.