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

由含中间氧化物的玻璃和支化聚羧酸盐制成的具有定制溶解度的骨水泥

基本信息

批准号：
271153954
负责人：
Professorin Dr. Delia Brauer
金额：
--
依托单位：
Institut für Organische Chemie und Makromolekulare Chemie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2015
资助国家：
德国
起止时间：
2014-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/271153954?language=en
关键词：
Bone cements tailored solubility intermediate

项目摘要

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.

骨水泥用作骨填充物。用于椎体或脊柱后凸成形术或锚定植入物(如：髋关节植入物)植入骨头。目前的材料包括丙烯酸(如。聚甲基丙烯酸甲酯（PMMA）或磷酸钙（CaP）水泥。然而，这两种方法都有一些缺点，例如放热固化反应（破坏周围组织），与骨骼缺乏化学键合（仅通过机械联锁粘附），PMMA胶合剂缺乏生物活性（在纤维组织中包封而不是与骨骼结合），或者CaP胶合剂的机械性能差（仅允许在非承重应用中使用）。此外，特别是对于骨填充应用，可吸收材料的使用将是非常有趣的，因为它允许骨再生而不是骨置换。虽然CaP水泥可以根据其成分被吸收，但PMMA水泥是长期稳定的。玻璃离聚体水泥（由酸可降解玻璃和聚合酸之间的中和反应形成）通常用于牙科，具有优异的机械性能，并与硬组织（牙齿和骨骼）或外科金属形成化学键。然而，从这些水泥中释放铝离子限制了它们在骨科中的应用，并且由于对玻璃酸降解机制的了解不足，以及需要合适的聚羧酸盐来形成机械稳定但可吸收的水泥，因此到目前为止，无铝替代品的开发已经失败。该项目的目的是合成和表征基于无铝、酸可降解玻璃和分支、部分可吸收聚羧酸盐的新型骨水泥，根据其机械性能（抗压强度、杨氏模量、与金属和骨骼的粘附性），适用于非承重（也可能是承重）应用。这将通过合成含中间氧化物（主要是MgO）的无铝玻璃和研究它们在相关pH条件下（pH 1-8）的溶解度来实现。特别强调的是深入了解玻璃成分、结构和溶解度之间的关系，以便预测和调整玻璃在相关pH条件下的稳定性。关于靶向骨水泥的聚合成分，我们使用自由基聚合技术合成了新型的高支化聚羧酸酯。我们将通过甲基丙烯酸/衣康酸作为共聚单体的不同比例来控制羧基的数量，而分支的程度和链间距离可以通过不同类型和数量的合适交联剂来控制。此外，我们将合成一种基于乙醇酸的可降解交联剂，为骨水泥在生理条件下提供可控制的降解特性。后者将为完全可吸收骨水泥铺平道路。