Bioactive Hydroxyapatite Whisker Composite Ceramic Bone Substitutes

生物活性羟基磷灰石晶须复合陶瓷骨替代品

• 批准号: 0074439
• 负责人: Melissa Baumann
• 金额: $ 36.73万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-15 至 2004-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0074439&HistoricalAwards=false
• 关键词: Bioactive; Hydroxyapatite; Whisker; Composite; Ceramic

0074439CrimpThe objective of this research project is to create a novel, synthetic, biocompatible osteogenic bone substitute having mechanical properties similar to cortical bone. Every year in the U.S. alone, approximately 100,000 bone grafts are performed. Applications for bone substitutes include massive bone loss from neoplasia, comminuted fracture repair, spinal surgery, and fracture treatment in the elderly. The model bone substitute is 1) osteogenic (direct bone formation via transplanted live bone cells called osteoblasts), 2) osteoinductive (the ability to recruit bone forming cells), 3) osteoconductive (the scaffold supports bone in-growth), 4) mechanically stable (able to carry the load of the natural bone) and 5) readily available. Both the limited supply and diminished properties of autografts and allografts have led researchers on a quest for an optimum synthetic bone substitute. Because the mineral content of bone has a composition and crystal structure closely matching hydroxyapatite (HA), it is natural to first turn to bioceramics such as HA-based materials for bone implants. While dense bioceramics do not exhibit osteogenic or osteoinductive properties, HA is osteoconductive. When using HA, the surgeon is faced with a trade-off between the mechanical strength provided by dense ceramics, and the biological incorporation (bone in-growth) provided by porous ceramics. The lack of mechanical strength in combination with the ability to support bone in-growth has prevented HA, or any other bioceramic, from receiving wide spread acceptance as a cancellous or a cortical bone substitute. The research project uses Professor Crimp's background in ceramic processing to create a strong, yet porous HA-based bone substitute where osteogenic and osteoinductive properties are added by in vitro culture of these synthetic bone scaffolds with osteoblasts following protocols developed by the co-PI, Professor McCabe. HA whisker reinforced porous HA and biphasic calcium phosphate (BCP) ceramics will be fabricated using a modified foaming technique. BCP is a mixture of HA and beta-tri-calcium phosphate and is currently receiving attention as a potential bone substitute material. Of fundamental significance is the understanding of the linkages between bioceramic processing and the in vivo behavior by looking at osteoblast adhesion in vitro.This research project will concentrate on tailoring the processing protocol for whisker reinforced ceramic materials for use as bone replacements to yield improvements in strength, at a fixed porosity level matching that of human cortical bone, while maintaining the inherent biocompatibility of the implant materials. These implants will be the only viable synthetic alternative (because of improved mechanical and osteogenic properties) to currently available graft materials for repair of damaged cortical bone tissue.

0074439卷曲本研究项目的目的是创造一种新型的、合成的、生物相容的成骨骨替代物，其具有与皮质骨相似的机械性能。 仅在美国，每年就有大约10万例骨移植手术。 骨替代物的应用包括肿瘤、粉碎性骨折修复、脊柱手术和老年人骨折治疗引起的大量骨丢失。 模型骨替代物是1）成骨的（通过移植的活骨细胞（称为成骨细胞）直接骨形成），2）骨诱导的（募集骨形成细胞的能力），3）骨传导的（支架支持骨向内生长），4）机械稳定的（能够承载天然骨的负荷）和5）容易获得。 自体移植物和同种异体移植物的有限供应和降低的性能使得研究人员寻求最佳的合成骨替代物。 因为骨的矿物质含量具有与羟基磷灰石（HA）紧密匹配的组成和晶体结构，所以首先转向生物陶瓷如HA基材料用于骨植入物是自然的。 虽然致密生物陶瓷不表现出成骨或骨诱导特性，但HA具有骨传导性。 当使用HA时，外科医生面临着致密陶瓷提供的机械强度和多孔陶瓷提供的生物结合（骨长入）之间的权衡。 缺乏机械强度以及支持骨向内生长的能力阻碍了HA或任何其他生物陶瓷作为松质骨或皮质骨替代物得到广泛接受。 该研究项目使用Crimp教授在陶瓷加工方面的背景来创建一种坚固但多孔的HA基骨替代品，其中通过体外培养这些合成骨支架与成骨细胞，按照共同PI McCabe教授开发的方案，增加了成骨和骨诱导特性。 采用改进的发泡技术制备了HA晶须增强多孔HA和双相磷酸钙（BCP）陶瓷。BCP是HA和β-磷酸三钙的混合物，目前作为潜在的骨替代材料受到关注。通过观察成骨细胞在体外的粘附，了解生物陶瓷加工与体内行为之间的联系具有根本意义。本研究项目将集中于定制用于骨替代物的晶须增强陶瓷材料的加工方案，以在与人皮质骨相匹配的固定孔隙率水平下提高强度，同时保持植入材料的固有生物相容性。 这些植入物将是唯一可行的合成替代品（由于改善的机械和成骨性能），以目前可用的移植材料修复受损的皮质骨组织。