Bioactive Hydroxyapatite Whisker Composite Ceramic Bone Substitutes

本研究项目的目标是创造一种新型的、合成的、生物相容性的骨替代物，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造成的大量骨质流失、粉碎性骨折修复、脊柱手术和老年人骨折治疗。模型骨替代物是1)成骨（通过移植的活骨细胞称为成骨细胞直接形成骨），2)骨诱导（招募骨形成细胞的能力），3)骨传导（支架支持生长中的骨），4)机械稳定（能够承受天然骨的负荷），5)易于获得。自体骨和同种异体骨的有限供应和性能下降都促使研究人员寻求一种最佳的合成骨替代品。由于骨的矿物成分和晶体结构与羟基磷灰石（HA）密切匹配，因此首先转向生物陶瓷（如HA基材料）用于骨植入物是很自然的。虽然致密生物陶瓷不表现成骨或骨诱导特性，但透明质酸具有骨导电性。当使用透明质酸时，外科医生面临着在致密陶瓷提供的机械强度和多孔陶瓷提供的生物掺入（骨生长）之间进行权衡。缺乏机械强度和支持骨生长的能力阻碍了透明质酸或任何其他生物陶瓷作为松质骨或皮质骨替代品被广泛接受。该研究项目利用了Crimp教授在陶瓷加工方面的背景知识，创造了一种坚固、多孔的ha基骨替代品，通过体外培养这些合成骨支架和成骨细胞，增加了成骨和骨诱导特性，这些合成骨支架是按照共同项目负责人McCabe教授制定的方案进行的。采用改进的发泡技术制备HA晶须增强多孔HA和双相磷酸钙（BCP）陶瓷。BCP是透明质酸和β -磷酸三钙的混合物，目前作为一种潜在的骨替代材料受到关注。具有根本意义的是通过观察体外成骨细胞粘附来理解生物陶瓷加工与体内行为之间的联系。该研究项目将专注于定制用于骨替代物的晶须增强陶瓷材料的加工方案，以提高强度，在与人类皮质骨匹配的固定孔隙度水平上，同时保持植入材料固有的生物相容性。这些植入物将是目前可用的修复受损皮质骨组织的移植材料的唯一可行的合成替代材料（因为其改进的机械和成骨性能）。

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.