Ceramic scaffolds with engineered topography and chemistry

具有工程形貌和化学特性的陶瓷支架

• 批准号: 8019583
• 负责人: Isabelle L Denry
• 金额: $ 5.03万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2011-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8019583
• 关键词: 3-Dimensional; Acids; Address; Aging; Apatites; Architecture; Bone Regeneration; Bone Resorption; Bone Tissue; Bone Transplantation; Bone remodeling; Cadaver; Calvaria; Ceramics; Characteristics; Chemicals; Chemistry; Complex; Compressive Strength; Crystallization; Defect; Development; Engineering; Ensure; Exhibits; Glass; Goals; Gold; Harvest; Histopathology; In Vitro; Ion Exchange; Kinetics; Lead; Macor; Measures; Mechanics; Modeling; Morbidity - disease rate; Nanotopography; Niobium; Operative Surgical Procedures; Osteogenesis; Oxides; Patients; Phase; Polymers; Porifera; Porosity; Process; Property; Rattus; Replica Techniques; Research; Risk; Schedule; Site; Solubility; Strontium; Structure; Surface; Testing; X-Ray Computed Tomography; base; bone; chemical property; density; design; disease transmission; fluorapatite; in vivo; lead oxide; nanosized; novel; public health relevance; scaffold

DESCRIPTION (provided by applicant): The research proposed in this application is directed at developing novel ceramic scaffolds that are bioresorbable, bioactive, osteoconductive and exhibit high strength. These goals will be achieved through stepwise engineering of the ceramic microstructure, scaffold architecture, micro and nanotopography and surface chemistry. The rationale is that there is currently no synthetic scaffold material that is bioactive, resorbable and exhibits biologically compatible compressive strength. We will first investigate the crystallization kinetics and mechanical properties of sintered niobium- doped fluorapatite (FAp) ceramics with the aim of developing a highly crystalline ceramic with nanosized FAp crystals (Aim 1). We will select the best composition with niobium additions that will induce phase separation, lead to the crystallization of nanosized crystals and high crystallinity. We will then prepare FAp ceramic scaffolds using a carefully engineered approach that combines a pre-coating step, a glazing step and a chemical etching step (Aim 2). We postulate that optimization of the scaffold architecture will lead to superior mechanical properties and that the chemical etching step will promote a complex three-dimensional surface micro and nanotopography later stimulating contact osteogenesis. The effect of ion-exchange on surface chemistry, solubility and bioactivity of the scaffolds will be tested in Aim 3. The overall rationale is that strontium substitution in the apatite structure will increase solubility and bioactivity. Finally, the resorption and bone regeneration ability of the scaffolds will be tested in vivo using a rat calvarial critical defect model and a combination of state of the art in vivo micro-computed tomography and histopathology (Aim 4). The hypotheses tested are that the surface chemistry and topography of the scaffolds will enhance bone regeneration and that the resorption rate will be compatible with the rate of bone regeneration. PUBLIC HEALTH RELEVANCE: There is currently no ideal bone graft substitute. Autogenous bone is still considered the gold standard despite its associated morbidity. There is currently no synthetic material that is bioactive, available as a 3D-scaffold with mechanical integrity, exhibits nanotopography and is resorbable at a controlled rate. We plan to develop a synthetic ceramic scaffold that will (i) eliminate the need for a second surgical site to harvest autogenous bone, (ii) address patients concerns about the use of cadaver bone tissue and risk of disease transmission, (iii) offer superior mechanical properties compared to currently available synthetic scaffold materials (iv) promote osteoconduction and contact osteogenesis through engineered surface topography, (v) exhibit a controlled resorption rate compatible with bone regeneration rates via engineered surface chemistry, and (vi) assist in the management of congenital and acquired bony defects.

描述（由申请人提供）：本申请中提出的研究旨在开发具有生物可吸收性、生物活性、骨传导性和高强度的新型陶瓷支架。这些目标将通过陶瓷微观结构、支架结构、微米和纳米形貌以及表面化学的逐步工程来实现。其基本原理是，目前还没有具有生物活性、可吸收性且具有生物相容性抗压强度的合成支架材料。我们将首先研究烧结铌掺杂氟磷灰石（FAp）陶瓷的结晶动力学和机械性能，目的是开发具有纳米级 FAp 晶体的高结晶陶瓷（目标 1）。我们将选择添加铌的最佳组合物，这会引起相分离，导致纳米晶体的结晶和高结晶度。然后，我们将使用精心设计的方法制备 FAp 陶瓷支架，该方法结合了预涂层步骤、上光步骤和化学蚀刻步骤（目标 2）。我们假设支架结构的优化将带来优异的机械性能，并且化学蚀刻步骤将促进复杂的三维表面微米和纳米形貌，随后刺激接触成骨。离子交换对支架表面化学、溶解度和生物活性的影响将在目标 3 中进行测试。总体原理是磷灰石结构中的锶取代将增加溶解度和生物活性。最后，将使用大鼠颅骨严重缺损模型并结合最先进的体内微计算机断层扫描和组织病理学（目标 4）在体内测试支架的吸收和骨再生能力。测试的假设是支架的表面化学和形貌将增强骨再生，并且吸收率将与骨再生率相一致。 公众健康相关性：目前还没有理想的骨移植替代品。尽管存在相关的发病率，自体骨仍然被认为是黄金标准。目前还没有一种合成材料具有生物活性、可用作具有机械完整性的 3D 支架、表现出纳米形貌并且能够以受控速率再吸收。我们计划开发一种合成陶瓷支架，该支架将（i）消除对第二个手术部位获取自体骨的需要，（ii）解决患者对尸体骨组织的使用和疾病传播风险的担忧，（iii）提供优越的与目前可用的合成支架材料相比，其具有机械性能（iv）通过工程表面形貌促进骨传导和接触成骨，（v）通过工程表面化学表现出与骨再生速率相一致的受控吸收速率，以及（vi）协助管理先天性骨损伤和获得性骨缺损。