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: 8281742
• 负责人: Isabelle L Denry
• 金额: $ 30.78万
• 依托单位: UNIVERSITY OF IOWA
• 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 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8281742
• 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可生物可吸收，生物活性，破骨传导性和表现高强度的新型陶瓷支架。这些目标将通过对陶瓷微结构，脚手架结构，微型和纳米形态以及表面化学的逐步工程来实现。理由是目前尚无生物活性，可吸收并具有生物学兼容的抗压强度的合成支架材料。我们将首先研究烧结的Niobium掺杂的氟磷灰石（FAP）陶瓷的结晶动力学和机械性能，目的是开发带有纳米化FAP晶体的高度结晶陶瓷（AIM 1）。我们将选择最佳的组成，并添加氮化物，从而诱导相分离，导致纳米化晶体的结晶和高结晶度。然后，我们将使用精心设计的方法来准备FAP陶瓷支架，该方法结合了预涂层步骤，玻璃的步骤和化学蚀刻步骤（AIM 2）。我们假设脚手架结构的优化将导致优质的机械性能，并且化学蚀刻步骤将促进复杂的三维表面微型和纳米造影，然后刺激接触式成骨。离子交换对脚手架表面化学，溶解度和生物活性的影响将在AIM 3中进行测试。总体理由是，磷灰石结构中的锶取代将提高溶解度和生物活性。最后，脚手架的吸收和骨再生能力将在体内使用大鼠刻痕临界缺陷模型和体内微型计算机层析成像和组织病理学中的最新状态进行体内测试（AIM 4）。测试的假设是脚手架的表面化学和地形将增强骨骼再生，并且吸收率将与骨再生速率兼容。 公共卫生相关性：目前没有理想的骨移植替代品。尽管具有相关的发病率，但自体骨仍然被认为是黄金标准。目前尚无生物活性的合成材料，可作为具有机械完整性的3D型物件可用，具有纳米造影术，并且可以以受控的速率将其复原。我们计划开发一种合成的陶瓷支架，该支架将（i）消除第二个手术部位收获自动骨骼的需求，（ii）解决患者对使用尸体骨骼组织的使用和疾病传播风险的担忧，（iii）可提供优质与当前可用的合成支架材料（IV）相比，机械性能通过工程表面形象促进了骨质传导和接触式成骨，（V）表现出与工程表面化学相兼容的受控吸收率，并通过工程表面化学兼容（VI）并获得了骨缺陷。