Ceramic scaffolds with engineered topography and chemistry

描述(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、生物活性、骨传导和高强度的新型陶瓷支架。这些目标将通过陶瓷微结构、支架结构、微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，目前还没有一种具有生物活性、可吸收和具有生物相容性的抗压强度的合成支架材料。我们将首先研究掺Nb氟磷灰石(FAP)陶瓷的晶化动力学和力学性能，目的是开发一种具有纳米FAP晶体的高结晶度陶瓷(目标1)。我们将选择添加Nb的最佳成分，以诱导相分离，导致纳米晶体的结晶和高结晶度。然后，我们将使用一种精心设计的方法来制备FAP陶瓷支架，该方法结合了预涂覆步骤、上釉步骤和化学蚀刻步骤(目标2)。我们推测，支架结构的优化将导致优异的力学性能，化学蚀刻步骤将促进复杂的三维表面微和纳米形貌，随后刺激接触性成骨。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，锶在磷灰石结构中的替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和体内最先进的显微计算机断层扫描和组织病理学相结合的方法，在体内测试支架的吸收和骨再生能力(Aim 4)。被测试的假设是支架的表面化学和表面形貌将促进骨再生，并且吸收率将与骨再生的速率相一致。

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.