Ceramic scaffolds with engineered topography and chemistry

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、骨导电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、微纳米形貌和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、可吸收性和具有生物相容性抗压强度的合成支架材料。我们将首先研究掺铌氟磷灰石（FAp）陶瓷的结晶动力学和力学性能，目的是开发一种具有纳米级掺铌氟磷灰石晶体的高结晶陶瓷（aim 1）。我们将选择最佳的组合物，加入铌，诱导相分离，导致纳米级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，上釉步骤和化学蚀刻步骤（目标2）。我们假设支架结构的优化将导致优越的机械性能，化学蚀刻步骤将促进复杂的三维表面微纳米形貌，然后刺激接触成骨。离子交换对支架表面化学、溶解度和生物活性的影响将在Aim 3中进行测试。总的原理是，锶取代磷灰石结构将增加溶解度和生物活性。最后，支架的吸收和骨再生能力将通过大鼠颅骨严重缺陷模型和最先进的体内微计算机断层扫描和组织病理学相结合进行体内测试（Aim 4）。所测试的假设是，支架的表面化学和形貌会促进骨再生，并且吸收速率将与骨再生速率相适应。

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.