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.
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.
|Denry, Isabelle; Goudouri, Ourania-Menti; Fredericks, Douglas C et al. (2018) Strontium-releasing fluorapatite glass-ceramic scaffolds: Structural characterization and in vivo performance. Acta Biomater 75:463-471|
|Denry, Isabelle; Goudouri, Ourania-Menti; Harless, Jeffrey D et al. (2018) Strontium-releasing fluorapatite glass-ceramics: Crystallization behavior, microstructure, and solubility. J Biomed Mater Res B Appl Biomater 106:1421-1430|
|Denry, Isabelle; Goudouri, Ourania-Menti; Harless, Jeffrey et al. (2018) Rapid vacuum sintering: A novel technique for fabricating fluorapatite ceramic scaffolds for bone tissue engineering. J Biomed Mater Res B Appl Biomater 106:291-299|
|Denry, Isabelle; Kuhn, Liisa T (2016) Design and characterization of calcium phosphate ceramic scaffolds for bone tissue engineering. Dent Mater 32:43-53|
|Denry, I; Kelly, J R (2014) Emerging ceramic-based materials for dentistry. J Dent Res 93:1235-42|
|Denry, Isabelle; Holloway, Julie A (2014) Low temperature sintering of fluorapatite glass-ceramics. Dent Mater 30:112-21|
|Denry, I; Holloway, J A; Gupta, P K (2012) Effect of crystallization heat treatment on the microstructure of niobium-doped fluorapatite glass-ceramics. J Biomed Mater Res B Appl Biomater 100:1198-205|
|Kushwaha, Meenakshi; Pan, Xueliang; Holloway, Julie A et al. (2012) Differentiation of human mesenchymal stem cells on niobium-doped fluorapatite glass-ceramics. Dent Mater 28:252-60|