Dadsetan Mahrokh, Guda Teja, Runge M Brett, Mijares Dindo, LeGeros Racquel Z, LeGeros John P, Silliman David T, Lu Lichun, Wenke Joseph C, Brown Baer Pamela R, Yaszemski Michael J
Biomaterials and Tissue Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, TX, USA.
Acta Biomater. 2015 May;18:9-20. doi: 10.1016/j.actbio.2014.12.024. Epub 2015 Jan 7.
Various calcium phosphate based coatings have been evaluated for better bony integration of metallic implants and are currently being investigated to improve the surface bioactivity of polymeric scaffolds. The aim of this study was to evaluate the role of calcium phosphate coating and simultaneous delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the in vivo bone regeneration capacity of biodegradable, porous poly(propylene fumarate) (PPF) scaffolds. PPF scaffolds were coated with three different calcium phosphate formulations: magnesium-substituted β-tricalcium phosphate (β-TCMP), carbonated hydroxyapatite (synthetic bone mineral, SBM) and biphasic calcium phosphate (BCP). In vivo bone regeneration was evaluated by implantation of scaffolds in a critical-sized rabbit calvarial defect loaded with different doses of rhBMP-2. Our data demonstrated that scaffolds with each of the calcium phosphate coatings were capable of sustaining rhBMP-2 release and retained an open porous structure. After 6weeks of implantation, micro-computed tomography revealed that the rhBMP-2 dose had a significant effect on bone formation within the scaffolds and that the SBM-coated scaffolds regenerated significantly greater bone than BCP-coated scaffolds. Mechanical testing of the defects also indicated restoration of strength in the SBM and β-TCMP with rhBMP-2 delivery. Histology results demonstrated bone growth immediately adjacent to the scaffold surface, indicating good osteointegration and osteoconductivity for coated scaffolds. The results obtained in this study suggest that the coated scaffold platform demonstrated a synergistic effect between calcium phosphate coatings and rhBMP-2 delivery and may provide a promising platform for the functional restoration of large bone defects.
为了使金属植入物更好地与骨结合,人们对各种磷酸钙基涂层进行了评估,目前正在研究这些涂层以提高聚合物支架的表面生物活性。本研究的目的是评估磷酸钙涂层和重组人骨形态发生蛋白-2(rhBMP-2)的同步递送对可生物降解的多孔聚富马酸丙二醇酯(PPF)支架体内骨再生能力的作用。PPF支架用三种不同的磷酸钙制剂进行了涂层处理:镁取代的β-磷酸三钙(β-TCMP)、碳酸羟基磷灰石(合成骨矿物质,SBM)和双相磷酸钙(BCP)。通过将支架植入载有不同剂量rhBMP-2的临界大小兔颅骨缺损中来评估体内骨再生情况。我们的数据表明,每种磷酸钙涂层的支架都能够维持rhBMP-2的释放并保留开放的多孔结构。植入6周后,微型计算机断层扫描显示,rhBMP-2剂量对支架内的骨形成有显著影响,并且SBM涂层的支架比BCP涂层的支架再生的骨明显更多。对缺损部位的力学测试还表明,在递送rhBMP-2的情况下,SBM和β-TCMP部位的强度得到了恢复。组织学结果显示,骨在紧邻支架表面处生长,表明涂层支架具有良好的骨整合性和骨传导性。本研究获得的结果表明,涂层支架平台在磷酸钙涂层和rhBMP-2递送之间表现出协同效应,可能为大骨缺损的功能修复提供一个有前景的平台。