Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Department of Orthopedic Surgery and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Adv Healthc Mater. 2018 May;7(10):e1701415. doi: 10.1002/adhm.201701415. Epub 2018 Mar 2.
An ideal synthetic bone graft is a combination of the porous and nanofibrous structure presented by natural bone tissue as well as osteoinductive biochemical factors such as bone morphogenetic protein 2 (BMP-2). In this work, ultralight 3D hybrid nanofiber aerogels composed of electrospun PLGA-collagen-gelatin and Sr-Cu codoped bioactive glass fibers with incorporation of heptaglutamate E7 domain specific BMP-2 peptides have been developed and evaluated for their potential in cranial bone defect healing. The nanofiber aerogels are surgically implanted into 8 mm × 1 mm (diameter × thickness) critical-sized defects created in rat calvariae. A sustained release of E7-BMP-2 peptide from the degradable hybrid aerogels significantly enhances bone healing and defect closure over 8 weeks in comparison to unfilled defects. Histomorphometry and X-ray microcomputed tomography (µ-CT) analysis reveal greater bone volume and bone formation area in case of the E7-BMP-2 peptide loaded hybrid nanofiber aerogels. Further, histopathology data divulged a near complete nanofiber aerogel degradation along with enhanced vascularization of the regenerated tissue. Together, this study for the first time demonstrates the fabrication of 3D hybrid nanofiber aerogels from 2D electrospun fibers and their loading with therapeutic osteoinductive BMP-2 mimicking peptide for cranial bone tissue regeneration.
理想的合成骨移植物是天然骨组织的多孔和纳米纤维结构与骨形态发生蛋白 2(BMP-2)等成骨诱导生化因子的结合。在这项工作中,开发了由静电纺丝 PLGA-胶原蛋白-明胶和 Sr-Cu 共掺杂生物活性玻璃纤维组成的超轻 3D 混合纳米纤维气凝胶,并掺入了七肽 E7 结构域特异性 BMP-2 肽,用于评估其在颅骨缺损愈合中的潜力。将纳米纤维气凝胶通过手术植入大鼠颅骨中创建的 8mm×1mm(直径×厚度)临界尺寸的缺损中。与未填充的缺损相比,可降解混合气凝胶中 E7-BMP-2 肽的持续释放可显著增强 8 周内的骨愈合和缺损闭合。组织形态计量学和 X 射线微计算机断层扫描(µ-CT)分析表明,负载 E7-BMP-2 肽的混合纳米纤维气凝胶的骨体积和骨形成面积更大。此外,组织病理学数据显示,纳米纤维气凝胶几乎完全降解,同时再生组织的血管化增强。总之,这项研究首次证明了 3D 混合纳米纤维气凝胶可以从 2D 静电纺丝纤维制备,并可以负载治疗性成骨诱导的 BMP-2 模拟肽来再生颅骨组织。