Micro- and nanofiber enabled biomimetic periosteum for bone repair and reconstruction

节段性骨缺损常因创伤、感染和肿瘤切除而发生。 骨科和颅面临床实习。骨移植已被用作主要的治疗方法。 重建大段骨缺损的治疗方案。每年有60多万例骨移植 手术在美国进行，全世界有超过220万例手术。当前 骨移植材料的选择包括自体骨移植、同种异体骨移植和合成材料。而自体移植物是 自体移植被认为是“黄金标准”，但由于供体部位的限制，自体移植的应用极为有限。 大段骨缺损的发病率和修复能力有限。同种异体移植仍然是修复的首选 需要立即支持的大型缺陷。然而，由于缺乏可行的血管生成和成骨细胞 同种异体骨移植的细胞、愈合和结合是极其缓慢和有限的。有限的骨形成， 同种异体结构移植物的再血管化和重塑特性直接与25%到35%相关 由于骨不连，植入后2年内的失败率和10年内60%的失败率， 灭活骨微裂纹的感染和扩展。要克服与以下各项相关的限制 结构性同种异体移植，我们提出了一种组织工程策略，通过创建功能性的 骨膜促进同种异体骨结合和改建。随着一种多功能的 电纺技术和一种新的近场静电打印(NFEP)方法，我们目前的建议 寻求将几个科学和技术进步结合到创造一种基于微/纳米纤维的， 多模块、无血运的骨组织移植，具有生长因子释放特性，模拟高度 有组织的、有功能的骨膜，用于重建大型骨缺损区。关键分子的掺入 同时促进成骨和血管生成的信号和相关的细胞来源将被解决。 该项目的完成可以1)建立一种新的方法来控制 成骨和血管生成/血管生成细胞形成多功能三维细胞结构；2)提供 关于工程血管网络与宿主循环的吻合和整合的机械信息； 3)为理解细胞-基质相互作用和工程应用提供了基础和手段 引导祖细胞分化以修复和重建骨缺损的微环境。这个 我们目前项目的成功还将为设计更复杂的血管奠定基础 层次化模式，可以实现对各种组织重建的广泛影响。在临床上， 该项目的成功可能进一步提供理论基础和战略，以有效地提供成骨和 用于增强颅面和长骨修复和重建的血管生成/血管生成细胞群 骨缺损症。

Segmental bone defects frequently occur as a result of trauma, infection and tumor resection in orthopaedic and craniofacial clinical practice. Bone graft transplantation has been used as the primary treatment regimen for reconstruction of large segmental bone defects. Each year over 600,000 bone grafting procedures are performed in the United States, and more than 2.2 million are performed worldwide. Current choices for bone grafting materials include autograft, allograft, and synthetic materials. While an autograft is considered as the “gold standard”, the use of autograft is extremely limited due to the associated donor site morbidity and the restricted availability for repair of large bone defects. Allograft remains a top choice for repair of large defects that require immediate support. However, due to the lack of viable angiogenic and osteogenic cells, healing and incorporation of bone allograft are extremely slow and limited. The limited bone forming, revascularizing and remodeling properties of structural allograft are directly associated with a 25% to 35% failure rate within 2 years and a 60% failure rate in 10 years after implantation as a result of non-union, infection and propagation of microcracks of the devitalized bone. To overcome the limitation associated with structural allograft, we proposed a tissue engineering strategy to revitalize allograft by creating a functional periosteum to enhance allograft incorporation and remodeling. With the development of a versatile electrospinning technique and a novel near-field electrostatic printing (NFEP) method, our current proposal seeks to combine several scientific and technical advances into the creation of a micro/nanofibers-based, multi-modular, prevascularized bone tissue graft, with growth factor releasing property, simulating the highly organized and functional periosteum for reconstruction of large bone defects. Incorporation of key molecular signals and relevant cellular sources that promote both osteogenesis and angiogenesis will be addressed. The completion of the project could 1) establish a novel methodology to control the spatiotemporal assembly of osteogenic and angiogenic/vasculogenic cells into a multi-functional 3-dimensional cellular construct; 2) offer mechanistic information on anastomosis and integration of engineered vascular networks with host circulation; and 3) provide the basis and means for understanding of cell-matrix interactions and for engineering of microenvironments to direct progenitor cell differentiation for bone defect repair and reconstruction. The success of our current project will also lay foundation for engineering of more sophisticated blood vessels with hierarchical patterns, which could achieve a wide impact on various tissue reconstructions. Clinically, the success of the project could further offer rationales and strategies to effectively deliver osteogenic and angiogenic/vasculogenic cell populations for enhanced repair and reconstruction of both craniofacial and long bone defects.