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

微米和纳米纤维仿生骨膜用于骨修复和重建

• 批准号: 9755362
• 负责人: Hongjun Wang
• 金额: $ 56.39万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9755362
• 关键词: 3-Dimensional; Address; Adipose tissue; Allografting; Anastomosis - action; Autologous Transplantation; Biological Assay; Biomechanics; Biomimetics; Blood Circulation; Blood Vessels; Bone Marrow; Bone Regeneration; Bone Surface; Bone Tissue; Bone Transplantation; Bone remodeling; Bone structure; Caliber; Cell Differentiation process; Cell Survival; Cells; Cephalic; Clinical; Collagen; Defect; Development; Electrospinning; Electrostatics; Engineering; Erinaceidae; Excision; Failure; Fiber; Foundations; Genes; Gold; Growth Factor; Histologic; Histology; Hydroxyapatites; Implant; In Vitro; Infection; Interdisciplinary Study; Laboratories; Laser Scanning Microscopy; Legal patent; Maintenance; Mediating; Mesenchymal Stem Cells; Methodology; Methods; Modeling; Molecular; Morbidity - disease rate; Mus; N-terminal; Organ Transplantation; Orthopedics; Osseointegration; Osteogenesis; Pathway interactions; Pattern; Peptides; Perfusion; Pericytes; Periosteum; Permeability; Population; Printing; Property; Regulation; Resolution; Role; SHH gene; Signal Transduction; Site; Source; Stem cells; Structure; System; Techniques; Technology; Testing; Therapeutic; Time; Tissue Engineering; Tissue Grafts; Translations; Transplantation; Transplanted tissue; Trauma; Treatment Protocols; United States; Vascularization; Work; X-Ray Computed Tomography; allogenic bone transplantation; angiogenesis; base; bone; bone engineering; clinical practice; clinical translation; craniofacial; craniofacial bone; healing; implantation; improved; in vivo; long bone; microCT; mouse model; nano; nanofiber; neovascularization; novel; novel strategies; off-patent; osteogenic; overexpression; polycaprolactone; progenitor; reconstruction; recruit; release factor; repaired; scaffold; spatiotemporal; stem cell differentiation; success; three dimensional cell culture; tissue reconstruction; transplant model; tumor; vascular tissue engineering; vasculogenesis

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.

节段性骨缺损常因创伤、感染和肿瘤切除而发生， 整形外科和颅面临床实践。骨移植已被用作主要的 大段骨缺损重建的治疗方案。每年有超过60万例骨移植手术 手术在美国进行，在全世界进行了220多万次。电流 骨移植材料的选择包括自体移植物、同种异体移植物和合成材料。而自体移植 作为“金标准”，由于相关的供体部位， 发病率和修复大骨缺损的可用性有限。同种异体移植仍然是修复的首选 需要立即支持的重大缺陷。然而，由于缺乏可行的血管生成和成骨 细胞，愈合和骨同种异体移植物的结合是非常缓慢和有限的。有限的骨形成， 结构性同种异体移植物的血管重建和重塑特性与25%至35%的 由于骨不连，植入后2年内的失败率和10年内的失败率为60%， 感染和失活骨微裂纹的扩展。为了克服与 结构性同种异体移植物，我们提出了一种组织工程策略，通过创建功能性 骨膜以增强同种异体移植物结合和重塑。随着多功能 静电纺丝技术和一种新的近场静电印刷（NFEP）方法，我们目前的建议 试图将联合收割机几种科学和技术进步结合起来， 多模块化预血管化骨组织移植物，具有生长因子释放特性， 组织化和功能性骨膜用于重建大面积骨缺损。关键分子掺入 促进骨生成和血管生成的信号和相关细胞来源将被解决。 该项目的完成可以1）建立一种新的方法来控制时空组装， 成骨和血管生成/血管生成细胞形成多功能三维细胞构建体; 2）提供 关于工程血管网络与宿主循环的吻合和整合的机制信息; 和3）为理解细胞-基质相互作用和工程化提供基础和手段， 微环境来指导祖细胞分化用于骨缺损修复和重建。的 我们目前项目的成功也将为更复杂的血管工程奠定基础， 分层模式，这可以实现对各种组织重建的广泛影响。临床上 该项目的成功可以进一步提供有效地提供成骨和 血管生成/血管生成细胞群用于增强颅面和长 骨缺损