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.

节段性骨缺损常因外伤、感染、肿瘤切除等原因而发生。 骨科和颅面骨移植已作为主要临床实践。 大节段骨缺损重建治疗方案每年超过60万例植骨。 手术在美国进行，目前全球已实施超过 220 万例。 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。 自体移植被认为是“黄金标准”，但由于相关的供体部位，其使用极为有限 较大骨缺损的发病率和修复可用性有限仍然是修复的首选。 然而，由于缺乏可行的血管生成和成骨，需要立即支持的大缺陷。 细胞、同种异体骨的愈合和融合极其缓慢且有限的骨形成， 结构同种异体移植物的血运重建和重塑特性与 25% 至 35% 直接相关 由于不愈合，植入后 2 年内失败率和 10 年内失败率达 60%， 感染和失活骨微裂纹的传播克服与相关的限制。 结构同种异体移植物，我们提出了一种组织工程策略，通过创建功能性同种异体移植物来振兴同种异体移植物 骨膜增强同种异体移植物的融合和重塑。 静电纺丝技术和新型近场静电印刷（NFEP）方法，我们目前的建议 寻求将多项科学和技术进步结合起来，创造出一种基于微/纳米纤维的、 多模块、预血管化骨组织移植物，具有生长因子释放特性，模拟高度 用于重建大骨缺损的组织化和功能性骨膜。 将讨论促进骨生成和血管生成的信号和相关细胞来源。 该项目的完成可以1）建立一种新的方法来控制时空组装 成骨细胞和血管生成细胞形成多功能 3 维细胞结构 2) 提供； 关于工程化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设计提供基础和手段 微环境指导祖细胞分化以进行骨缺损修复和重建。 我们当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，可以对临床上的各种组织重建产生广泛的影响。 该项目的成功可以进一步提供有效提供成骨和治疗的基本原理和策略。 血管生成/血管生成细胞群，用于增强颅面和长颅骨的修复和重建 骨缺损。