Nanoscale Polymeric Templates for Orthopedic Tissue Engineering

用于骨科组织工程的纳米级聚合物模板

• 批准号: 7990844
• 负责人: Ketul Chandrakant Popat
• 金额: $ 14.88万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7990844
• 关键词: Accounting; Address; Alkaline Phosphatase; Aluminum Oxide; Architecture; Arthrodesis; Arthroplasty; Autologous Transplantation; Behavior; Biocompatible; Biodegradation; Biological; Biomimetics; Bone Marrow; Bone Regeneration; Bone Tissue; Bone Transplantation; Bone neoplasms; Cell Adhesion; Cells; Cicatrix; Cultured Cells; Defect; Deposition; Development; Encapsulated; Engineering; Environment; Excision; Exploratory/Developmental Grant; Extracellular Matrix Proteins; Fracture; Future; Goals; Gold; Growth; Healed; Hydroxyapatites; Implant; Infection; Inflammation; Investigation; Joints; Knee; Label; Measures; Mechanics; Membrane; Mesenchymal Stem Cells; Morbidity - disease rate; Morphology; Motivation; Nanotopography; Nanotubes; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Natural regeneration; Operative Surgical Procedures; Orthopedics; Osseointegration; Osteogenesis; Osteogenesis Imperfecta; Osteoporosis; Pain; Pathology; Phenotype; Physiological; Porosity; Process; Production; Proliferating; Property; Rehabilitation therapy; Research; Research Support; Risk; Role; Science; Signal Transduction; Site; Spinal; Stem cells; Structure-Activity Relationship; Surface; Techniques; Technology; Tissue Engineering; Tissues; Transplantation; Transplanted tissue; United States National Institutes of Health; Work; base; biomaterial compatibility; bone; cell motility; controlled release; conventional therapy; design; economic impact; healing; hip replacement arthroplasty; implantation; in vivo; innovation; innovative technologies; interest; migration; nano; nanoscale; nanostructured; nanowire; osteogenic; polycaprolactone; prevent; programs; public health relevance; response; sample fixation; scaffold; standard care; stem cell differentiation; tissue culture; tissue regeneration

DESCRIPTION (provided by applicant): Autogenous cancellous bone is currently the most widely used bone graft material. However, there are several problems associated with autogenous cancellous bone grafts such as additional scar tissue formation, donor site morbidity, pain, prolonged rehabilitation, increased risk of deep infection, inflammation and restricted availability. These problems have motivated the design of synthetic bone scaffolds as a replacement for autogenous cancellous bone grafts. Synthetic tissue engineering scaffolds provide a biomimetic construct, which employ natural biological cascades to promote healing, and native tissue integration and regeneration. As the role of cell signaling and subsequent functionality in tissue engineering becomes more clear, tissue engineers are developing multifunctional bioactive scaffolds designed to accelerate the natural healing process, which simultaneously prevent pathologies that may occur post-implantation. Ideal scaffolds are capable of presenting a physiochemical biomimetic environment while biodegrading as native tissue integrates and actively promotes or prevents desirable and undesirable physiological responses respectively. Thus, the hypotheses and specific aims of the proposed research program are: Specific Aim 1 Develop processes for optimal fabrication of highly uniform micro/nano-hierarchal scaffolds of controllable geometry and bioactivity from PCL for orthopedic tissue engineering applications Specific Aim 2 Determine the effect of nanostructured surface morphology (size of nanowires) on the behavior of MSCs (adhesion, viability, morphology, differentiation, phenotype) both short term (days) and long term (several weeks) Specific Aim 3 Determine in vivo biocompatibility and oseointegration properties of micro/nano- hierarchal scaffolds Considering the limitations of the current gold-standard treatment for critical sized defects, biodegradable synthetic bone scaffolds hold a lot of promise for future treatment regimes. Therefore, synthetic bone tissue engineered scaffolds have been aggressively pursued in the last two decades, and now have emerged as a promising alternative to conventional therapies for repairing bone defects. The fundamental concept behind tissue engineering is to utilize the body's natural biological response to tissue damage in conjunction with engineering principles. Successful synthetic bone scaffolds promotes progenitor cell migration on to the scaffold (osteoconduction), support or induce osteogenic differentiation (osteoinduction), and finally integrate with host tissue (osseointegration). Additional critical aspects of successful bone scaffolds include biocompatibility, temporary mechanical stability, biodegradability, porosity, and controlled release of bioactive molecules to accelerate healing and/or prevent undesired pathologies. This proposed project outlines the motivation and reasoning behind the development of the PCL nanowire surfaces. PUBLIC HEALTH RELEVANCE: Autogenous cancellous bone is currently the most widely used bone graft material. However, there are several problems associated with autogenous cancellous bone grafts such as additional scar tissue formation, donor site morbidity, pain, prolonged rehabilitation, increased risk of deep infection, inflammation and restricted availability. These problems have motivated the design of synthetic bone scaffolds as a replacement for autogenous cancellous bone grafts. This proposed project outlines the motivation and reasoning behind the development of the polymeric nanowire surfaces as a bone graft material.

描述（由申请人提供）：自动取消骨是当前使用最广泛的骨移植物材料。但是，有几个问题与自体取消骨移植物有关，例如额外的疤痕组织形成，供体部位发病，疼痛，长期康复，增加深层感染的风险，炎症和可用性受限。这些问题激发了合成骨支架的设计，以替代自源性骨移植。合成组织工程支架提供了一种仿生结构，它采用天然生物级联反应来促进愈合，以及天然组织的整合和再生。随着细胞信号传导和随后在组织工程中的功能的作用变得越来越清晰，组织工程师正在开发旨在加速自然愈合过程的多功能生物活性支架，这同时可以防止植入后可能发生的病理。理想的脚手架能够呈现生理化学仿生环境，同时生物降解作为天然组织会融合并积极促进或防止理想和不良的生理反应。因此，拟议的研究计划的假设和具体目标是：特定目标1开发过程，以最佳制造可控几何形状的高度均匀的微/纳米等级脚手架和PCL的生物活性，用于骨科组织工程的PCL和生物活性的特定目的。形态学，差异，表型）短期（天）和长期（几周）特定目的3确定微/纳米分层型的体内生物相容性和稳定性，考虑到当前金色标准尺寸缺陷的局限性的局限因此，在过去的二十年中，合成的骨组织工程脚手架已经积极追捕，现在已经成为用于修复骨缺损的常规疗法的有前途的替代方法。组织工程背后的基本概念是利用人体与工程原理结合组织对组织损伤的自然生物反应。成功的合成骨支架可促进祖细胞迁移到支架（骨降低），支撑或诱导成骨分化（骨诱导），并最终与宿主组织（Ossecletration）整合在一起。成功的骨支架的其他关键方面包括生物相容性，暂时的机械稳定性，生物降解性，孔隙率和受控生物活性分子的释放，以加速愈合和/或预防不希望的病理。该拟议项目概述了PCL纳米线表面发展背后的动机和推理。 公共卫生相关性：自体取消骨骼目前是使用最广泛的骨移植物材料。但是，有几个问题与自体取消骨移植物有关，例如额外的疤痕组织形成，供体部位发病，疼痛，长期康复，增加深层感染的风险，炎症和可用性受限。这些问题激发了合成骨支架的设计，以替代自源性骨移植。该提议的项目概述了聚合物纳米线表面作为骨移植物质的发展背后的动机和推理。