Shape Memory Polymer Scaffolds to Treat Bone Defects in Patients with Alzheimer's Disease

形状记忆聚合物支架治疗阿尔茨海默病患者的骨缺损

• 批准号: 10442203
• 负责人: Melissa Grunlan
• 金额: $ 7.01万
• 依托单位: RENSSELAER POLYTECHNIC INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10442203
• 关键词: Adhesions; Alzheimer' s Disease; Alzheimer' s disease patient; Autologous; Biocompatible Materials; Bone Density; Bone Diseases; Bone Transplantation; Cells; Complication; Defect; Disease; Environment; Exogenous Factors; Fibronectins; Fracture; Fracture Healing; General Population; Homeostasis; Hydroxyapatites; Impaired healing; Integrins; Laminin; Ligands; Memory; Mesenchymal Stem Cells; Nerve; Neurodegenerative Disorders; Neurons; Osteogenesis; Osteoporotic; Patients; Peripheral; Phenotype; Polymers; Shapes; TNF gene; Vascularization; base; bone; bone healing; design; healing; improved; mimetics; nanoscale; novel; patient population; repaired; scaffold

ABSTRACT Alzheimer’s disease (AD) is a devastating neurodegenerative disorder which has systemic effects. For instance, AD patients generally suffer from low bone mineral density even in early stages of the disease, and as such are more prone to bone fractures relative to the general population. Due to the loss in bone density, autologous bone grafts are generally not an option in fracture repair for the AD patient population. Furthermore, healing of fractures in AD is usually slow and often results in delayed or incomplete healing. This delayed healing is on top of the already high complication rates often associated with defect repair. The loss in bone mineral density in AD appears to be due in part to the abnormal peripheral sympathetic nerve (SN) activation often associated with the disease. Particularly, elevated levels of TNFα in the osteoporotic AD bone are correlated with abnormally active SNs, which are known to critically influence bone healing, resorption, vascularization, and homeostasis. Thus, a biomaterial scaffold which stimulates a more normal phenotype in growing SNs may enhance osteogenesis and bone healing in AD fracture repair. Recently, we proposed a new scaffold design based on a novel class of shape memory polymers (SMPs). Avoiding the use of exogenous factors – which can cause undesired off-target effects - these scaffolds provide intrinsic osteoinductivity through the incorporated adhesion ligand(s) and a nanoscale polydopamine coating known to support osteogenesis as well as the formation of hydroxyapatite. Interestingly, polydopamine coatings have also recently been demonstrated to stimulate extension and phenotypic maturation in SN-like cells, as have fibronectin- and laminin-derived integrin adhesion ligands. This R03 proposal focuses on tailoring the integrin adhesion-based landscape of SMP scaffolds to promote desired SN cell and MSC phenotypes within the context of an osteo- and neuro-inductive polydopamine base. This proposal is unique in its focus on tailoring the phenotype of ingrowing SN cells toward improving MSC osteogenesis and doing so within a disease- mimetic “inflamed” environment.

摘要

项目成果

The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease.

• DOI: 10.3389/fnagi.2020.583884
• 发表时间: 2020
• 期刊: Frontiers in aging neuroscience
• 影响因子: 4.8
• 作者: Culibrk RA;Hahn MS
• 通讯作者: Hahn MS