权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的阿尔茨海默病（AD）是一种破坏性的神经退行性疾病，具有全身性影响。为了例如，即使在疾病的早期阶段，AD 患者通常也患有低骨矿物质密度，并且因此，相对于一般人群，他们更容易发生骨折。由于骨密度下降，自体骨移植通常不是 AD 患者骨折修复的选择。此外，AD 骨折的愈合通常很慢，并且常常导致愈合延迟或不完全。这除了通常与缺损修复相关的本来就很高的并发症发生率之外，还存在延迟愈合。损失在 AD 中的骨矿物质密度似乎部分归因于周围交感神经 (SN) 异常激活通常与疾病有关。特别是，骨质疏松性 AD 骨中 TNFα 水平升高与异常活跃的 SN 相关，已知这些 SN 会严重影响骨愈合、吸收、血管化和体内平衡。因此，刺激更正常表型的生物材料支架生长的 SN 可能会增强 AD 骨折修复中的成骨和骨愈合。最近，我们提出了一个新的基于新型形状记忆聚合物（SMP）的支架设计。避免使用外源性药物因素 - 可能导致不良的脱靶效应 - 这些支架提供内在的骨诱导性通过结合的粘附配体和已知支持的纳米级聚多巴胺涂层成骨以及羟基磷灰石的形成。有趣的是，聚多巴胺涂层还具有最近被证明可以刺激 SN 样细胞的延伸和表型成熟，纤连蛋白和层粘连蛋白衍生的整合素粘附配体。这个 R03 提案的重点是定制整合素基于粘附的 SMP 支架景观，以促进所需的 SN 细胞和 MSC 表型骨和神经诱导性聚多巴胺碱的背景。该提案的独特之处在于它注重剪裁向内生长的 SN 细胞的表型可改善 MSC 成骨作用，并在疾病中实现这一目标- 模仿“发炎”的环境。