Polysaccharide putty formulations for tissue regeneration
用于组织再生的多糖腻子配方
基本信息
- 批准号:10627055
- 负责人:
- 金额:$ 37.35万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAcetatesAddressBiocompatible MaterialsBiological AssayBone DensityBone MatrixBone RegenerationBone TissueBone TransplantationCalvariaCell Culture TechniquesCelluloseCephalicCeramicsClinicalComplementComplexCoupledDefectDevelopmentDiffusionDrug or chemical Tissue DistributionEconomic BurdenEnabling FactorsEnsureEquilibriumExcipientsExtracellular MatrixFDA approvedFormulationFractureFutureGenerationsGrowthGrowth FactorHydrogelsImpaired healingIn VitroKnowledgeMechanicsMesenchymal Stem CellsModelingMoldsNanotubesNatural regenerationOryctolagus cuniculusOsteoblastsOsteoclastsOsteogenesisPharmaceutical PreparationsPhysiologic pulsePhysiologicalPlantsPolymersPolymethyl MethacrylatePolysaccharidesPorosityPropertyProteinsResearchShapesSiteSolubilitySterilizationSystemTechnologyTemperatureTestingTimeTime FactorsTissuesVariantVascularizationVertebral columnWeight-Bearing stateWorkbiomaterial compatibilitybonebone engineeringbone healingbone repairbone strengthcalcium phosphatecell behaviorclaycomparison controlcortical bonecraniofacialdemineralizationdesigndynamic systemefficacy testingflat boneflexibilityhalloysiteimplantable deviceimplantationin vivoinnovationlong bonemouse modelnanonovelphthalatesrelease factorrepairedscaffoldstem cell deliverysubcutaneousthree dimensional structuretissue regenerationtissue repairulna
项目摘要
Project Summary/Abstract
The broad, long-term objectives of this proposal are to enhance the utility of cellulose-based biomaterials for
tissue repair by developing and evaluating a new and innovative composite that address current limitations.
Bacterial cellulose hydrogels and extracellular matrices have shown excellent regeneration capabilities in
multiple tissue types. However, these materials lack mechanical strength and degradation features needed for
specific applications such as bone repair, and have limited options for storage, handling, and sterilization. Plant-
derived cellulose in its derivative cellulose acetate (CA) form is capable of creating mechanically competent
porous scaffolds that are effective in bone regeneration. However, premade CA scaffolds with defined sizes,
shapes, and pore properties present challenges in adapting to complex bone defects. Additionally, the relatively
slow degradation rate of cellulose/CA can limit its ability to control factor release and heal bone. Combining CA
with CA phthalate (CAP) and nanoclay (NC) has the potential to address some of these weaknesses. This
cellulose-based composite forms a putty that can be molded into complex shapes and becomes strong as it
hardens, making it adaptable to diverse bone defects. Under physiologic conditions, CAP erodes before the
slower-degrading CA matrix, enabling a dynamic system that generates interconnected pores and tunable
growth factor release profiles and degradation. A CA/CAP/NC composite allows flexible incorporation of multiple
bioactive factors for varied effects: within CA for early, sustained release; within CAP for pulsed release; and/or
into NC embedded within the CA/CAP for delayed, sustained release. This also allows factors to be released in
parallel and/or sequentially. Detailed, long-term in vitro and in vivo characterizations of this cellulose biomaterial,
including its ability to balance strength and porosity and the effects of osteoclasts on its degradation, remain
knowledge gaps for advancing this transformative and natural biomaterial platform. Based on current knowledge,
it is hypothesized that this dynamic cellulose-based putty will impart composition-dependent changes of strength
and erosion in 3D microenvironments leading to varied bioactive factor release rates, vasculature development,
and tissue ingrowth during bone repair. This will be tested in four Specific Aims: Aim 1: Characterize
physicochemical and release properties of novel cellulose derivatives and compositions in vitro. Aim 2: Evaluate
biocompatibility and bioactivity of released molecules in an in vivo subcutaneous implantation model. Aim 3:
Evaluate cellular effects of putty formulations with early to long-term release profiles on a cranial flat-bone healing
defect. Aim 4: Assess putty formulations with early to long-term release profiles on bone healing at a load-
bearing site in a critical-sized long-bone defect in rabbit ulna. These studies will address several knowledge gaps
for using cellulose biomaterials in bone healing. If this enabling putty technology is successful, it may be
transformative to the field and adapted for other repair challenges in bone as well as a coating for biomedical
implants.
项目摘要/摘要
这项提议的广泛和长期目标是提高基于纤维素的生物材料在
通过开发和评估一种新的、创新的复合材料来解决目前的局限性,从而修复组织。
细菌纤维素水凝胶和细胞外基质在
多种组织类型。然而,这些材料缺乏所需的机械强度和降解特性
可用于骨修复等特定应用,并且储存、处理和杀菌的选择有限。植物-
衍生的纤维素以其衍生的纤维素醋酸酯(CA)的形式能够产生具有机械性能的
在骨再生方面有效的多孔支架。然而,预制的CA支架具有定义的尺寸,
在适应复杂的骨缺损方面,形状和毛孔特性提出了挑战。另外,相对的
纤维素/CA的缓慢降解速度限制了其控制因子释放和修复骨的能力。组合CA
使用CA邻苯二甲酸盐(CAP)和纳米粘土(NC)有可能解决其中一些弱点。这
纤维素基复合材料形成一种油灰,这种油灰可以模制成复杂的形状,并随着
硬化,使其适应不同的骨缺陷。在生理条件下,CAP在
降解较慢的CA矩阵,支持生成相互连接的毛孔和可调的动态系统
生长因子释放谱和降解。CA/CAP/NC组合允许灵活地合并多个
不同作用的生物活性因子:在CA内用于早期、持续释放;在CAP内用于脉冲释放;和/或
植入CA/CAP内的NC中,用于延迟、持续释放。这也允许因子在
并行和/或顺序地。这种纤维素生物材料的详细、长期的体外和体内表征,
包括其平衡强度和孔隙度的能力以及破骨细胞对其降解的影响
推动这一变革性的自然生物材料平台的知识差距。根据目前的知识,
据推测,这种动态的纤维素基油灰将产生与组成有关的强度变化
以及3D微环境中的侵蚀导致不同的生物活性因子释放率、血管发育、
在骨修复过程中组织向内生长。这将在四个具体目标中进行测试:目标1:确定特征
新型纤维素衍生物和组合物的物理化学和体外释放特性。目标2:评估
体内皮下植入模型中释放分子的生物相容性和生物活性。目标3:
评价早期和长期释放曲线的油灰制剂对颅骨扁平骨愈合的细胞效应
叛逃。目标4:评估具有早期和长期释放曲线的油灰配方在负荷下对骨愈合的影响
在兔尺骨一个临界大小的长骨缺损处的承载部位。这些研究将解决几个知识差距
在骨愈合中使用纤维素生物材料。如果这种启用PuTTY的技术成功,它可能是
适用于骨领域的其他修复挑战以及用于生物医学的涂层
植入物。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Sangamesh Gurappa Kumbar其他文献
Sangamesh Gurappa Kumbar的其他文献
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{{ truncateString('Sangamesh Gurappa Kumbar', 18)}}的其他基金
Engineered Matrices with Electrical and Chemical Stimulation for Peripheral Nerve Repair
用于周围神经修复的具有电和化学刺激的工程基质
- 批准号:
10592729 - 财政年份:2022
- 资助金额:
$ 37.35万 - 项目类别:
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