Biomimetic Scaffold Delivering Osteogenic Molecules for Alveolar Bone Engineering
为牙槽骨工程输送成骨分子的仿生支架
基本信息
- 批准号:8434110
- 负责人:
- 金额:$ 18.48万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-04-01 至 2015-03-31
- 项目状态:已结题
- 来源:
- 关键词:3D PrintAdverse effectsAlginatesAlveolarAlveolar Ridge AugmentationAlveolar ridgeApatitesArchitectureBiomimeticsBody FluidsBone Morphogenetic ProteinsBone RegenerationCalvariaCellsChitosanClinicalCommitComplexComputer AssistedCraniosynostosisCustomCystDataDefectDental ImplantsDoseElementsEnvironmentExcisionExhibitsGrowth FactorHumanImageImmersion Investigative TechniqueImplantation procedureIn VitroKineticsLaboratoriesMalignant NeoplasmsMandibleMarrowMaxillary SinusMechanicsMediatingMethodsMineralsModelingNatural regenerationNutritional RequirementsOsteogenesisPatientsPeriodontal DiseasesPhysiologicalPlatelet-Derived Growth FactorPolymersProcessPropertyProteinsProtocols documentationRattusReconstructive Surgical ProceduresResearchShapesSignaling MoleculeSimulateSiteSourceSpinalSpinal FusionStem cellsSystemTechniquesTestingTherapeuticTibial FracturesTissue EngineeringTooth LossTooth structureTranslationsTraumaX-Ray Computed Tomographyalveolar bonebasebonebone engineeringbone healingcomputer designin vivomeetingsnovelosteogenicosteogenic proteinosteoinductive factorplatelet-derived growth factor BBrepairedscaffold
项目摘要
DESCRIPTION (provided by applicant): Periodontal disease and malignant neoplasms are devastating complications often leading to the resection of large segments of the mandible. Various osteoinductive growth factor-based therapies have been developed in an attempt to find an effective and safer method of bone regeneration. In particular, bone morphogenetic proteins (BMPs) are currently approved for spinal fusion, tibial fracture repair, and alveolar ridge or maxillary sinus augmentation. However, BMPs are highly pleiotropic molecules and their supra-physiological high dose requirement leads to adverse side effects such as cyst formation, and inefficient bone formation. Thus, there is a need to develop alternative growth factor therapeutic strategies using osteoinductive factors with more specific osteogenic effects. Nell-1 (Nel-like protein-1) is a novel osteogenic protein originally identified in active bone forming sites of human craniosynostosis patients, and is believed to specifically target cells committed to the osteogenic lineage. To provide effective and safer bone regeneration for the repair of large, complex and structural defects, we propose a novel computer-designed, biomimetic scaffolding system for controlled local delivery of Nell-1. This system will consist of three-dimensional (3D) chitosan/alginate (Chi/Al) scaffolds with well-defined geometries on the macro- and micro-scales created from an indirect 3D printing technique in conjunction with biomimetic processing strategy to confer bone mineral-mimicking apatite microenvironment and osteogenic signaling molecules (Nell-1). To maximize bone regeneration, Nell-1 will be employed also in combination with platelet-derived growth factor-BB (PDGF-BB) in clinical use for the treatment of periodontal osseous defects. The specific hypothesis of this proposal is that controlled delivery of Nell-1+PDGF from computer-designed biomimetic scaffolds can enhance repair of alveolar bone defects. To investigate this hypothesis, we propose the following aims: 1) To develop biomimetic apatite-coated Chi/Al scaffolds with controlled architectures and delivery of osteogenic molecules (Nell-1+PDGF-BB); 2) To enhance alveolar bone regeneration by biomimetic scaffolds delivering Nell-1+PDGF-BB. Chi/Al scaffold architectures that facilitate mass transport and vessel ingrowth will be created from an indirect 3D printing technique. In this construct, we will create a biomimetic apatite coating and determine if apatite layer can increase Nell-1 and PDGF delivery efficiency. The bone formation efficacy of Nell-1 from the fabricated biomimetic scaffolds will be evaluated in a larger mandibular segmental defect model. In addition, we will also incorporate PDGF into the scaffolds and assess the effects of combined Nell-1+ PDGF on bone regeneration to maximize bone formation. The results from this proposal will be critical towards clinical translation of Nell-1 mediated therapeutics to augment alveolar bone regeneration while minimizing potential adverse effects of current osteoinductive therapeutics.
描述(申请人提供):牙周病和恶性肿瘤是毁灭性的并发症,往往导致切除下颌骨的大节段。各种基于骨诱导生长因子的治疗方法已经被开发出来,试图找到一种有效和更安全的骨再生方法。特别是,骨形态发生蛋白(BMPs)目前被批准用于脊柱融合、胫骨骨折修复、牙槽嵴或上颌窦增强。然而,bmp是高度多效性的分子,其超生理的高剂量要求导致不良副作用,如囊肿形成和骨形成效率低下。因此,有必要开发替代生长因子治疗策略,使用具有更特异性成骨作用的骨诱导因子。Nell-1 (nell -like protein-1)是一种新的成骨蛋白,最初在人类颅缝闭合患者的活性骨形成部位被发现,并且被认为是特异性靶向致力于成骨谱系的细胞。为了提供有效和更安全的骨再生修复大,复杂和结构缺陷,我们提出了一种新的计算机设计的仿生支架系统,用于控制局部递送Nell-1。该系统将由三维(3D)壳聚糖/海藻酸盐(Chi/Al)支架组成,在宏观和微观尺度上具有明确的几何形状,该支架由间接3D打印技术与仿生处理策略相结合创建,以赋予骨矿物模拟磷灰石微环境和成骨信号分子(Nell-1)。为了最大限度地实现骨再生,Nell-1还将与血小板衍生生长因子- bb (PDGF-BB)联合应用于临床治疗牙周骨缺损。本提议的具体假设是,计算机设计的仿生支架中有控制地递送Nell-1+PDGF可以增强牙槽骨缺损的修复。为了验证这一假设,我们提出了以下目标:1)开发具有结构可控和成骨分子(Nell-1+PDGF-BB)递送的仿生磷灰石包覆Chi/Al支架;2)通过植入Nell-1+PDGF-BB的仿生支架促进牙槽骨再生。Chi/Al支架结构将通过间接3D打印技术创建,以促进质量运输和容器的生长。在这个结构中,我们将创建一个仿生磷灰石涂层,并确定磷灰石层是否可以提高Nell-1和PDGF的传递效率。我们将在更大的下颌骨缺损模型中评估制备的仿生支架的成骨效果。此外,我们还将在支架中加入PDGF,并评估Nell-1+ PDGF联合使用对骨再生的影响,以最大限度地促进骨形成。这一建议的结果将对Nell-1介导的治疗方法的临床翻译至关重要,以增强牙槽骨再生,同时最大限度地减少当前骨诱导治疗的潜在不良影响。
项目成果
期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Design and Characterization of a Therapeutic Non-phospholipid Liposomal Nanocarrier with Osteoinductive Characteristics To Promote Bone Formation.
具有骨诱导特性的治疗性非磷脂脂质体纳米载体的设计和表征,可促进骨骼形成。
- DOI:10.1021/acsnano.7b02702
- 发表时间:2017-08-22
- 期刊:
- 影响因子:17.1
- 作者:Cui ZK;Kim S;Baljon JJ;Doroudgar M;Lafleur M;Wu BM;Aghaloo T;Lee M
- 通讯作者:Lee M
Enhanced osteogenesis of adipose derived stem cells with Noggin suppression and delivery of BMP-2.
- DOI:10.1371/journal.pone.0072474
- 发表时间:2013
- 期刊:
- 影响因子:3.7
- 作者:Fan J;Park H;Tan S;Lee M
- 通讯作者:Lee M
Glutamine-chitosan modified calcium phosphate nanoparticles for efficient siRNA delivery and osteogenic differentiation.
- DOI:10.1039/c5tb00843c
- 发表时间:2015-08-21
- 期刊:
- 影响因子:0
- 作者:Choi B;Cui ZK;Kim S;Fan J;Wu BM;Lee M
- 通讯作者:Lee M
Design of hydrogels to stabilize and enhance bone morphogenetic protein activity by heparin mimetics.
- DOI:10.1016/j.actbio.2018.03.034
- 发表时间:2018-05
- 期刊:
- 影响因子:9.7
- 作者:Kim S;Cui ZK;Kim PJ;Jung LY;Lee M
- 通讯作者:Lee M
Photocrosslinkable chitosan hydrogels functionalized with the RGD peptide and phosphoserine to enhance osteogenesis.
- DOI:10.1039/c6tb01154c
- 发表时间:2016-08-21
- 期刊:
- 影响因子:0
- 作者:Kim S;Cui ZK;Fan J;Fartash A;Aghaloo TL;Lee M
- 通讯作者:Lee M
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Min Lee其他文献
Min Lee的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Min Lee', 18)}}的其他基金
Hydrogel delivery of DBM and exosome mimetics for bone repair
水凝胶递送 DBM 和外泌体模拟物用于骨修复
- 批准号:
10412361 - 财政年份:2022
- 资助金额:
$ 18.48万 - 项目类别:
Hydrogel delivery of DBM and exosome mimetics for bone repair
水凝胶递送 DBM 和外泌体模拟物用于骨修复
- 批准号:
10681345 - 财政年份:2022
- 资助金额:
$ 18.48万 - 项目类别:
Tribbles homolog 3 and BMP-2 induced bone formation
Tribbles 同源物 3 和 BMP-2 诱导骨形成
- 批准号:
10397112 - 财政年份:2018
- 资助金额:
$ 18.48万 - 项目类别:
Tribbles homolog 3 and BMP-2 induced bone formation
Tribbles 同源物 3 和 BMP-2 诱导骨形成
- 批准号:
10165689 - 财政年份:2018
- 资助金额:
$ 18.48万 - 项目类别:
Biomimetic Scaffold Delivering Osteogenic Molecules for Alveolar Bone Engineering
为牙槽骨工程输送成骨分子的仿生支架
- 批准号:
8302181 - 财政年份:2012
- 资助金额:
$ 18.48万 - 项目类别:
Combined Effect of Noggin Suppression and Nell-1 on Bone Regeneration
Noggin 抑制和 Nell-1 对骨再生的联合作用
- 批准号:
8691729 - 财政年份:2011
- 资助金额:
$ 18.48万 - 项目类别:
Combined Effect of Noggin Suppression and Nell-1 on Bone Regeneration
Noggin 抑制和 Nell-1 对骨再生的联合作用
- 批准号:
8306999 - 财政年份:2011
- 资助金额:
$ 18.48万 - 项目类别:
Combined Effect of Noggin Suppression and Nell-1 on Bone Regeneration
Noggin 抑制和 Nell-1 对骨再生的联合作用
- 批准号:
8184767 - 财政年份:2011
- 资助金额:
$ 18.48万 - 项目类别:
Combined Effect of Noggin Suppression and Nell-1 on Bone Regeneration
Noggin 抑制和 Nell-1 对骨再生的联合作用
- 批准号:
8501385 - 财政年份:2011
- 资助金额:
$ 18.48万 - 项目类别:
相似海外基金
Unraveling Adverse Effects of Checkpoint Inhibitors Using iPSC-derived Cardiac Organoids
使用 iPSC 衍生的心脏类器官揭示检查点抑制剂的副作用
- 批准号:
10591918 - 财政年份:2023
- 资助金额:
$ 18.48万 - 项目类别:
Optimization of mRNA-LNP vaccine for attenuating adverse effects and analysis of mechanism behind adverse effects
mRNA-LNP疫苗减轻不良反应的优化及不良反应机制分析
- 批准号:
23K15383 - 财政年份:2023
- 资助金额:
$ 18.48万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of adverse effects of combined exposure to low-dose chemicals in the living environment on allergic diseases and attempts to reduce allergy
阐明生活环境中低剂量化学品联合暴露对过敏性疾病的不良影响并尝试减少过敏
- 批准号:
23H03556 - 财政年份:2023
- 资助金额:
$ 18.48万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Green tea-based nano-enhancer as an adjuvant for amplified efficacy and reduced adverse effects in anti-angiogenic drug treatments
基于绿茶的纳米增强剂作为抗血管生成药物治疗中增强疗效并减少不良反应的佐剂
- 批准号:
23K17212 - 财政年份:2023
- 资助金额:
$ 18.48万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Effects of Tobacco Heating System on the male reproductive function and towards to the reduce of the adverse effects.
烟草加热系统对男性生殖功能的影响以及减少不利影响。
- 批准号:
22H03519 - 财政年份:2022
- 资助金额:
$ 18.48万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Mitigating the Adverse Effects of Ultrafines in Pressure Filtration of Oil Sands Tailings
减轻油砂尾矿压力过滤中超细粉的不利影响
- 批准号:
563657-2021 - 财政年份:2022
- 资助金额:
$ 18.48万 - 项目类别:
Alliance Grants
1/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
1/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10521849 - 财政年份:2022
- 资助金额:
$ 18.48万 - 项目类别:
4/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
4/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10671022 - 财政年份:2022
- 资助金额:
$ 18.48万 - 项目类别:
2/4 Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
2/4 ECT 结果和不良反应的破译机制(DECODE)
- 批准号:
10670918 - 财政年份:2022
- 资助金额:
$ 18.48万 - 项目类别:
Adverse Effects of Using Laser Diagnostics in High-Speed Compressible Flows
在高速可压缩流中使用激光诊断的不利影响
- 批准号:
RGPIN-2018-04753 - 财政年份:2022
- 资助金额:
$ 18.48万 - 项目类别:
Discovery Grants Program - Individual