Repair and regeneration of osteochondral defects in mouse articular joints
小鼠关节骨软骨缺损的修复与再生
基本信息
- 批准号:1133883
- 负责人:
- 金额:$ 31.11万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-09-01 至 2016-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
1133883WeiIn a high percentage of patients, damages to the articular cartilage surface and the underlying subchondral bone can easily progress to joint degeneration, especially osteoarthritis which is the main cause of chronic disability in US. Extensive efforts have been made in osteochondral defect treatment, but there is still no widely accepted method which produces consistent satisfactory results. The regenerated cartilage is inferior to the original cartilage morphologically, biochemically, and biomechanically. Instead of forming articular cartilage, fibrocartilage is normally generated, which lacks of the long-term stability and cannot withstand prolonged stress to the joint. Thus, there is a need for a new approach that outperforms currently used methods. In this study, we propose to develop a graded scaffold with structure and mechanical properties mimicking those of natural cartilage, load the scaffold with articular-specific chondroprogenitor cells identified by GFP reporters, and then implant the cell-loaded scaffold into a novel transgenic mouse cartilage model to test for osteochondral repair and regeneration. It is expected that an optimum cell-scaffold construct will be determined which effectively regenerates osteochondral cartilage with excellent functionality and long-term stability.Intellectual merits: The novelty of the current proposal includes: (1) the development of a graded scaffold with structure, orientation, composition and mechanical properties mimicking those of natural cartilage and subchondral bone; (2) the development of an in-depth understanding of chondrocytes differentiation pathways and establishment of their lineage interrelationships; (3) the identification of articular-specific chondroprogenitor cells using a series of cartilage GFP reporters; (4) the development of an informative transgenic murine cartilage model to assess osteochondral repair and its integration with host tissues at a relatively low cost.Broader impact: The proposed project has a broader impact on various scientific disciplines. The results of the proposed research will contribute to our understanding of the cell-scaffold interactions, chondrocyte differentiation pathways, and host/donor cell contribution to the articular cartilage restoration for the first time. The information gained here will be an essential ingredient in developing and interpreting tissue engineering strategies to determine the optimal scaffold design and source of progenitors, and whether a repair process is initiated from the host or donor. Distinguishing the completeness of the repair in terms of the composition of cells that fill the repair region will be another measure of success of a repair strategy. The proposed research will be transformative to the tissue engineering field as it directly addresses the existing problems of the osteochondral cartilage repair and its approach may provide an effect solution to these problems.This project will result in the training of a graduate student and a number of undergraduate students in areas of tissue engineering, while exposing them to a multidisciplinary working environment. Efforts will be made to recruit female and minority students by integrating our research activities with existing recruiting efforts at the Department, the School and the University levels as well as participating in activities organized by various professional societies dedicated to underrepresented minorities. In addition, we will perform K-12 outreach to get high school students, especially female and underrepresented minorities, excited about engineering research. The results obtained from the project will be disseminated broadly via publishing in scientific journals, presenting in conferences and publicizing to general public via a website. We will make sure that all data will be kept for at least three years after conclusion of the award or three years after public release, whichever is later. We will also make our transgenic mice available to the tissue engineering community so that more researchers can use them to optimize their repair strategies.
1133883 Wei在很大比例的患者中,关节软骨表面和底层软骨下骨的损伤很容易进展为关节退行性变,特别是骨关节炎,这是美国慢性残疾的主要原因。在骨软骨缺损的治疗方面已经做出了广泛的努力,但是仍然没有广泛接受的方法产生一致的满意结果。再生软骨在形态学、生物化学和生物力学上均劣于原始软骨。关节软骨通常不形成,而是生成纤维软骨,其缺乏长期稳定性并且不能承受对关节的长期应力。因此,需要一种优于当前使用的方法的新方法。在这项研究中,我们建议开发一种结构和机械性能模仿天然软骨的梯度支架,加载支架与关节特异性软骨祖细胞识别的GFP报告,然后植入细胞加载的支架到一个新的转基因小鼠软骨模型测试骨软骨修复和再生。预期将确定一种最佳的细胞-支架结构,其有效地再生具有优异功能性和长期稳定性的骨软骨软骨。智力上的优点:当前建议的新奇包括:(1)开发具有模仿天然软骨和软骨下骨的结构、取向、组成和机械性能的梯度支架;(2)深入了解软骨细胞分化途径并建立其谱系关系;(3)使用一系列软骨GFP报告基因鉴定关节特异性软骨祖细胞;(4)开发信息丰富的转基因小鼠软骨模型,以相对较低的成本评估骨软骨修复及其与宿主组织的整合。拟议的项目对各个科学学科产生了更广泛的影响。拟议的研究结果将有助于我们理解细胞-支架相互作用,软骨细胞分化途径,以及宿主/供体细胞对关节软骨修复的贡献。这里获得的信息将是开发和解释组织工程策略的重要组成部分,以确定最佳支架设计和祖细胞来源,以及修复过程是否从宿主或供体开始。根据填充修复区域的细胞的组成来区分修复的完整性将是修复策略成功的另一个衡量标准。该研究将直接解决骨软骨修复中存在的问题,并为这些问题提供有效的解决方案,从而对组织工程领域产生变革性影响。该项目将培养一名研究生和多名本科生,同时将他们暴露在多学科的工作环境中。将努力招收女生和少数民族学生,办法是将我们的研究活动与系、学校和大学各级现有的招生工作相结合,并参加各种专业协会专门为代表人数不足的少数民族组织的活动。此外,我们将进行K-12外展,让高中学生,特别是女性和代表性不足的少数民族,对工程研究感到兴奋。项目取得的成果将通过在科学期刊上发表、在会议上介绍和通过网站向公众宣传而广泛传播。我们将确保所有数据将在奖项结束后或公开发布后至少保存三年,以较晚者为准。我们还将向组织工程界提供我们的转基因小鼠,以便更多的研究人员可以使用它们来优化修复策略。
项目成果
期刊论文数量(0)
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Mei Wei其他文献
Existence of positive S-asymptotically periodic solutions of the fractional evolution equations in ordered Banach spaces
有序Banach空间中分数阶演化方程正S-渐近周期解的存在性
- DOI:
10.15388/namc.2021.26.24176 - 发表时间:
2021-09 - 期刊:
- 影响因子:0
- 作者:
Qiang Li;Lishan Liu;Mei Wei - 通讯作者:
Mei Wei
Properties of Structured Tensors and Complementarity Problems
结构化张量的性质和互补问题
- DOI:
10.1007/s10957-020-01631-y - 发表时间:
2020-02 - 期刊:
- 影响因子:1.9
- 作者:
Mei Wei;Yang Qingzhi - 通讯作者:
Yang Qingzhi
Clinical characteristics and management of gastric outlet obstruction in acute pancreatitis
- DOI:
10.1016/j.pan.2020.11.010. - 发表时间:
2020 - 期刊:
- 影响因子:3.6
- 作者:
Cheng Qu;Xianqiang Yu;Zehua Duan;Jing Zhou;Wenjian Mao;Mei Wei;Longxiang Cao;Jingzhu Zhang;He Zhang;Lu Ke;Zhihui Tong;Weiqin Li - 通讯作者:
Weiqin Li
南岸低気圧とそれに伴う降水現象の予測可能性
南海岸气旋和相关降水现象的可预测性
- DOI:
- 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
Kamae Youichi;Mei Wei;Xie Shang-Ping;荒木健太郎 - 通讯作者:
荒木健太郎
Upper bounds for eigenvalues of Cauchy-Hankel tensors
Cauchy-Hankel 张量特征值的上限
- DOI:
10.1007/s11464-021-0890-0 - 发表时间:
2021-06 - 期刊:
- 影响因子:0
- 作者:
Mei Wei;Yang Qingzhi - 通讯作者:
Yang Qingzhi
Mei Wei的其他文献
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{{ truncateString('Mei Wei', 18)}}的其他基金
PFI:AIR - TT: Scale-up and Prototyping of Novel Scaffold Fabrication for Bone Regeneration
PFI:AIR - TT:用于骨再生的新型支架制造的放大和原型制作
- 批准号:
2002879 - 财政年份:2020
- 资助金额:
$ 31.11万 - 项目类别:
Standard Grant
Symposium BM3, Biomaterials for Regenerative Medicine
研讨会 BM3,再生医学生物材料
- 批准号:
1638492 - 财政年份:2016
- 资助金额:
$ 31.11万 - 项目类别:
Standard Grant
PFI:AIR - TT: Scale-up and Prototyping of Novel Scaffold Fabrication for Bone Regeneration
PFI:AIR - TT:用于骨再生的新型支架制造的放大和原型制作
- 批准号:
1639914 - 财政年份:2016
- 资助金额:
$ 31.11万 - 项目类别:
Standard Grant
PFI:AIR-TT: Prototyping bioabsorbable composites for bone-fixation applications involving low to medium loads
PFI:AIR-TT:用于低至中等负载骨固定应用的生物可吸收复合材料原型
- 批准号:
1414274 - 财政年份:2014
- 资助金额:
$ 31.11万 - 项目类别:
Standard Grant
EAGER: Fabrication of self-powered scaffolds for enhanced bone repair
EAGER:制造自供电支架以增强骨修复
- 批准号:
1347130 - 财政年份:2013
- 资助金额:
$ 31.11万 - 项目类别:
Standard Grant
I-Corps: Novel apatite/collagen scaffolds for bone repair
I-Corps:用于骨修复的新型磷灰石/胶原支架
- 批准号:
1243455 - 财政年份:2012
- 资助金额:
$ 31.11万 - 项目类别:
Standard Grant
GOALI: Multi-functional composites for load-bearing skeletal applications
GOALI:用于承重骨骼应用的多功能复合材料
- 批准号:
0503315 - 财政年份:2005
- 资助金额:
$ 31.11万 - 项目类别:
Continuing Grant
Collaborative Research: A Novel Approach to Improve the Interfacial Strength of Hydroxyapatite Coated Implants for Orthopedic and Dental Applications
合作研究:提高骨科和牙科应用羟基磷灰石涂层植入物界面强度的新方法
- 批准号:
0500269 - 财政年份:2005
- 资助金额:
$ 31.11万 - 项目类别:
Standard Grant
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