Citrate Metabonegenic Regulation for the next Generation of Orthopedic Biomaterial Design

下一代骨科生物材料设计的柠檬酸代谢调节

基本信息

批准号：
10364767
负责人：
Jian Yang
金额：
$ 34.07万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10364767
关键词：
5&apos -AMP-activated protein kinase Address Anatomy Animal Model Animals Architecture Biocompatible Materials Biomimetics Bone Development Bone Matrix Bone Regeneration Bone Tissue Cell Culture Techniques Cells Cellular Metabolic Process Cephalic Chemicals Chronic Citrates Complex Consumption Crystallization Defect Development Developmental Process Energy Metabolism FRAP1 gene Implant Inflammation Inflammatory Response Knowledge Mechanics Mediating Mesenchymal Differentiation Mesenchymal Stem Cells Metabolic Minerals Modeling Molecular Orthopedics Osteoblasts Osteogenesis Pathway interactions Performance Phenotype Physiology Play Process Protein Biosynthesis Protein Kinase Proteins Rattus Regulation Research Role Signal Transduction Skeletal system Testing Tissue Engineering Tissues Translating base bone bone repair design extracellular in vivo mimetics mineralization next generation novel osteogenic scaffold stem cell differentiation stem cells uptake

项目摘要

Research Summary The objectives of this project are to elucidate an unexplored metabonegenic regulation of citrate for bone development, and to translate these understandings towards the design of novel biomimetic citrate-presenting bone biomaterials for orthopedic applications. Although significant progress has been made in the development of orthopedic biomaterials, the currently available materials are limited by their inabilities to mimic the native tissue composition, weak mechanical strength, minimal osteoinductivity, significant inflammatory responses, poor bone integration, and slow bone regeneration. We hypothesize that the uptake of extracellular citrate via transporter SLC13a5 could elevate cellular energy status through modulation of cell metabolism, which in turn leads to a facilitated osteogenic phenotype progression by inhibiting the activity of AMP-activated protein kinase (AMPK). This new citrate-based regulation of bone development is referred to as citrate metabonegenic regulation (Fig. 1). The identification of new and unexplored citrate-based strategies to promote osteogenic differentiation of mesenchymal stem cell can be harnessed to more efficiently design the next generation of biomimetic orthopedic biomaterials to address the limitations of the previous materials. To test our hypotheses and achieve the objectives of this project, three aims are proposed: Aim 1) to elucidate the metabonegenic regulatory effect of citrate for MSCs osteogenic differentiation; Aim 2) to apply the understandings of the citrate molecular mechanism in the design of biomimetic citrate-presenting biomaterials to mediate MSCs differentiation; Aim 3) To evaluate the in vivo performance of anatomically and chemically mimetic citrate-presenting scaffolds in a rat critically sized cranial bone defect model. It is very intriguing that the unprecedented knowledge on the unexplored citrate mechanism will enable us to design the next generation of biomimetic dynamic orthopedic implants that may present citrate signals in demand during cellular and tissue development. The understanding on the citrate metabonegenic regulation for bone stem cell culture and dynamic bone materials design will not only advance the field of bone tissue engineering, but also profoundly impact a wide array of other conditions such as MSC adipogenic differentiation since MSCs is multipotent and the adipogenic differentiation also has high energy demand.

研究摘要该项目的目的是阐明柠檬酸盐的未开发的变质。开发，并将这些理解转化为新型仿生柠檬酸盐的设计用于骨科应用的骨生物材料。尽管在骨科生物材料的开发，当前可用的材料受模仿的无能为力的限制天然组织组成，机械强度弱，骨诱导率最小，炎症明显反应，骨骼整合不良和缓慢的骨骼再生。我们假设细胞外的吸收柠檬酸盐通过转运蛋白SLC13A5可以通过调节细胞代谢，可以提升细胞能量状态，这反过蛋白激酶（AMPK）。这种新的基于柠檬酸盐的骨骼发育调节称为柠檬酸盐变质的调节（图1）。确定新的和未开发的基于柠檬酸盐的策略可以利用促进间充质干细胞的成骨分化，以更有效地设计下一代仿生骨科生物材料以解决先前材料的局限性。到检验我们的假设并实现该项目的目标，提出了三个目标：目标1）阐明柠檬酸盐对MSC成骨分化的变质调节作用；目标2）应用柠檬酸分子机制的理解在仿生柠檬酸盐呈现生物材料的设计中介导MSC分化；目标3）评估解剖学和化学上的体内性能大鼠大小的颅骨缺损模型中的模仿柠檬酸盐呈乳酸酯。这很有趣关于未开发的柠檬酸盐机制的前所未有的知识将使我们能够设计下一个产生可能在需求中呈现柠檬酸盐信号的仿生动态骨科植入物细胞和组织发育。对骨干细胞柠檬酸盐代纳牛的理解的理解培养和动态骨料设计不仅会推进骨组织工程领域，还会推进深刻影响各种各样的其他条件，例如MSC掺杂分化，因为MSC为多能和掺杂分化也具有较高的能量需求。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Citrate-based fluorometric sensor for multi-halide sensing.

DOI：
10.1016/j.smaim.2022.05.001
发表时间：
2022
期刊：
Smart materials in medicine
影响因子：
0
作者：
Wang, Dingbowen;Xia, Tunan;Wang, Yuqi;Chen, Yizhu;Zhang, Chenji;Murray, William;Schultz, Adam Thomas;Liu, Zhiwen;Yang, Jian
通讯作者：
Yang, Jian

Angiogenic hydrogels for dental pulp revascularization.

DOI：
10.1016/j.actbio.2021.03.001
发表时间：
2021-05
期刊：
Acta biomaterialia
影响因子：
9.7
作者：
Siddiqui Z;Sarkar B;Kim KK;Kadincesme N;Paul R;Kumar A;Kobayashi Y;Roy A;Choudhury M;Yang J;Shimizu E;Kumar VA
通讯作者：
Kumar VA

Novel Metal Nanomaterials to Promote Angiogenesis in Tissue Regeneration.