DNA-Hyaluronic Acid Platform for Spatiotemporally Probing the Role of Adhesion Ligands on BMP-Induced Osteogenesis In Vitro

DNA-透明质酸平台用于时空探索粘附配体对 BMP 诱导体外成骨作用的作用

• 批准号: 9899918
• 负责人: Julianne Leigh Holloway
• 金额: $ 15.19万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9899918
• 关键词: Adhesions; Behavior Control; Binding; Binding Proteins; Biocompatible Materials; Biology; Bone Morphogenetic Proteins; Bone Regeneration; Cell Adhesion; Cell Culture Techniques; Cell Proliferation; Cell-Cell Adhesion; Cell-Matrix Junction; Cells; Chemistry; Clinical; Complementary DNA; Complex; Custom; DNA; Data; Development; Dose; Drug Delivery Systems; Environment; Extracellular Matrix; Fluorescent Dyes; Future; Glycosaminoglycans; Growth Factor; Hyaluronic Acid; Hydrogels; Immobilization; In Vitro; Kinetics; Knowledge; Ligands; Linker DNA; Literature; Mediating; Medical; Methods; Mind; Molecular; N-Cadherin; Natural regeneration; Osteogenesis; Peptides; Polymers; Production; Proteins; Reaction; Research; Research Personnel; Role; Scheme; Signal Pathway; Signal Transduction; Signaling Molecule; Skeletal Development; Skeletal bone; System; Therapeutic; Time; Tissue Engineering; Tissues; Work; arginyl-glycyl-aspartyl-serine; base; bone growth factor; bone morphogenetic protein 2; chemical reaction; design; extracellular; healing; improved; migration; novel; peptidomimetics; prevent; programs; scaffold; spatiotemporal; stem cell niche; stem cells; synergism; time use; tissue regeneration

Project Summary Advances in tissue engineering have been limited, in part, due to challenges in controlling the biomolecule signals important for regeneration. In particular, tissue engineering approaches for bone repair have been inhibited by the supraphysiological doses of the growth factor bone morphogenetic protein-2 (BMP-2) required for adequate healing due to suboptimal delivery. In the native extracellular matrix (ECM), BMP-2 is tightly bound by proteins and glycosaminoglycans with its presentation regulated in space and time to enhance bioactivity. Furthermore, researchers have shown significant synergies with other signaling molecules, such as cell-matrix or cell-cell adhesion ligands. To mimic these interactions, a number of elegant approaches based on photopatterning and orthogonal chemistries have been developed for presenting biomolecules. However, these approaches rely on highly customized chemical reactions (which may be difficult to implement with multiple classes of biomolecules) and are generally restricted to 1-2 signals. They are also often based on photocleavage reactions for temporal control, which precludes their reversibility over multiple cycles. Given the complexity of the extracellular environment (e.g. the stem cell “niche”) in controlling the fate of cells, a general in vitro platform that can control three or more signals, as well as multiple types of biomolecules, in both space and time would be invaluable for teasing apart the factors that control behavior like cell proliferation, migration, differentiation, and new tissue formation. We propose to develop a biomaterial-based in vitro platform capable of independently, and reversibly, controlling the spatiotemporal presentation of the growth factor bone morphogenetic protein-2 (BMP-2) in combination with the RGDS peptide to mimic cell-matrix adhesion and the HAVDI peptide to mimic cell-cell adhesion. Thus, the specific aims of the work are: (1) Investigate the temporal effect of immobilized BMP-2 on osteogenesis and (2) Determine the spatiotemporal role of cell-cell and cell- matrix interactions during BMP-2-induced osteogenesis.

项目概要 组织工程的进展受到限制，部分原因是控制生物分子方面的挑战 对再生很重要的信号。特别是用于骨修复的组织工程方法 受到所需的生长因子骨形态发生蛋白 2 (BMP-2) 的超生理剂量的抑制 由于分娩不理想而导致充分愈合。在天然细胞外基质 (ECM) 中，BMP-2 紧密结合 与蛋白质和糖胺聚糖结合，其表达在空间和时间上受到调节，以增强 生物活性。此外，研究人员还显示出与其他信号分子的显着协同作用，例如 细胞-基质或细胞-细胞粘附配体。为了模仿这些交互，许多优雅的方法基于 已经开发了光图案化和正交化学来呈现生物分子。然而， 这些方法依赖于高度定制的化学反应（这可能很难用 多类生物分子）并且通常仅限于 1-2 个信号。它们也常常基于 用于时间控制的光裂解反应，这排除了它们在多个循环中的可逆性。鉴于 细胞外环境（例如干细胞“生态位”）在控制细胞命运方面的复杂性，一般 可以在两个空间中控制三个或更多信号以及多种类型的生物分子的体外平台 时间对于梳理控制细胞增殖、迁移等行为的因素是非常宝贵的。 分化和新组织形成。我们建议开发一个基于生物材料的体外平台 独立且可逆地控制生长因子骨的时空呈现 形态发生蛋白 2 (BMP-2) 与 RGDS 肽结合模拟细胞基质粘附和 HAVDI 肽模拟细胞间粘附。因此，这项工作的具体目标是：（1）调查时间 固定化 BMP-2 对成骨的影响以及 (2) 确定细胞-细胞和细胞-的时空作用 BMP-2 诱导的成骨过程中基质相互作用。

项目成果

Using dynamic biomaterials to study the temporal role of bioactive peptides during osteogenesis.

• DOI: 10.1016/j.bioadv.2023.213726
• 发表时间: 2023-12
• 期刊: Biomaterials advances
• 作者: Fallon M. Fumasi;T. MacCulloch;J. Bernal-Chanchavac;N. Stephanopoulos;Julianne L. Holloway