Bone Regeneration Induced by the Sustained Release of Osteoinductive microRNAs from 3D-printed Constructs

3D 打印结构中持续释放骨诱导性 microRNA 诱导骨再生

• 批准号: 10311132
• 负责人: Matthew T Remy
• 金额: $ 4.14万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-03 至 2023-07-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10311132
• 关键词: 3-Dimensional; 3D Print; Advanced Development; Adverse effects; Allografting; Architecture; Autologous Transplantation; Biocompatible Materials; Biodegradation; Biological; Biological Assay; Biology; Biomedical Engineering; Bone Development; Bone Morphogenetic Proteins; Bone Regeneration; Bone Transplantation; Calvaria; Cell Differentiation process; Cell-Matrix Junction; Cells; Clinic; Clinical; Clinical Treatment; Complex; Data; Defect; Development; Dimensions; Dose; Essential Genes; Extracellular Matrix; FDA approved; Family; Fellowship; Gelatin; Gene Expression; Goals; Growth; Hybrids; Implant; In Vitro; Infiltration; Investigation; Medicine; Methods; MicroRNAs; Nuclear; Nutrient; Organ Transplantation; Orthopedics; Osteogenesis; Patients; Polymers; Porosity; Positioning Attribute; Production; Property; Proteins; Rattus; Research; Research Training; Signal Transduction; Stains; Structure; Technology; Testing; Time; Tissue Engineering; Tissues; Transcript; Work; bone; bone marrow mesenchymal stem cell; bone metabolism; caprolactone; cell motility; clinical application; clinical translation; clinically relevant; crosslink; density; design; in vivo; in vivo regeneration; individualized medicine; innovation; insight; member; migration; multidisciplinary; new technology; novel; osteogenic; prevent; regeneration potential; regenerative; replacement tissue; restoration; scaffold

Project Summary/Abstract: Large bone defects are clincially challenging to treat and often necessitate bone grafting. Natural grafting options include autografts and allografts; however, these replacement tissues are limited in supply and difficult to match to the dimensional irregularities of complex bone defects. The development of tissue-engineered (TE) synthetic grafts has become essential to overcome the limitations of natural grafts; however, deficient scaffold fabrication methods and inefficient osteoinductive agents have prevented the clinical translation of traditional TE constructs. Therefore, the design of advanced synthetic grafts that overcome these limitations would greatly impact the clinical treatment of large bone defects. The long-term goal of this proposed work is to develop biodegradable, 3D-printed constructs with osteoconductive and inductive properties toward clinical use for the treatment of patient-specific bone defects. The objective of this proposal aims to develop a TE construct for bone regeneration using a hybrid materials approach that includes both synthetic and natural polymers in the 3D-printed structure, combined with the sustained release of osteoinductive microRNAs. Advanced TE constructs for this investigation will combine 3D-printable, FDA-approved polymers with tunable biodegradation rates with natural polymer coatings to sustain the release of osteoinductive microRNAs. The central hypothesis of this work is that the sustained release of osteoinductive microRNAs from polymer-coated 3D-printed constructs will enhance the osteogenic capabilities of synthetic grafts by prolonging regenerative signaling to maximize bone regeneration. To test this hypothesis, we will characterize microRNA release from polymer- coated 3D-printed constructs (Aim 1), assess in vitro osteogenic differentiation induced by microRNA release from polymer-coated constructs (Aim 2), and evaluate the bone regeneration potential of polymer-coated microRNA-incorporated 3D-printed constructs (Aim 3). Collectively, these data with elucidate mechanisms in which microRNA release from polymer-coated 3D-printed scaffolds can be optimized to sustain the release of osteoinductive signals and maximize bone regeneration. These results will advance the development of synthetic TE constructs to include both osteoconductive and inductive properties that will effectively promote bone regeneration, and thus significantly impact the clinical treatment of challenging, patient-specific bone defects.

项目摘要/摘要： 大骨缺损在治疗方面具有挑战性，通常需要骨移植。天然嫁接 选项包括自体移植和同种异体移植物；但是，这些替代组织的供应量有限，困难 与复杂骨缺损的维度不规则相匹配。组织工程（TE）的发展 合成移植物已成为克服天然移植物的局限性至关重要的。但是，脚手架不足 制造方法和效率低下的骨诱导剂阻止了传统的临床翻译 TE结构。因此，克服这些限制的高级合成移植物的设计将 极大地影响了大骨缺损的临床治疗。这项拟议工作的长期目标是 开发具有骨传导和感应特性的可生物降解的3D打印构建体 用于治疗患者特异性骨缺损。该提案的目的旨在开发一个结构 用于使用混合材料方法的骨再生，其中包括合成和天然聚合物 3D打印的结构，结合了骨诱导microRNA的持续释放。高级TE 该研究的构建体将结合3D打印的FDA批准聚合物与可调节的生物降解 天然聚合物涂层的速率维持骨诱导microRNA的释放。中心假设 这项工作是从聚合物涂层的3D打印中持续释放骨诱导的microRNA 构建体将通过延长再生信号传导来增强合成移植物的成骨功能 最大化骨骼再生。为了检验这一假设，我们将表征从聚合物中释放microRNA 涂层的3D打印构建体（AIM 1），评估MicroRNA诱导的体外成骨分化 从聚合物涂层的构建体（AIM 2），评估聚合物涂层的骨再生潜力 与MicroRNA合并的3D打印结构（AIM 3）。总的来说，这些数据具有阐明机制 可以优化从聚合物涂层的3D打印脚手架中释放的microRNA，以维持释放 骨诱导信号并最大化骨再生。这些结果将推动发展的发展 合成TE构建体以包括骨电导性和电感特性，这些特性将有效地促进 骨骼再生，从而显着影响具有挑战性的患者骨骼的临床治疗 缺陷。