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： 大骨缺损的临床治疗具有挑战性，通常需要骨移植。自然嫁接 选项包括自体移植和同种异体移植；然而，这些替代组织的供应有限且困难 以匹配复杂骨缺损的尺寸不规则性。组织工程（TE）的发展 合成移植物对于克服天然移植物的局限性至关重要；但脚手架不足 制造方法和低效的骨诱导剂阻碍了传统骨诱导剂的临床转化 TE 构建。因此，克服这些限制的先进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 开发具有骨传导和诱导特性的可生物降解的 3D 打印结构，供临床使用 用于治疗患者特定的骨缺损。该提案的目标是开发 TE 结构 使用混合材料方法进行骨再生，其中包括合成和天然聚合物 3D 打印的结构与骨诱导性 microRNA 的持续释放相结合。高级TE 这项研究的结构将结合可 3D 打印、FDA 批准的聚合物和可调节的生物降解能力 天然聚合物涂层的速率可维持骨诱导性 microRNA 的释放。中心假设 这项工作的重点是从聚合物涂层的 3D 打印材料中持续释放骨诱导性 microRNA 结构将通过延长再生信号来增强合成移植物的成骨能力 最大限度地促进骨再生。为了检验这一假设，我们将表征从聚合物中释放的 microRNA 涂层 3D 打印结构（目标 1），评估 microRNA 释放诱导的体外成骨分化 来自聚合物涂层结构（目标 2），并评估聚合物涂层的骨再生潜力 掺入 microRNA 的 3D 打印结构（目标 3）。总的来说，这些数据阐明了机制 可以优化聚合物涂层 3D 打印支架中的 microRNA 释放，以持续释放 骨诱导信号并最大化骨再生。这些成果将推动我国的发展 合成 TE 结构包括骨传导和诱导特性，可有效促进 骨再生，从而显着影响具有挑战性的患者特异性骨的临床治疗 缺陷。