Biomimetic and Injectable Highly Porous Nanofiber Microsphere-based Platform for Alveolar Bone Regeneration

用于牙槽骨再生的仿生和可注射高孔隙纳米纤维微球平台

• 批准号: 10641000
• 负责人: Jingwei Xie
• 金额: $ 53.37万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-08 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10641000
• 关键词: Acceleration; BMP2 gene; BMP5 gene; Binding; Binding Proteins; Biological; Biomimetics; Bone Diseases; Bone Regeneration; Bone Resorption; Bone Transplantation; Cell Fate Control; Cells; Coupled; Coupling; Data; Defect; Dental Implants; Development; Endothelial Cells; Engineering; Engraftment; Foundations; Gases; Human; Immobilization; Implantation procedure; Injectable; Injections; Mandible; Maxilla; Methods; Microspheres; Minerals; Modeling; Molar tooth; Morphology; Natural regeneration; Operative Surgical Procedures; Osteogenesis; Patients; Peptides; Periodontal Diseases; Play; Porosity; Proliferating; Proteins; Rattus; Receptor Cell; Regenerative capacity; Risk; Role; Signaling Molecule; Site; Structure; Surface; Surgical Flaps; Suspensions; Swelling; Techniques; Testing; Therapeutic; Tissues; Tooth Extraction; Tooth Tissue; Trauma; Tubular formation; Umbilical vein; Vascular Endothelial Growth Factors; Vascularization; aged; alveolar bone; angiogenesis; bone; bone healing; bone loss; bone marrow mesenchymal stem cell; bone mass; bone prosthesis; clinically relevant; cost; fabrication; healing; mineralization; minimally invasive; nanofiber; osteogenic; peptidomimetics; receptor; recombinant human bone morphogenetic protein-2; regenerative; regenerative therapy; repaired; response; side effect; stem cells; technology platform

PROJECT SUMMARY Alveolar bone is a critical tissue for tooth and dental implant retention. Increasing alveolar bone mass in patients who lose this tissue as a result of periodontal disease or trauma is crucial for successful dental implant therapy (e.g., loss of bone around a tooth extraction site prior to implant placement). Currently, bone grafts (e.g., iliac or mandibular bone) or artificial bone grafts are commonly used for alveolar bone regeneration therapy. However, most of these therapies require extensive surgical procedures, which present risks of many complications, particularly in aged patients. Therefore, the development of new alveolar bone regeneration techniques that do not require surgical procedures is urgently needed. Herein, in this proposed study, we aim to develop an injectable and biomimetic highly porous nanofiber microsphere-based therapy for healing critical- sized alveolar bone defects. We recently developed an exciting approach for the fabrication of biomimetic nanofiber microspheres consisting of short electrospun nanofiber segments without limitation to certain compositions. Cells can attach and proliferate on the surface of such nanofiber microspheres. Working with Dr. Reinhardt (Co-I), we also demonstrated that mineralized short nanofibers incorporated with E7-BMP-2 peptides showed promise for healing a critical-sized socket defect model created in rat maxillae, following extraction of the first molar teeth. In addition, our most recent study revealed that BMP-2/QK peptides conjugated nanofiber microspheres can significantly enhance osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and tubular network formation of human umbilical vein endothelial cells (HUVECs). Based on these findings, it is hypothesized that the injectable highly porous nanofiber microspheres in combination with biomimetic delivery of signaling molecules and/or incorporation of BMSCs could greatly promote alveolar bone regeneration after minimally invasive administration to critical-sized alveolar bone defects in rats. To test the hypothesis and accomplish the primary objective, our strategy is three-fold: i) Demonstrate the fabrication of porous nanofiber microspheres with controlled composition, structure, and coupling of signaling molecules; ii) Examine the effect of engineered porous nanofiber microspheres with biomimetic delivery of signaling molecules on cellular response; and iii) Determine the bone regenerative capacity of injectable porous nanofiber microspheres in combination with biomimetic delivery of signaling molecules and/or BMSCs for healing alveolar bone defects in rats. We expect to identify the critical factors of biomimetic and injectable highly porous nanofiber microsphere-based therapy that contribute to alveolar bone regeneration. Also, we expect successful completion of these aims to lay the foundation for developing injectable bone grafts that could greatly accelerate healing of alveolar bone defects without invasive surgical procedures.

项目摘要 牙槽骨是牙齿和牙科植入物保留的关键组织。增加牙槽骨块 因牙周疾病或创伤而失去该组织的患者对于成功的牙科植入物至关重要 治疗（例如，植入植入物放置之前，牙齿拔牙部位周围失去骨骼）。目前，骨移植 （例如，i骨或下颌骨）或人造骨移植物通常用于肺泡骨再生 治疗。但是，这些疗法大多数都需要广泛的手术程序，这表现出许多人的风险 并发症，特别是在老年患者中。因此，新的肺泡骨再生的发展 迫切需要不需要手术程序的技术。在此，在这项拟议的研究中，我们的目标 开发可注射和仿生的高度多孔纳米纤维微球治疗，以治愈关键 大小的肺泡骨缺损。我们最近开发了一种令人兴奋的仿生制作方法 纳米纤维微球由短电纺纳米纤维段组成，而无需限制 组成。细胞可以在这种纳米纤维微球的表面附着并增殖。与博士合作 Reinhardt（Co-I），我们还证明了与E7-BMP-2合并的矿化短纳米纤维 肽显示出愈合临界大小的插座缺陷模型的希望 提取第一摩尔牙齿。此外，我们最近的研究表明BMP-2/QK肽 共轭纳米纤维微球可以显着增强骨髓的成骨分化 间充质干细胞（BMSC）和人脐静脉内皮细胞的管状网络形成 （HUVECS）。基于这些发现，可以假设注射高度多孔纳米纤维 微球与信号分子的仿生递送和/或BMSC结合 在最小侵入性给关键大小的侵入性后，可以极大地促进牙槽骨再生 大鼠牙槽骨缺损。为了检验假设并实现主要目标，我们的战略是 三倍：i）证明具有控制组成的多孔纳米纤维微球的制造， 信号分子的结构和偶联； ii）检查工程多孔纳米纤维的效果 微球具有信号分子在细胞反应上的仿生递送； iii）确定骨头 可注射多孔纳米纤维微球的再生能力与仿生递送的结合 信号分子和/或BMSC，用于愈合大鼠肺泡骨缺损。我们希望确定关键 仿生和可注射高度多孔纳米纤维微球的因素，有助于 肺泡骨再生。另外，我们希望成功完成这些目标，以奠定 开发可注射的骨移植物，可以极大地加速肺泡骨缺损的愈合 侵入性手术程序。