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.

项目总结 牙槽骨是牙齿和种植体固位的关键组织。牙槽骨骨量增加 由于牙周疾病或创伤而失去这些组织的患者是成功种植牙齿的关键 治疗(例如，种植体植入前拔牙部位周围的骨质丢失)。目前，骨移植 (例如，髂骨或下颌骨)或人工骨移植通常用于牙槽骨再生。 心理治疗。然而，这些疗法中的大多数都需要广泛的外科手术，这带来了许多风险 并发症，特别是老年患者。因此，新牙槽骨再生的发展 迫切需要不需要外科手术的技术。在此，在这项拟议的研究中，我们的目标是 为了开发一种可注射和仿生的高度多孔的纳米纤维微球疗法，用于治愈危重患者- 大小的牙槽骨缺损处。我们最近开发了一种令人兴奋的方法来制造仿生材料 由短电纺纳米纤维片段组成的纳米纤维微球，不限于某些 作文。细胞可以在这种纳米纤维微球的表面附着和增殖。与Dr. Reinhardt(Co-I)，我们还证明了矿化短纳米纤维与E7-BMP-2结合 多肽显示出修复大鼠上颌骨临界大小的眼窝缺损模型的希望，如下所示 拔除第一颗磨牙。此外，我们最新的研究表明，BMP-2/QK多肽 共轭纳米纤维微球可显著促进骨髓向成骨细胞分化 间充质干细胞与人脐静脉内皮细胞的管网形成 (HUVEC)。基于这些发现，推测可注射的高度多孔纳米纤维 微球与信号分子的仿生传递和/或骨髓间充质干细胞的掺入 对临界大小的牙槽骨微创给药后可大大促进牙槽骨再生 大鼠牙槽骨缺损的实验研究。为了验证假设并实现主要目标，我们的策略是 三个方面：i)展示了具有可控组成的多孔纳米纤维微球的制备， 结构和信号分子的偶联；ii)检测工程多孔纳米纤维的效果 具有仿生递送信号分子的微球对细胞的响应；以及iii)确定骨骼 可注射多孔纳米纤维微球结合仿生递送的再生能力 修复大鼠牙槽骨缺损的信号分子和/或骨髓间充质干细胞。我们希望确定关键的 基于仿生和可注射的高孔纳米纤维微球治疗的因素 牙槽骨再生。此外，我们期待着这些目标的成功完成，为 开发可注射骨移植，可极大地促进牙槽骨缺损的愈合 侵入性外科手术。