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 牙槽骨是牙齿和牙种植体固位的关键组织。增加牙槽骨质量， 由于牙周病或创伤而失去这种组织的患者对于成功的牙科植入至关重要 治疗（例如，在植入物放置之前拔牙部位周围的骨损失）。目前，骨移植 (e.g.,髂骨或下颌骨）或人造骨移植物通常用于牙槽骨再生 疗法然而，这些疗法中的大多数需要广泛的外科手术，这存在许多风险。 并发症，尤其是老年患者。因此，发展新的牙槽骨再生 迫切需要不需要外科手术的技术。在这项研究中，我们的目标是 开发一种可注射和仿生的高度多孔的微球为基础的治疗愈合的关键- 大小的牙槽骨缺损。我们最近开发了一种令人兴奋的方法， 由短的静电纺丝微球片段组成的微球，而不限于某些微球。 组合物的细胞可以在这种微球的表面上附着和增殖。与博士合作 Reinhardt（Co-I），我们还证明了与E7-BMP-2结合的矿化短纳米纤维 肽显示出治愈大鼠上颌骨中产生的临界尺寸的牙槽缺损模型的希望， 拔除第一磨牙。此外，我们最近的研究表明，BMP-2/QK肽 偶联微球能显著促进骨髓成骨分化 骨髓间充质干细胞与人脐静脉内皮细胞的管状网络形成 （HUVEC）。基于这些发现，假设可注射的高度多孔的生物相容性聚合物， 微球与信号分子的仿生递送和/或BMSC的掺入的组合 能大大促进牙槽骨再生后，微创给药到临界大小 大鼠牙槽骨缺损。为了验证假设并实现主要目标，我们的策略是 三重：i）展示具有受控组成的多孔微球的制造， 结构和信号分子的偶联; ii）检查工程化多孔聚合物的效果， 具有仿生递送信号分子的微球对细胞应答的影响;和iii）确定骨 可注射多孔微球的再生能力与仿生递送的组合 信号分子和/或BMSC用于大鼠牙槽骨缺损的愈合。我们希望找出关键的 仿生和可注射的高度多孔纳米纤维微球疗法的因素有助于 牙槽骨再生同时，我们期望这些目标的顺利完成，为 开发可注射的骨移植物，可以大大加速牙槽骨缺损的愈合， 侵入性外科手术