Semiconductor Biomaterials to Speed Bone Healing: A Bioengineering-Driven Approach

半导体生物材料加速骨骼愈合：生物工程驱动的方法

基本信息

批准号：
10587508
负责人：
Venu Gopal Varanasi
金额：
$ 47.95万
依托单位：
UNIVERSITY OF TEXAS ARLINGTON
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-03 至 2028-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10587508
关键词：
3-Dimensional ANGPT1 gene Acceleration Angiopoietins Antioxidants Autologous Autologous Transplantation Biocompatible Materials Biological Assay Biomaterials Research Biomedical Engineering Biopolymers Blood Vessels Bone Density Bone Growth Bone Matrix Bone Morphogenetic Proteins Bone Regeneration Bone Tissue Cells Cephalic Chemicals Chemistry Clinical Clinical Trials Collagen Complex Cysteine Data Defect Deposition Development Devices Economic Burden Electrons Emergency department visit Endothelial Cells Environment Enzyme-Linked Immunosorbent Assay Excision FDA approved Fracture Future GATA1 gene Gelatin General Population Goals Growth Factor Harvest Health Care Costs Histology Human Implant In Vitro Inflammation Injury Ions Lead Lesion Medical Care Costs Mesenchymal Stem Cells Methods Mission Morbidity - disease rate Morphology Musculoskeletal Natural regeneration Nitrogen Operative Surgical Procedures Osteocalcin Osteogenesis Paste substance Pathologic Patients Phosphorus Polymers Process Proteins Rattus Reaction Recombinants Rehabilitation therapy Research Research Personnel Roentgen Rays Scientist Semiconductors Signal Transduction Silicon Site Speed Stimulus Structure Swelling Testing Time Tissues Titanium Translating Translations Trauma United States National Institutes of Health Vascular Endothelial Cell Vascular Endothelial Growth Factors Vascularization angiogenesis biomaterial development bone bone healing bone repair cell motility clinically relevant craniofacial craniofacial bone density effective therapy fabrication healing hypoxia inducible factor 1 improved in vivo innovation migration nanocomposite nanoparticle nuclear factor-erythroid 2 osteogenic preclinical study promoter reconstruction repaired sample fixation scaffold socioeconomics stem cell differentiation vapor

3-Dimensional ANGPT1 gene Acceleration Angiopoietins Antioxidants Autologous Autologous Transplantation Biocompatible Materials Biological Assay Biomaterials Research Biomedical Engineering Biopolymers Blood Vessels Bone Density Bone Growth Bone Matrix Bone Morphogenetic Proteins Bone Regeneration Bone Tissue Cells Cephalic Chemicals Chemistry Clinical Clinical Trials Collagen Complex Cysteine Data Defect Deposition Development Devices Economic Burden Electrons Emergency department visit Endothelial Cells Environment Enzyme-Linked Immunosorbent Assay Excision FDA approved Fracture Future GATA1 gene Gelatin General Population Goals Growth Factor Harvest Health Care Costs Histology Human Implant In Vitro Inflammation Injury Ions Lead Lesion Medical Care Costs Mesenchymal Stem Cells Methods Mission Morbidity - disease rate Morphology Musculoskeletal Natural regeneration Nitrogen Operative Surgical Procedures Osteocalcin Osteogenesis Paste substance Pathologic Patients Phosphorus Polymers Process Proteins Rattus Reaction Recombinants Rehabilitation therapy Research Research Personnel Roentgen Rays Scientist Semiconductors Signal Transduction Silicon Site Speed Stimulus Structure Swelling Testing Time Tissues Titanium Translating Translations Trauma United States National Institutes of Health Vascular Endothelial Cell Vascular Endothelial Growth Factors Vascularization angiogenesis biomaterial development bone bone healing bone repair cell motility clinically relevant craniofacial craniofacial bone density effective therapy fabrication healing hypoxia inducible factor 1 improved in vivo innovation migration nanocomposite nanoparticle nuclear factor-erythroid 2 osteogenic preclinical study promoter reconstruction repaired sample fixation scaffold socioeconomics stem cell differentiation vapor

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项目摘要

Project Summary Craniofacial trauma leads to over 10 million emergency room visits per year in the US that cause a vast socio- economic burden. Unlike small defects, large complex defects arising from traumatic avulsive injuries or pathologic lesion resection require planned reconstruction or secondary surgery to regain bony union. Yet, these defects do not spontaneously heal and are known as “critical size defects” (CSD). Attempts to induce bone formation by vascularized autologous grafts led to donor site morbidity and low harvest volume. Further, recombinant human bone morphogenic protein (rhBMP2) growth factor used with autograft often produces harmful inflammation and swelling post-surgery. Alternatively, titanium (Ti) fixation plates lend structural support to bony fragments but lack bioactivity to speed healing. Moreover, clinically available mesoporous BioglassTM, FDA-approved polymers, or composite pastes or putties lack needed strength and bioactivity for bone healing. Our goal is to bioengineer new biomaterials that target healing mechanisms for rapid defect repair. Bone healing requires rapid regeneration of dense biomineral and vascular tissue, which depends on antioxidant activity to promote cell migration and osteogenesis by mesenchymal stem cells (MSC) and angiogenesis by endothelial cells (EC). Our objective is to stimulate bone healing by (1) revealing biomaterial chemistries that target MSC and EC antioxidant activity (2) atomistically layer these biomaterials as coatings on Ti devices to enhance bone defect healing; and (3) use new nanoparticles (NPs) chemistries embedded in biopolymer scaffolds for rapid defect healing. We created silicon oxy-nitro-phosphide (SiONPx) by chemical vapor deposition as new coatings for Ti mesh and nanoparticles (SiONPx-np) in biopolymer scaffolds that release antioxidant ions (Si4+). We hypothesize that SiONPx enhances dense bone and vascular tissue healing and rapid bone repair via enhanced antioxidant activity to promote angiogenesis and osteogenesis. In Aim 1, we will study the effect of Si4+ on the promotion of these antioxidants during MSCs osteogenesis and ECs angiogenesis. In Aim 2, we will determine the effect of SiONPx coatings to stimulate antioxidant promoters to hasten the local bone healing environment. In Aim 3, we will use SiONPx-np-biopolymer scaffolds to stimulate antioxidant promoters to promote cell migration, angiogenesis, and osteogenesis into scaffold structures to hasten the healing process. Our central innovation is the development of a new class of implantable and printable materials that can accelerate healing of craniofacial bone defects. Once such materials/devices become clinically available, there is the promise that a significant advancement will have been made toward their translation in patients needing rapid healing of large bone defects or fractures. These results will have a positive impact in supporting future clinical trials of new antioxidant materials on biomedical devices that can reduce patient healing time, reduce medical care cost, and increase the quality of newly formed bone in large defects.

项目摘要颅面创伤导致美国每年超过1000万次急诊室就诊，造成广泛的社会社会经济负担。与小缺陷不同，由创伤性侵袭性损伤或病变病变切除需要计划的重建或二级手术才能重新获得骨工会。但是，这些缺陷在赞助上没有治愈，被称为“临界大小缺陷”（CSD）。试图诱导骨头血管化自体移植物的形成导致供体部位的发病率和低收获体积。更远，自体移植使用的重组人骨形态学蛋白（RHBMP2）生长因子通常会产生手术后有害注射和肿胀。另外，钛（Ti）固定板借用结构支撑骨碎片，但缺乏生物活性的速度愈合。此外，临床上可用的介孔bioglasstm， FDA批准的聚合物或复合糊剂或推杆缺乏骨骼愈合的强度和生物活性。我们的目标是针对快速缺陷修复的生物工程新生物材料。骨骼愈合需要快速再生生物矿物质和血管组织，这取决于抗氧化活性促进间充质干细胞（MSC）的细胞迁移和成骨，内皮的血管生成细胞（EC）。我们的目的是通过（1）揭示针对MSC的生物材料化学物质来刺激骨骼愈合 EC抗氧化活性（2）原子上这些生物材料作为Ti设备上的涂层以增强骨骼缺陷愈合；（3）使用嵌入生物聚合物支架中的新纳米颗粒（NP）化学物质快速缺陷愈合。我们通过化学蒸气沉积作为新涂层创建对于释放抗氧化离子（SI4+）的生物聚合物支架中的Ti网格和纳米颗粒（Sionpx-NP）。我们假设sionpx通过增强来增强致密的骨骼和血管组织愈合以及快速修复抗氧化活性以促进血管生成和成骨。在AIM 1中，我们将研究Si4+对在MSCS成骨和EC血管生成过程中，这些抗氧化剂促进这些抗氧化剂。在AIM 2中，我们将确定 sionpx涂层刺激抗氧化剂启动子的影响加快了局部骨骼愈合的环境。在AIM 3中，我们将使用sionpx-np-biopomermater支架来刺激抗氧化剂启动子以促进细胞迁移，血管生成和成骨发生到脚手架结构中，以加快愈合过程。我们的中心创新是开发新的可植入和可打印材料，可以加速颅面骨缺损的愈合。一旦此类材料/设备在临床上可用，是否承诺将在患者需求中对他们的翻译取得重大进步大骨缺陷或骨折的快速愈合。这些结果将对支持未来产生积极影响在生物医学设备上的新抗氧化材料的临床试验，这些材料可以减少患者的愈合时间，减少医疗费用，并提高大缺陷中新形成的骨骼的质量。