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

• 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
• 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

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 在美国，颅面创伤导致每年超过1000万的急诊室就诊，这造成了巨大的社会影响。 经济负担。与小的缺损不同，由创伤性撕脱伤或 病理性病变切除需要有计划的重建或二次手术以恢复骨愈合。然而这些 缺陷不能自发愈合，被称为“临界尺寸缺陷”（CSD）。尝试诱导骨 血管化自体移植物的形成导致供体部位发病率和低收获量。此外，本发明还 重组人骨形态发生蛋白（rhBMP-2）生长因子与自体移植物一起使用， 手术后的有害炎症和肿胀。或者，钛（Ti）固定板提供结构支撑 但缺乏加速愈合的生物活性。此外，临床上可用的介孔BioglassTM， FDA批准的聚合物或复合糊剂或油灰缺乏骨愈合所需的强度和生物活性。 我们的目标是生物工程新的生物材料，目标是快速修复缺损的愈合机制。骨愈合 需要致密的生物矿物和血管组织的快速再生，这取决于抗氧化活性， 通过间充质干细胞（MSC）促进细胞迁移和成骨，通过内皮细胞促进血管生成， 细胞（EC）。我们的目标是通过（1）揭示靶向MSC的生物材料化学， 和EC抗氧化活性（2）原子层这些生物材料作为钛器械上的涂层， 缺陷愈合;以及（3）使用嵌入生物聚合物支架中的新纳米颗粒（NPs）化学物质， 缺陷愈合采用化学气相沉积法制备了氮氧磷化硅（SiONPx）涂层 用于释放抗氧化剂离子（Si 4+）的生物聚合物支架中的钛网和纳米颗粒（SiONPx-np）。我们 假设SiONPx通过增强骨愈合和血管组织愈合促进致密骨和血管组织愈合以及快速骨修复 抗氧化活性，以促进血管生成和骨生成。在目标1中，我们将研究Si 4+对 促进这些抗氧化剂在MSC成骨和EC血管生成。在目标2中，我们将确定 SiONPx涂层刺激抗氧化促进剂加速局部骨愈合环境的作用。 在目标3中，我们将使用SiONPx-np-生物聚合物支架来刺激抗氧化促进剂，以促进细胞增殖。 迁移、血管生成和骨生成进入支架结构以加速愈合过程。 我们的核心创新是开发一类新的可植入和可打印材料， 加速颅面骨缺损的愈合。一旦此类材料/器械在临床上可用， 是一个重大的进步，将已取得的承诺，对他们的翻译病人需要 大骨缺损或骨折的快速愈合。这些结果将对支持未来的发展产生积极影响。 在生物医学设备上进行新的抗氧化材料的临床试验，可以减少患者的愈合时间， 医疗保健成本，并提高大缺损处新形成骨的质量。