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.

项目概要 在美国，颅面外伤每年导致超过 1000 万人次到急诊室就诊，这造成了巨大的社会影响 与小缺陷不同，由创伤性撕脱伤或创伤引起的大的复杂缺陷。 然而，病理病变切除需要计划的重建或二次手术才能恢复骨性愈合。 缺陷不会自发愈合，被称为“临界尺寸缺陷”（CSD）。 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。 重组人骨形态发生蛋白 (rhBMP2) 生长因子与自体移植物一起使用通常会产生 另外，钛 (Ti) 固定板可提供结构支撑。 此外，临床上可用的介孔 BioglassTM， FDA 批准的聚合物、复合糊剂或油灰缺乏骨愈合所需的强度和生物活性。 我们的目标是通过生物工程设计新的生物材料，以快速修复骨缺损的愈合机制为目标。 需要致密的生物矿物质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) 促进细胞迁移和骨生成，通过内皮细胞促进血管生成 我们的目标是通过 (1) 揭示针对 MSC 的生物材料化学成分来刺激骨愈合。 和 EC 抗氧化活性 (2) 以原子方式将这些生物材料分层作为钛装置上的涂层，以增强骨骼 缺陷愈合；（3）使用嵌入生物聚合物支架的新型纳米颗粒（NP）化学物质来快速愈合 我们通过化学气相沉积创建了氧硝基磷化硅（SiONPx）作为新涂层。 用于生物聚合物支架中的钛网和纳米颗粒 (SiONPx-np)，释放抗氧化离子 (Si4+)。 研究发现 SiONPx 通过增强功能来增强致密骨和血管组织的愈合和快速骨修复 抗氧化活性促进血管生成和成骨 在目标 1 中，我们将研究 Si4+ 对血管生成和成骨的影响。 在目标 2 中，我们将确定这些抗氧化剂在 MSC 成骨和 EC 血管生成过程中的促进作用。 SiONPx 涂层可刺激抗氧化剂促进剂，加速局部骨愈合环境。 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促进细胞 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种新型可植入和可打印材料，该材料可以 一旦此类材料/设备投入临床使用，就会加速颅面骨缺损的愈合。 是承诺在将其翻译给需要治疗的患者方面将取得重大进展 大骨缺损或骨折的快速愈合这些结果将对支持未来产生积极影响。 新型抗氧化材料在生物医学设备上的临床试验可以缩短患者的愈合时间，减少 医疗护理成本，并提高大缺损处新形成骨的质量。