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

项目摘要 在美国，颅面创伤每年导致超过1000万急诊室就诊，造成巨大的社会- 经济负担。与小缺陷不同的是，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性愈合。然而，这些 缺陷不会自发愈合，因此被称为“临界尺寸缺陷”(CSD)。诱导成骨的尝试 血管化自体移植物的形成导致供体部位发病率和低采集量。此外， 重组人骨形态发生蛋白(RhBMP2)生长因子与自体移植一起使用经常产生 手术后有害的炎症和肿胀。或者，钛(钛)固定板提供结构支撑 骨碎片，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，目标是快速修复缺陷的修复机制。骨愈合 需要快速再生致密的生物矿物和血管组织，这取决于抗氧化活性 间充质干细胞促进细胞迁移和成骨，内皮促进血管生成 细胞(EC)。我们的目标是通过(1)揭示以间充质干细胞为靶点的生物材料化学来促进骨愈合 和EC抗氧化活性(2)原子化地将这些生物材料作为涂层覆盖在钛设备上以增强骨骼 修复缺陷；以及(3)使用嵌入生物聚合物支架中的新纳米颗粒(NPs)化学成分快速 缺陷愈合。采用化学气相沉积法制备了氮化硅膜 用于释放抗氧化剂离子(Si4+)的生物聚合物支架中的钛网状和纳米颗粒(SiONPx-NP)。我们 假设SiONPx增强致密骨和血管组织愈合和快速骨修复 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+对离子交换的影响。 这些抗氧化剂在MSCs成骨和ECs血管生成过程中的促进作用。在目标2中，我们将确定 SiONPx涂层具有刺激抗氧化剂促进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启动子来促进细胞 向支架结构迁移、血管生成和成骨，以加速愈合过程。 我们的主要创新是开发一种新型的可植入和可打印的材料，它可以 加速颅面骨缺损的愈合。一旦这样的材料/设备可以在临床上使用， 是承诺将在翻译方面取得重大进展，以帮助有需要的患者 大的骨缺陷或骨折的快速愈合。这些结果将对未来的支持产生积极的影响 新型抗氧化材料在生物医疗设备上的临床试验可以缩短患者的愈合时间，减少 医疗成本，提高了大面积缺损区新骨形成的质量。

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.