3D Printed Calcium Phosphate Scaffolds with Natural Medicinal Compounds for Dental Applications

用于牙科应用的含天然药用化合物的 3D 打印磷酸钙支架

• 批准号: 10220015
• 负责人: SUSMITA BOSE
• 金额: $ 35.12万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10220015
• 关键词: 3D Print; Aloe vera plant; Alveolar Ridge Augmentation; Anti-Inflammatory Agents; Arthritis; Autologous; Autologous Transplantation; Beds; Biocompatible Materials; Biological; Biological Availability; Biomimetics; Bone Diseases; Bone Regeneration; Bone Tissue; Bone Transplantation; Cells; Ceramics; Chelating Agents; Chemistry; Chemopreventive Agent; Cholecalciferol; Clinical; Clinical Research; Curcumin; Data; Defect; Dental; Dental Materials; Dentistry; Distal; Dose; Exhibits; FASTK Gene; Femur; Filler; Goals; Growth Factor; Harvest; Hydrophobicity; Immune response; Implant; In Vitro; Inflammation; Kinetics; Knowledge; Liposomes; Measures; Mechanics; Metals; Methods; Micelles; Modeling; Nutrient; Operative Surgical Procedures; Orthopedics; Oryctolagus cuniculus; Osseointegration; Osteoblasts; Osteoclasts; Osteogenesis; Patients; Performance; Polyethylene Glycols; Polymers; Porosity; Powder dose form; Property; Proteins; Rattus; Research; Role; Serum; Site; Spinal Fusion; Testing; Tissues; Titanium; Trace Elements; Tumeric; Weight-Bearing state; Work; absorption; angiogenesis; anti-cancer; antimicrobial; base; bone; bone cell; bone healing; bone health; calcium phosphate; clinical application; clinically relevant; design; healing; improved; in vivo; innovation; maxillofacial; mechanical properties; metabolic rate; next generation; osteoclastogenesis; osteogenic; polycaprolactone; practical application; preclinical study; reconstruction; repaired; response; scaffold

Abstract This revised R01 application aims to use natural medicinal compounds (NMCs) to enhance bioactivity of synthetic bone grafts. The delivery of NMCs in synthetic bone grafts, such as calcium phosphate (CaP) scaffolds, is critical to modulate bone cell-materials interactions to improve in vivo osteogenesis and angiogenesis. Using NMCs, we propose to investigate osteoinductive, 3D-Printed (3DP) CaP bone grafts without using any growth factors (GF) or proteins towards applications in orthopedics and dentistry. However, there still exists a clinical need to innovate osteoinductive synthetic resorbable biomaterials that will promote angiogenesis, exhibiting biological properties similar to autografts. We propose to use NMCs such as curcumin from turmeric, acemannan from aloe vera, and essential nutrients such as Vitamin D3 to improve osseointegration in CaPs instead of using GFs. In our preliminary studies, we have seen promising results showing angiogenesis and enhanced osteogenesis due to the presence of NMCs. We have found that curcumin can enhance osteogenesis and angiogenesis of 3DP CaP scaffolds. From our previous work, we have also established that addition of dopants such as Mg2+, Si4+, Zn2+ and Ag+ in CaP can improve mechanical properties, enhance osteogenesis and angiogenesis while improving antimicrobial response in vivo. Combining our exciting preliminary results on NMCs and established data on dopant chemistry, we propose to demonstrate next generation of synthetic bone grafts without any GF or proteins for applications in dentistry and orthopedics, which is the premise of this application. The objective of this research is to test our central hypothesis that NMC-loaded doped CaP porous 3D Printed (3DP) scaffolds will enhance osteogenic and angiogenic properties in vivo. The rationale is that once we understand the required dose for different NMCs, their release kinetics, and the mechanism of bone cell- materials interactions modulation, the key knowledge gaps, we can design GF free synthetic bone grafts similar to autografts in clinical applications. Our long-range goal is to demonstrate clinically relevant patient matched, osteogenic and angiogenic doped CaP or CaP– polymer scaffolds with NMCs that will substitute autologous bone for repair, replacement, and augmentation in orthopedics and dentistry. To achieve our research objectives, we propose two Specific Aims. Aim 1 is focused on understanding the influence of NMCs on enhanced bioactivity of porous CaP ceramic, and ceramic-polymer composite scaffolds in vitro. Aim 2 is focused on measuring osteogenesis and angiogenesis in vivo using NMC loaded porous CaP ceramic and ceramic-polymer composite scaffolds. If successful, NMCs can also work with other materials for dental and orthopedic applications.

摘要 此修订的R01应用程序旨在使用天然药物化合物(NMC)来增强生物活性 人造骨移植。人工骨中NMCs的释放，如磷酸钙(CaP) 支架是调节骨细胞-材料相互作用以促进体内成骨和 血管生成。使用NMC，我们建议研究骨诱导的3D打印(3DP)帽骨移植 不使用任何生长因子(GF)或蛋白质应用于整形外科和牙科。然而， 临床上仍然需要创新骨诱导合成可吸收生物材料，以促进 血管生成，表现出与自体移植物相似的生物学特性。我们建议使用非金属化合物，如姜黄素 从姜黄中提取，从芦荟中提取乙酰甘露聚糖，并补充维生素D3等必需营养素来改善 使用CAPS进行骨整合，而不是使用GFS。在我们的初步研究中，我们看到了有希望的结果。 显示由于NMC的存在，血管生成和增强的成骨作用。我们发现， 姜黄素可促进3DP帽状支架的成骨和血管生成。根据我们之前的工作，我们 我还证实，在帽子中添加镁、硅、锌和银等掺杂剂可以改善 力学性能，促进成骨和血管生成，同时改善抗菌反应 活着。结合我们在NMC上令人振奋的初步结果和关于掺杂化学的既定数据，我们 建议展示不含任何GF或蛋白质的下一代合成骨移植在 牙科和整形外科，这是这一应用的前提。 这项研究的目的是检验我们的中心假设，即NMC负载的掺杂帽多孔3D 打印(3DP)支架将增强体内的成骨和血管生成特性。理由是，一旦 我们了解不同的NMC所需的剂量，它们的释放动力学，以及骨细胞的机制- 材料相互作用调制，关键知识空白，我们可以设计不含GF的人工骨 与自体移植在临床上的应用类似。我们的长期目标是证明与临床相关的患者 匹配的、成骨的和血管生成的掺杂帽或帽-聚合物支架与NMC将取代 骨科和牙科中用于修复、替换和增强的自体骨。为了实现我们的目标 研究目标方面，我们提出了两个具体目标。目标1侧重于了解NMC的影响 关于提高多孔帽陶瓷和陶瓷-聚合物复合支架的体外生物活性。目标2是 重点研究了使用NMC负载的多孔帽陶瓷和在体骨形成和血管生成 陶瓷-聚合物复合支架。如果成功，NMC还可以与其他材料一起用于牙科和 整形外科的应用。