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: 10053065
• 负责人: SUSMITA BOSE
• 金额: $ 35.08万
• 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/10053065
• 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.

抽象的 修订后的 R01 申请旨在使用天然药物化合物 (NMC) 来增强生物活性 的合成骨移植物。在合成骨移植物中输送 NMC，例如磷酸钙 (CaP) 支架，对于调节骨细胞-材料相互作用以改善体内成骨和 血管生成。我们建议使用 NMC 来研究骨诱导性 3D 打印 (3DP) CaP 骨移植物 在骨科和牙科应用中不使用任何生长因子（GF）或蛋白质。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。我们建议使用姜黄素等 NMC 来自姜黄、来自芦荟的乙酰甘露聚糖以及维生素 D3 等必需营养素，可改善 Caps 中的骨整合而不是使用 GF。在我们的初步研究中，我们看到了有希望的结果 由于 NMC 的存在，显示出血管生成和骨生成增强。我们发现 姜黄素可以增强 3DP CaP 支架的成骨和血管生成。从我们之前的工作来看，我们 还确定在 CaP 中添加 Mg2+、Si4+、Zn2+ 和 Ag+ 等掺杂剂可以改善 机械性能，增强成骨和血管生成，同时改善抗菌反应 体内。结合我们关于 NMC 的令人兴奋的初步结果和掺杂剂化学的既定数据，我们 提议展示下一代合成骨移植物，不含任何 GF 或蛋白质，用于以下领域的应用 牙科和骨科，这是本应用的前提。 本研究的目的是检验我们的中心假设，即负载 NMC 的掺杂 CaP 多孔 3D 打印（3DP）支架将增强体内成骨和血管生成特性。理由是，一旦 我们了解不同 NMC 所需的剂量、它们的释放动力学以及骨细胞的机制- 材料相互作用调节，关键知识差距，我们可以设计无GF合成骨移植物 临床应用与自体移植类似。我们的长期目标是证明临床相关的患者 匹配的成骨和血管生成掺杂的 CaP 或 CaP-聚合物支架与 NMC，将替代 用于骨科和牙科修复、替换和增强的自体骨。为了实现我们的 针对研究目标，我们提出了两个具体目标。目标 1 侧重于了解 NMC 的影响 增强多孔 CaP 陶瓷和陶瓷聚合物复合支架的体外生物活性。目标 2 是 专注于使用负载 NMC 的多孔 CaP 陶瓷测量体内成骨和血管生成 陶瓷-聚合物复合支架。如果成功的话，NMC 还可以与其他材料一起用于牙科和 骨科应用。