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

基本信息

批准号：
10450826
负责人：
SUSMITA BOSE
金额：
$ 34.72万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
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/10450826
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 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 bone repair 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

项目摘要

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.

抽象的此修订后的R01应用程序旨在使用天然医学化合物（NMC）来增强生物活性合成骨移植物。 NMC在合成骨移植物中的递送，例如磷酸钙（CAP）脚手架，对于调节骨细胞材料相互作用至关重要，以改善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）盖骨移植不使用任何生长因子（GF）或蛋白质用于骨科和牙科中的应用。然而，仍然存在创新骨诱导合成可吸收生物材料的临床需求，以促进血管生成，表现出类似于自体移植的生物学特性。我们建议使用姜黄素等NMC 从姜黄，芦荟的acemannan和维生素D3等必需营养素来改善 ossecometration in Caps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由于NMC的存在，显示出血管生成和增强的成骨。我们发现姜黄素可以增强3DP帽支架的成骨和血管生成。从我们以前的工作中，我们还确定添加掺杂剂，例如mg2+，si4+，zn2+和ag+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。结合我们在NMC上令人兴奋的初步结果，并建立了有关掺杂化学的数据，我们提出证明下一代合成骨移植的建议，而没有任何GF或蛋白质用于应用牙科和骨科，这是本申请的前提。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 印刷（3DP）支架将在体内增强成骨和血管生成特性。理由是一次我们了解不同NMC的所需剂量，它们的释放动力学以及骨细胞的机理材料互动调制，关键知识差距，我们可以设计GF免费合成骨移植类似于临床应用中的自体移植。我们的远程目标是展示与临床相关的患者与NMC相匹配的，成骨和血管生成的掺杂帽或盖 - 聚合物支架骨科和牙科中的自体骨可修复，置换和增强。实现我们的研究目标，我们提出了两个具体目标。 AIM 1专注于理解NMC的影响在体外的多孔帽陶瓷和陶瓷聚合物复合材料支架的生物活性增强方面。 AIM 2是专注于使用NMC负载的多孔帽陶瓷和陶瓷聚合物复合支架。如果成功，NMC也可以与其他牙科材料一起使用，骨科应用。