3D-Printed Demineralized Bone Matrix Hydrogels for Craniofacial Bone Tissue Regeneration.

3D 打印脱矿骨基质水凝胶用于颅面骨组织再生。

• 批准号: 10261420
• 负责人: Katie Hogan
• 金额: $ 4.68万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-09 至 2023-09-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10261420
• 关键词: 3D Print; Alkaline Phosphatase; Architecture; Autologous Transplantation; Biochemical; Biocompatible Materials; Blood Vessels; Bone Matrix; Bone Regeneration; Bone Resorption; Bone Tissue; Calcium; Cells; Cleft Palate; Clinical; Complex; Congenital Abnormality; Cues; Dental; Dental Implantation; Devices; Disease; Ensure; Excision; Extracellular Matrix; Geometry; Goals; Growth Factor; Height; Histology; Hydrogels; Implant; In Vitro; Infection; Kinetics; Lead; Measures; Membrane; Mesenchymal Differentiation; Mesenchymal Stem Cells; Modeling; Morbidity - disease rate; Natural regeneration; Operative Surgical Procedures; Parietal bone structure; Patients; Periodontal Diseases; Porosity; Procedures; Property; Rattus; Research; Research Project Grants; Risk; Role; Site; Swelling; Testing; Time; Tissue Engineering; Tissues; Tooth Diseases; Tooth Extraction; Translations; Trauma; Work; alveolar bone; bone; bone quality; clinically relevant; craniofacial; craniofacial bone; craniofacial tissue; crosslink; demineralization; density; design; hydrogel scaffold; improved; in vivo; in vivo Model; in vivo regeneration; infection rate; insight; mechanical properties; microCT; nanoparticle; osteogenic; palate repair; reconstruction; scaffold; standard care; stem cell proliferation; tissue regeneration; tumor

Project Summary/Abstract There is a clinical need for craniofacial bone augmentation in cases of trauma, tumor resection, congenital malformations, or bone resorption as a result of tooth extraction or periodontal disease. Currently, bone autograft, which is associated with increased risk of donor site morbidity and infection, and non-resorbable barrier membranes, which required additional procedures for removal, are the standard of treatment. Therefore, the objective of this research is to develop 3D printed scaffolds for craniofacial bone augmentation using a clinically relevant material, demineralized bone matrix, for guided bone regeneration. The fundamental hypothesis for this research project is that the endogenous biochemical cues for bone regeneration found within demineralized bone matrix combined with the ability to tune scaffold microarchitecture and crosslinking via 3D printing will result in improved bone augmentation. Two specific aims will be investigated to accomplish the goals of this project. In the first specific aim, we will fabricate 3D-printed scaffolds composed of demineralized bone matrix nanoparticles with varied pore sizes and UV crosslinking times. The mechanical properties and degradation kinetics of these scaffolds will then be characterized via compressive testing, bulk swelling, and mass loss studies. Additionally, the in vitro osteogenic potential of the demineralized bone matrix scaffolds will be evaluated using mesenchymal stem cells and measured by alkaline phosphatase expression, calcium content, and markers of osteogenic differentiation. The results of this specific aim will elucidate the role of pore size and UV crosslinking in determining the osteogenic potential of demineralized bone matrix scaffolds and determine which groups are appropriate for in vivo translation. In the second specific aim, we will investigate the in vivo osteoinductive and osteoconductive capacity of 3D-printed demineralized bone matrix scaffolds. The scaffolds will be implanted in a rat parietal bone augmentation model for 12 weeks and assessed via micro-CT and histology for newly formed bone volume, maximum bone height, and bone quality. Upon completion of the proposed work, we will have determined the in vitro and in vivo bone regeneration efficacy of an acellular, 3D-printed demineralized bone matrix scaffold and demonstrated tunability of scaffold mechanical properties and degradation. Additionally, the proposed work provide new insights into rational 3D- printed scaffold design and fabrication for craniofacial applications.

项目摘要/摘要 在创伤，肿瘤切除术，先天性的情况下，临床需要增加颅面骨骼 牙齿拔牙或牙周疾病导致的畸形或骨吸收。目前，骨自体移植， 这与供体现场发病率和感染的风险增加以及不可用的障碍有关 膜需要额外去除程序，是治疗的标准。因此， 这项研究的目的是开发3D打印的支架，用于使用临床 相关的材料，脱矿质的骨基质，用于引导骨再生。为此的基本假设 研究项目是在脱矿物中发现的骨再生的内源性生化提示 骨基质结合了通过3D打印来调整脚手架微体系结构和交联的能力 在改善骨骼增强中。 将研究两个具体目标以实现该项目的目标。在第一个特定目标中，我们 将制造由脱矿物基质纳米颗粒组成的3D打印支架，孔径变化 和紫外线交联的时间。这些脚手架的机械性能和降解动力学将是 通过压缩测试，散装肿胀和质量流失研究来表征。另外，体外成骨 将使用间充质干细胞和 通过碱性磷酸酶的表达，钙含量和成骨分化的标志物测量。这 该特定目标的结果将阐明孔径和紫外线交联在确定成骨中的作用 脱矿质骨基质支架的潜力，并确定哪些组适合体内 翻译。在第二个特定目的中，我们将研究体内骨诱导和整骨的能力 3D打印的非矿化骨基质支架。脚手架将植入大鼠顶骨 增强模型12周，并通过Micro-CT和组织学评估新形成的骨体积， 最大骨高和骨质质量。 提议的工作完成后，我们将确定体外和体内骨再生 细胞，3D打印的脱矿质骨基质支架的功效，并证明了脚手架的可调性 机械性能和降解。此外，拟议的工作为理性3D-提供了新的见解 用于颅面应用的印刷脚手架设计和制造。