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 颅面骨扩大术在创伤、肿瘤切除、先天性畸形等方面有临床需求。 因拔牙或牙周病而导致的畸形或骨吸收。目前，自体骨移植， 这与供区发病率和感染风险增加以及不可吸收屏障有关。 膜是治疗的标准，需要额外的程序才能去除。因此， 本研究的目的是开发3D打印支架，用于颅面骨增强的临床应用。 相关材料，脱钙骨基质，用于引导骨再生。对此的基本假设是 研究项目是在内源性生化线索中发现的骨再生脱矿 骨基质与调整支架微体系结构和通过3D打印进行交联的能力相结合将产生 在改善骨骼增强方面。 为实现该项目的目标，将研究两个具体目标。在第一个具体目标中，我们 将制作由不同孔径的脱钙骨基质纳米颗粒组成的3D打印支架 和紫外光交联时间。然后这些支架的力学性能和降解动力学将被 通过压缩测试、体积膨胀和质量损失研究来表征。此外，体外成骨细胞 脱钙骨基质支架的潜力将使用间充质干细胞和 通过碱性磷酸酶表达、钙含量和成骨分化标志物进行测量。这个 这一特定目的的结果将阐明孔径大小和紫外线交联度在确定成骨作用中的作用。 脱钙骨基质支架的潜力和确定哪些组适合体内 翻译。在第二个具体目标中，我们将研究体内的骨诱导和骨传导能力。 3D打印的脱矿骨基质支架。支架将被植入大鼠的顶骨中 植入模型12周，通过显微CT和组织学检查新生骨体积， 最大骨高度和骨质量。 当建议的工作完成后，我们将确定体外和体内骨再生。 脱细胞3D打印脱钙骨基质支架的有效性和可调整性 力学性能和降解。此外，拟议的工作为Rational3D提供了新的见解- 用于颅面应用的印刷支架的设计和制造。