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

项目总结/摘要 在创伤、肿瘤切除、先天性畸形、骨缺损和骨缺损的情况下， 畸形或由于拔牙或牙周病引起的骨吸收。目前，自体骨移植， 这与供体部位发病率和感染的风险增加有关， 需要额外的去除程序的膜是处理的标准。因此 本研究的目的是开发3D打印支架，用于临床上使用的颅面骨增量。 相关材料，脱矿骨基质，用于引导骨再生。对此的基本假设 研究项目是，在脱矿物质中发现的骨再生的内源性生化信号， 骨基质与通过3D打印调整支架微结构和交联的能力相结合， 改善骨质增生 为实现本项目的目标，将研究两个具体目标。在第一个具体目标中，我们 将制造由不同孔径的脱矿骨基质纳米颗粒组成的3D打印支架 和UV交联时间。然后将这些支架的机械性能和降解动力学进行比较。 通过压缩测试、体积溶胀和质量损失研究表征。此外，体外成骨细胞 将使用间充质干细胞评价脱矿骨基质支架的潜力， 通过碱性磷酸酶表达、钙含量和成骨分化标志物测量。的 这一特定目标的结果将阐明孔径和UV交联在确定成骨细胞中的作用， 脱矿骨基质支架的潜力，并确定哪些组适合于体内 翻译.在第二个具体目标中，我们将研究体内骨诱导和骨传导能力 3D打印的脱矿骨基质支架。支架将被植入大鼠顶骨 增强模型12周，并通过显微CT和组织学评估新形成的骨体积， 最大骨高度和骨质量。 完成上述工作后，我们将确定体外和体内骨再生 脱细胞、3D打印脱矿骨基质支架的功效和支架的可调节性 机械性能和降解。此外，拟议的工作提供了新的见解理性的3D- 用于颅面应用的印刷支架设计和制造。

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.