3D Printing bone graft containing controlled-release growth factors and cytokines

含有控释生长因子和细胞因子的 3D 打印骨移植物

• 批准号: 10731348
• 负责人: Clark T. Barco
• 金额: --
• 依托单位: RLR VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10731348
• 关键词: 3-Dimensional; 3D Print; Afghanistan; Allografting; Animal Model; Area; Autologous; Autologous Transplantation; BMP2 gene; Bone Regeneration; Bone Transplantation; Cell Differentiation process; Cell Mobility; Cells; Cleft Palate; Clinical; Complex; Computer Models; Computer software; Computer-Aided Design; Cost Savings; Custom; Data; Defect; Dental; Engineering; Event; Evolution; Face; Failure; Follow-Up Studies; Fracture; Freedom; Generations; Geometry; Goals; Growth Factor; Human; Hydrogels; Hydroxyapatites; Implant; In Vitro; Injury; Iraq; Joints; Kinetics; Laboratories; Lead; Left; Malignant Neoplasms; Mandible; Maxilla; Methods; Microspheres; Modeling; Modification; Movement; Nature; Neck Injuries; Operating Rooms; Operative Surgical Procedures; Oral; Oral mucous membrane structure; Outcome; Paste substance; Patients; Penetration; Porosity; Printing; Procedures; Process; Registries; Rehabilitation therapy; Reporting; Research; Series; Site; Source; Stromal Cell-Derived Factor 1; Supporting Cell; Surgeon; System; Technology; Testing; Thick; Three Dimensional Medical Imaging; Three-Dimensional Image; Three-Dimensional Imaging; Time; Tissue Engineering; Tissue Expanders; Tooth Extraction; Translations; Trauma; Vascular Endothelial Growth Factors; alveolar cleft; biomaterial compatibility; bioprinting; bone; bone cell; bone engineering; bone imaging; bone scaffold; cancer therapy; combat injury; combat wound; computer program; cone-beam computed tomography; controlled release; cost; cytokine; design; disease transmission; improved; in vitro Model; in vitro testing; in vivo; innovation; mandible/maxilla; manufacture; maxillofacial; operation; reconstruction; recruit; release factor; repaired; scaffold; skeletal; standard of care; success; tricalcium phosphate; virtual; wounded service member

Objectives As a promising alternative to the traditional surgical repair of large maxillary and mandibular defects with allograft and autologous bone, we propose non-vital, 3D printed bone grafts that rely on the endogenous cells of the recipient patient. Commonly used for osseous defects, allograft has a limited capacity for in vivo colonization with bone cells, especially for large osseous defects. This study proposes to develop and test in vitro osteoinductive porous grafts, pre-designed to fit the patients-specific defects, and custom manufactured specifically to the patient to be grafted, by 3D bioprinting with specific controlled-release of selected growth factors and cytokines. Methods To this goal, Richard L. Roudebush VAMC offers expertise in clinical 3D imaging and computer-assisted design, combined with the state-of-the-art technology available in newly created 3DTissue Bioprinting Core laboratory, equipped with a regenHU 3DDiscovery ‘Evolution’ bioprinter. The first Specific Aim will be the generation of such constructs by creating models of patient-specific maxillary and mandibular bone defects and then of their precisely fitting grafts, using the software on our bioprinter. These models will be plotted using as structural component a calcium triphosphate/hydroxyapatite scaffold, and as bioactive component a hydrogel containing growth factors-releasing microbeads. The second Specific Aim will be the in vitro testing of this construct’s bioactivity, by assessing the kinetics of growth factors release and by determining its ability to induce cell recruitment and differentiation. If successful, this project will stand by itself by generation of an improved technology for rapid, personalized and biocompatible tissue engineering of bone implants, with applicability to maxillofacial, cleft palate and many other instances of skeletal repair throughout the body – all are common with reconstruction of combat injuries and defects from cancer treatments. Follow-Up Study (not this study) This project contains several innovative approaches: a dual paste-hydrogel printing, addition of growth factors in microbeads within the hydrogel, testing intra-construct cell mobility and differentiation -- all will need to be first optimized before beginning the next study that will explore an elaborate systematic method of finding the best combination of growth factors, cytokines, and scaffolding for bone grafts. This will rapidly and much more efficiently lead to large animal models for an eventual rapid and easier translation to clinical use

目标 作为大小上颌和下颌缺陷的传统手术修复的承诺替代方案 同种异体移植和自体骨，我们提出了依赖内源细胞的非重要的3D印刷骨移植物 接受者患者。同种异体通常用于骨缺陷，体内的能力有限 用骨细胞定植，特别是对于大骨缺损。这项研究的提议开发和测试 体外骨诱导的多孔移植物，预先设计以适合患者特异性缺陷和定制制造 专门针对要嫁接的患者，通过3D生物打印和特定的受控生长释放 因素和细胞因子。 方法 为了实现这一目标，Richard L. Roudebush VAMC提供了临床3D成像和计算机辅助方面的专业知识 设计，再加上最新创建的3Dissue Bioprinting Core的最先进技术 实验室，配备了Regenhu 3DDISCOVERY的“ Evolution” Bioprointer。 第一个具体目的是通过创建特定于患者的上颌模型来产生此类构造 以及下颌骨缺损，然后是其精确拟合的移植物，使用我们的生物生产商上的软件。 这些模型将用作结构成分三磷酸钙/羟基磷灰石支架， 作为生物活性成分，含有释放生长因子的微粒的水凝胶。 第二个具体目的是通过评估该构建体的生物活性的体外测试，通过评估动力学 生长因子释放并确定其诱导细胞募集和分化的能力。 如果成功的话，该项目将通过生成一项改进的技术来实现快速，个性化的 和骨头的生物相容性组织工程，适用于上颌面，left裂和 整个身体的许多其他骨骼修复实例 - 所有这些都经常进行战斗的重建 癌症治疗的伤害和缺陷。 后续研究（不是这项研究） 该项目包含几种创新方法：双重糊状凝胶印刷，增长因子的增加 在水凝胶内的微珠中，测试结构内细胞的迁移率和分化 - 所有这些都需要是 首先在开始下一项研究之前进行了优化，该研究将探讨一种精心的系统方法 生长因子，细胞因子和骨移植的脚手架的最佳组合。这将迅速而越来越多 有效地导致大型动物模型快速，更轻松地转化为临床使用