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: 10275493
• 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/10275493
• 关键词: 3-Dimensional; 3D Print; Afghanistan; Allografting; Animal Model; Area; Autologous; Autologous Transplantation; BMP2 gene; Bone Regeneration; Bone Transplantation; Calcium; 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; 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; base; 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; maxillofacial; operation; reconstruction; recruit; release factor; repaired; scaffold; skeletal; standard of care; success; tripolyphosphate; 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 作为传统手术修复大型上颌骨和下颌骨缺损的有前景的替代方案 同种异体骨和自体骨，我们提出依赖内源细胞的非生命3D打印骨移植物 通常用于治疗骨缺损，同种异体移植物的体内能力有限。 骨细胞的定植，特别是对于大的骨缺损，本研究建议进行开发和测试。 体外骨诱导多孔移植物，预先设计以适合患者特定的缺陷，并定制制造 通过 3D 生物打印，对选定的生长物进行特定的控释，专门针对要移植的患者 因子和细胞因子。 方法 为了实现这一目标，Richard L. Roudebush VAMC 提供临床 3D 成像和计算机辅助方面的专业知识 设计，结合新创建的 3DTissue 生物打印核心中最先进的技术 实验室，配备了 regenHU 3DDiscovery“Evolution”生物打印机。 第一个具体目标是通过创建患者特定上颌骨模型来生成此类结构 和下颌骨缺损，然后使用我们生物打印机上的软件精确匹配移植物。 这些模型将使用三磷酸钙/羟基磷灰石支架作为结构成分进行绘制， 以及作为生物活性成分的含有生长因子释放微珠的水凝胶。 第二个具体目标是通过评估该构建体的动力学来体外测试该构建体的生物活性 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，该项目将通过产生改进的技术来独立实现快速、个性化的 骨植入物和生物相容性组织工程，适用于颌面、腭裂和 全身骨骼修复的许多其他实例——所有这些都在战斗重建中很常见 癌症治疗造成的伤害和缺陷。 后续研究（不是本研究） 该项目包含多种创新方法：双浆料-水凝胶印刷、添加生长因子 在水凝胶内的微珠中，测试构建体内的细胞移动性和分化——所有这些都需要 在开始下一项研究之前首先进行优化，该研究将探索一种精细的系统方法来寻找 生长因子、细胞因子和骨移植支架的最佳组合这将快速且更多。 有效地产生大型动物模型，最终快速、更轻松地转化为临床使用