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

目标 作为一种有希望的替代传统手术修复巨大的上颌骨和下颌骨缺损 同种异体骨和自体骨，我们提出了依赖内源性细胞的无生命3D打印骨移植。 接受治疗的病人。同种异体骨移植通常用于骨缺损，但体内移植的能力有限。 有骨细胞的定植，尤指大的骨缺陷。这项研究建议开发和测试 体外骨诱导多孔移植物，预先设计以适应患者特定的缺陷，并定制制造 通过3D生物打印和选定生长的特定受控释放，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，理查德·L·鲁德布什VAMC提供临床3D成像和计算机辅助方面的专业知识 设计，结合最新创建的3DTIssue Biopprint Core中可用的最先进技术 实验室，配备了一台regenHU 3D发现‘进化’生物打印机。 第一个具体目标将是通过创建针对患者的上颌骨模型来生成这样的结构 和下颌骨缺损，然后是他们的精确匹配的移植物，使用我们的生物打印机上的软件。 这些模型将使用三磷酸钙/羟基磷灰石支架作为结构组件绘制， 作为生物活性成分的水凝胶含有生长因子释放微球。 第二个具体目标将是体外测试这种结构的生物活性，通过评估动力学 生长因子的释放和决定其诱导细胞募集和分化的能力。 如果成功，这个项目将独立于一代快速、个性化的改进技术 和生物相容的骨组织工程，适用于颌面部、腭裂和 全身骨骼修复的许多其他例子--所有这些都是战斗重建中常见的 癌症治疗带来的伤害和缺陷。 随访研究(不是本研究) 该项目包含了几种创新的方法：双糊剂-水凝胶打印，添加生长因子 在水凝胶内的微珠中，测试结构内细胞的流动性和分化--所有这些都需要 在开始下一项研究之前首先进行优化，下一项研究将探索一种精细的系统方法来找到 生长因子、细胞因子和骨移植支架的最佳组合。这将迅速并远远超过 高效地建立大型动物模型，最终快速且更容易地转化为临床使用

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