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

目标 作为一种有前途的替代传统的手术修复大的上颌骨和下颌骨缺损， 同种异体骨和自体骨，我们提出了依赖于内源性细胞的非活体3D打印骨移植物， 的患者。通常用于骨缺损，同种异体移植物在体内的能力有限， 骨细胞定植，特别是对于大的骨缺损。本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损，并定制制造 通过3D生物打印，特定的受控释放选择的生长， 因子和细胞因子。 方法 为了实现这一目标，理查德·L. Roudebush VAMC提供临床3D成像和计算机辅助 设计，结合新创建的3DTissue Bioprinting Core中可用的最先进技术 实验室，配备了regenHU 3DDiscovery 'Evolution'生物打印机。 第一个具体目标将是通过创建患者特定上颌骨的模型来生成此类结构。 和下颌骨缺损，然后用我们生物打印机上的软件，精确匹配移植物。 将使用三磷酸钙/羟基磷灰石支架作为结构组分绘制这些模型， 和作为生物活性组分的含有释放生长因子的微珠的水凝胶。 第二个具体目标将是通过评估以下动力学来体外测试该构建体的生物活性： 生长因子的释放和确定其诱导细胞募集和分化的能力。 如果成功，该项目将通过改进技术， 骨植入物的生物相容性和组织工程，适用于颌面部，腭裂和 许多其他骨骼修复的例子遍布全身--所有这些都是战斗重建中常见的 癌症治疗造成的伤害和缺陷。 随访研究（非本研究） 该项目包含几个创新的方法：一个双粘贴水凝胶打印，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 首先进行优化，然后开始下一项研究，该研究将探索一种精心设计的系统方法， 生长因子、细胞因子和骨移植支架的最佳组合。这将迅速和更多 有效地导致最终快速和更容易地转化为临床使用的大型动物模型

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