Complex Nanocomposites for Bone Regeneration

描述（由申请人提供）：本生物工程研究伙伴关系提案由加州大学（UC）系统的多学科科学家合作提交。牵头机构是劳伦斯伯克利国家实验室，在加州大学伯克利分校和加州大学旧金山弗朗西斯科校区设有组成小组。该BRP汇集了材料科学，化学，生物学和牙科/医学科学的专业知识，开始该项目的转化阶段。我们的目标是开发用于组织工程的生物材料，以消除手术风险并允许立即恢复功能。我们将开发和测试新的植入材料，可以支持间充质干细胞和骨再生，通过结合仿生学与全新的设计理念，考虑解剖和功能需求，定制支架骨骼缺损。最终目标是开发一系列与周围天然组织协调功能的骨诱导植入材料或支架。这一长期目标将为颅面和骨科骨骼缺损的最佳修复提供材料，否则需要从第二个手术部位进行骨移植。首先，将合成具有不同机械响应和生物降解速率的水凝胶。不同的功能基团将被添加到水凝胶结构中，以模拟磷灰石和其他生物矿物的仿生矿化，并促进细胞粘附。第二，这些材料，以及其他已经为我们目前的资助开发的材料，将用于制备具有各种成分和结构的支架，包括解剖学灵感的设计，考虑通过robocasting（3D打印）和层状结构制成的皮质和松质骨功能解剖结构，该结构使用我们实验室开发的基于悬浮液冷冻铸造的新技术制备。第三，将系统地探索这些多孔支架的不同功能。将在细胞培养物中测试被认为显示最佳机械响应的材料，然后在小鼠体内使用标准化骨形成试验进行测试，该试验允许评估新骨形成的速率和程度。基于这些结果，我们将选择具有最大翻译潜力的支架。这些将与自体多能干细胞组合测试，以利用生物力学和生物测定的一致方案在已建立的中型（兔）和大型（小型猪）动物模型中促进骨形成的能力，所述生物力学和生物测定也将用于评估确定支架整合的关键生物过程。这些研究的成功完成将导致识别适合用于测试人类颅面和骨科骨骼缺损修复的新材料。目前对此类缺损的护理标准可能会有所改变，以消除骨移植物，降低患者风险，改善生活质量，并增加临床医生的医疗设备。

DESCRIPTION (provided by applicant): This Bioengineering Research Partnership proposal is submitted by a multidisciplinary collaboration of scientists in the University of California (UC) system. The lead institution is Lawrence Berkeley National Laboratory, with component groups at UC Berkeley and UC San Francisco campuses. This BRP brings together expertise in materials sciences, chemistry, biology, and dental/medical science to begin the translational phase of this project. Our goal is to develop biomaterials for tissue engineering that will eliminate surgical risks and allow immediate return of function. We will develop and test new implant materials that can support mesenchymal stem cells and bone regeneration, by combining biomimetics with radically new design philosophies that consider anatomic and functional needs, customizing the scaffold to the skeletal defect. The ultimate goal is to develop a range of osteoinductive implant materials or scaffolds that function harmoniously with the surrounding native tissue. This long-term goal will provide materials for optimal repair of craniofacial and orthopedic skeletal defects that would otherwise require a bone graft from a second surgical site. First, hydrogels with varying mechanical responses and biodegradation rates will be synthesized. Different functional groups will be added to the hydrogel structure to template biomimetic mineralization of apatite and other biominerals-and to promote cell adhesion. Second, these materials, and others already developed for our current grant, will be used in the preparation of scaffolds with various compositions and architectures, including anatomically-inspired designs that considers both cortical and cancellous functional anatomy made by robocasting (3-D printing) and lamellar structures prepared using a novel technology developed in our laboratory based on freeze-casting of suspensions. Third, the addition of diverse functional capabilities to these porous scaffolds will be systematically explored. Materials deemed to display optimal mechanical responses will be tested in cell culture and then in vivo in mice, using standardized bone formation assays that allow assessment of the rate and extent of new bone formation. Based on these results, we will select scaffolds that have the greatest translational potential. These will be tested in combination with autologous multipotent stem cells for the ability to promote bone formation in established medium-sized (rabbit) and large-sized (mini-pig) animal models utilizing a consistent protocol of biomechanical and biological assays that will also serve to asses key biological process that determine scaffold integration. Successful completion of these studies will result in the identification of new materials suitable for testing for the repair of craniofacial and orthopedic skeletal defects in humans. The present standard of care for such defects may be altered to eliminate bone grafts, decrease risks to patients, improve quality of life, and increase the armamentarium of the clinician.