Self-Assembled Biomimetic Scaffolds

描述(申请人提供)：目前的合成支架材料无法引导成骨细胞增殖、分化为成骨细胞，并产生足够数量的骨组织，限制了合成支架在骨科、牙科和颅面外科等关键领域的骨移植应用的发展。我们的长期目标是创造合理设计的、受生物启发的组织工程结构，促进骨形成和增强骨修复。作为实现这一目标的第一步，这一应用的目标是设计具有可控结构和改善力学性能的新型支架，通过利用棒-线圈嵌段共聚物的相分离和自组装特性来呈现仿生配体。中心假说是，通过在超分子水平上集成“活性”聚合和自组装来精确控制聚合物嵌段的设计和结构，将导致具有增强的机械和结构性能和功能的支架。在目标1中，将利用棒-线圈嵌段共聚物在介观尺度上的自组装特性与共价交联策略相结合，以设计具有可控结构和力学性能的支架。在目标2中，将制备以聚乳酸为基础的功能化共聚物，这种聚合物可以接枝耐蛋白质的聚乙二醇涂层，并通过悬挂锚定单元固定纤维连接蛋白模拟配体。成骨细胞的黏附、增殖和分化将在功能化和非功能化的聚合物和支架上以及当前生物医学聚合物的薄膜上进行评估。这项研究有望取得以下成果：a)建立聚降冰片烯/聚乳酸嵌段共聚物作为仿生支架的合成、表征、自组装和发泡的基本设计原则；b)验证所提出的利用光引发共价交联增强三维泡沫结构的策略；c)建立具有生物活性部分的聚乳酸S功能化的模块化方法。总的来说，这些研究将验证所提出的高强度仿生支架的新概念。

DESCRIPTION (provided by applicant): The inability of current synthetic scaffold materials to direct osteogenic cells to proliferate, differentiate into osteoblasts, and produce sufficient quantities of bone tissue limits the development of synthetic scaffolds for bone grafting applications in crucial areas such as orthopedic, dental, and craniofacial procedures. Our long-term goal is to create rationally designed, bio-inspired tissue-engineered constructs that promote bone formation and enhanced bone repair. As a first step toward this goal, the objective of this application is to engineer novel scaffolds with controlled architectures and improved mechanical properties that present biomimetic ligands by exploiting phase separation and self-assembly properties of rod-coil block copolymers. The central hypothesis is that precise control of polymer block design and structure through integration of "living" polymerization and self-assembly at the supramolecular levels will lead to scaffolds with enhanced mechanical and structural properties and functionality. In Aim 1, self-assembly properties at the meso-scale of rod-coil block copolymers in combination with covalent cross-linking strategies will be exploited in order to engineer scaffolds with controlled structural and mechanical properties. In Aim 2, functionalized copolymers based on poly(lactic acid) will be prepared which allow for grafting of protein-resistant poly(ethylene glycol) coatings and the immobilization of fibronectin-mimetic ligands through pendant anchoring units. Osteoblast adhesion, proliferation, and differentiation will be evaluated on functionalized and non-functionalized polymers and scaffolds as well as films of current biomedical polymers. This research is expected to yield the following outcomes: a) establishment of basic design principles for the synthesis, characterization, self-assembly, and foaming of poly(norbornene)/poly(lactic acid) block copolymers as biomimetic scaffolds, b) verification of the proposed strategy of using photoinitiated covalent cross-linking to reinforce three-dimensional foamed structures and c) establishment of a modular approach towards the functionalization of poly(lactic acid)s with biological active moieties. Collectively, these studies will validate the proposed novel concepts towards high strength biomimetic scaffolds.