3-D BIOMIMETIC SCAFFOLDS FOR BONE TISSUE ENGINEERING

描述（改编自研究者摘要）： 骨骼缺陷是一个主要的临床挑战， 每年进行的外科手术。骨再生新策略 由于现有技术的局限性，一个新的策略是 为了产生其中将自体细胞接种到多孔， 可降解支架支架在结构上支撑细胞， 在生物学上，允许它们生长并分泌新的细胞外基质。 最佳的组织生长与支架降解同时发生。程度 然而，新骨形成的时间依赖于材料并且不可预测。我们 因此，寻求建立材料化学参数， 骨细胞功能为了实现这一目标，我们开发了：（1）体外 扩增人骨髓基质细胞（BMSC）的培养方法; (2)聚合物加工技术，可重复制造高度多孔的3D 聚（乳酸-乙醇酸共聚物）支架，已成功地用于 包括骨在内的多种组织的工程化;（3）材料科学设计 这些策略使我们能够通过生物仿生学来改变 支架和支架表面的微环境;和（4）关键的 在免疫功能低下小鼠中建立的颅骨缺损模型， 人BMSC能够在动物模型中形成新骨。全球 这项研究的假设是，细胞外微环境 调节人BMSC分化的能力 朝向成骨细胞表型，因此控制生物矿化， 再生骨的结构完整性。结果从我们和其他 实验室支持这一假设，通过合成一系列 模拟仿生材料的模型。首先，我们合成了对环境敏感的 或“智能”支架， 降解其次，我们合成了一种表面 自我矿化成生物磷灰石第三，我们使用功能分级 支架，其中矿化是空间控制的。的理由 这三种仿生策略中的每一种都是大自然设计的， 骷髅骨骼系统能够使用最少的 因为生物学利用了设计方法，其中包括 适应环境线索的能力（即“聪明”），一个层次 一个由优雅的矿物合成组成的组织， 通过在组成上具有梯度而优化生理功能， 结构在拟议的研究中，我们的目标是利用每一个方面， 3仿生策略，努力创造生物材料，将调节 生物反应以可控的方式进行。

DESCRIPTION (Adapted from the Investigator's Abstract): Reconstruction of skeletal defects represents a major clinical challenge with over 1 million surgical procedures performed each year. New strategies of regenerating bone are needed because of limitations with existing techniques. One new strategy is to create a composite graft in which autologous cells are seeded onto a porous, degradable scaffold. The scaffold supports the cells, structurally and biologically, allowing them to grow and secrete new extracellular matrix. Optimally tissue growth occurs concurrent with scaffold degradation. The degree of new bone formation is, however, material dependent and not predictable. We therefore seek to establish material chemistry parameters that could optimize bone cell function. In pursuit of this goal, we have developed: (1) in vitro culture methods in which human bone marrow stromal cells (BMSCs) are expanded; (2) polymer processing techniques to reproducibly fabricate highly porous 3D poly(lactic-co-glycolic) scaffolds, which have been successfully used to engineer a number of tissues including bone; (3) materials science design strategies which enable us to biomimetically modify both the internal microenvironment of a scaffold and the scaffold surface; and (4) a critical size cranial defect model in an immunocompromised mouse which has shown that the human BMSCs are capable of forming new bone in an animal model. The global hypothesis of the proposed research is that the extracellular microenvironment provided by the scaffold modulates the ability of human BMSCs to differentiate toward an osteoblast phenotype, and therefore controls biomineralization and structural integrity of regenerated bone. Results from our and other laboratories support this hypothesis, which is tested by synthesizing a series of model biomimetic materials. First, we synthesize environmentally responsive or "smart" scaffolds that buffer the microenvironment upon scaffold degradation. Second, we synthesize scaffolds with a surface that self-mineralizes into a biological apatite. Third, we use functionally-graded scaffolds in which mineralization is spatially controlled. The rationale for each of these 3 biomimetic strategies lies in the way nature has designed the skeleton. The skeletal system is able to perform its functions using a minimum amount of mass because biology has utilized design approaches, which include the ability to adapt to environmental cues (i.e. "smartness"), a hierarchical organization consisting of elegant mineral synthesis, and an organization that is optimized for physiological function by having gradients in composition and structure. In the proposed studies, we aim to exploit aspects of each of these 3 biomimetic strategies in an effort to create biomaterials that will modulate biological response in a controlled manner.