In Situ Hardening Cellular Constructs for Craniofacial Bone Regeneration

项目摘要/摘要 拟议的项目旨在开发可注射的、原位硬化的细胞-聚合物结构，用于修复 颅面骨缺损症。除了开发适合这一应用的生物材料外，该项目还将 还研究了一些关键材料和细胞参数对骨再生的影响，如 从所描述的研究中阐明的知识可以广泛应用于组织的其他领域 工程学。该项目的第一个具体目标是合成和表征新型可注射水凝胶。 在体温下经历物理凝胶化和化学交联化。这些水凝胶还将 含有钙结合结构域，假设既能在注射后使材料硬化，又能诱导 基质矿化后包裹的骨髓基质细胞的成骨分化。各种方法 为了评估水凝胶的物理化学特性，将使用体外和体内测试 将进行细胞相容性、稳定性和水凝胶降解性的评估。第二 具体目标包括研究不同水凝胶配方的效果和所产生的物理 参数对包被的细胞活性和骨再生都有影响 大鼠颅骨缺损模型。最后，第三个具体目标是研究变化的细胞 包埋骨髓的初始种植密度和成骨分化阶段等参数 基质细胞具有水凝胶构建物的骨再生潜力。活体研究是 纳入项目的每个目标，以便与开发材料的长期目标保持一致 适合于临床应用，在骨再生和构建生物相容性方面的有效性是 在研究的每个阶段进行评估。项目叙事 颅面部骨骼异常，通常是由出生缺陷、癌症或创伤引起的，困扰着许多人。 已经被证明会极大地降低患者和患者的生活质量。 在他们周围。目前，纠正这种异常的唯一治疗选择是侵入性的，而且通常 使用组织移植或某种形式的植入性生物材料进行重复手术，其中许多 对于此应用程序来说并不理想。本提案中所述的项目旨在开发新的复合材料 生物材料，1)可注射，从而消除或减少侵入性手术的需要，以及2)促进 骨再生，从而消除了对组织移植的需要，并在一年内再生了天然骨 叛逃。

Project Summary/Abstract The proposed project aims to develop injectable, in situ hardening cell-polymer constructs for the repair of craniofacial bone defects. In addition to developing biomaterials well suited to this application, the project will also investigate the effect on bone regeneration of a number of critical material and cellular parameters, such that knowledge elucidated from the described studies can be broadly applied to other areas of tissue engineering. The first specific aim of the project is to synthesize and characterize novel injectable hydrogels that undergo physical gelation and chemical crosslinking at body temperature. These hydrogels will also contain calcium-binding domains that are hypothesized to both harden the material after injection and induce osteodifferentiation of encapsulated marrow stromal cells following matrix mineralization. A variety of methods to assess the physicochemical characteristics of the hydrogels will be used, and both in vitro and in vivo testing will be performed to evaluate cytocompatibility, stability, and degradation of the hydrogels. The second specific aim involves investigations of the effect different hydrogel formulations and the resultant physical parameters have on both encapsulated cell viability and bone regeneration within the well-established critical size rat calvarial defect model. Finally, the third specific aim is to investigate the effects that varying cellular parameters such as initial seeding density and the stage of osteodifferentiation of encapsulated marrow stromal cells have on the bone regenerative potential of the hydrogel constructs. In vivo studies are incorporated into each aim of the project such that, in keeping with the long-term goal of developing materials appropriate for clinical applications, efficacy with respect to bone regeneration and construct biocompatibility is assessed at each stage of the study. Project Narrative Craniofacial bone abnormalities, typically resulting from birth defects, cancer, or traumatic injuries, afflict many people worldwide and have been shown to greatly diminish the quality of life of both the patient and those around them. Currently, the only treatment options for correcting such abnormalities involve invasive and often repeated surgical efforts using either tissue grafting or some form of implantable biomaterial, many of which are not ideal for this application. The project described in this proposal aims to develop new composite biomaterials that 1) are injectable, thus eliminating or reducing the need for invasive surgery, and 2) promote bone regeneration, such that the need for tissue grafting is eliminated and natural bone is regenerated within a defect.