In Situ Hardening Cellular Constructs for Craniofacial Bone Regeneration

项目总结/摘要 拟议的项目旨在开发可注射的原位硬化细胞聚合物结构，用于修复 颅面骨缺损除了开发非常适合这种应用的生物材料外，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， 从所描述的研究中阐明的知识可以广泛地应用于组织的其他领域 工程.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 其在体温下经历物理凝胶化和化学交联。这些水凝胶还将 含有钙结合域，假设其在注射后硬化材料并诱导 包被的骨髓基质细胞在基质矿化后的骨分化。多种方法 为了评估水凝胶的物理化学特性，将使用体外和体内试验 以评价水凝胶的细胞相容性、稳定性和降解。第二 具体目的涉及研究不同水凝胶制剂的效果和所得的物理性质， 参数对包封细胞活力和骨再生的影响在公认的临界范围内， 大小大鼠颅骨缺损模型。最后，第三个具体目标是研究不同细胞的影响， 参数如初始接种密度和包封骨髓的骨分化阶段 基质细胞对水凝胶构建体的骨再生潜力有影响。体内研究 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， 适用于临床应用，关于骨再生和结构生物相容性的功效是 在研究的每个阶段进行评估。项目叙述 颅面骨异常，通常由出生缺陷、癌症或创伤性损伤引起， 世界各地的人们，并已被证明大大降低了病人和那些 身边目前，用于纠正这种异常的唯一治疗选择涉及侵入性的，并且通常 使用组织移植或某种形式的可植入生物材料的重复手术努力，其中许多 并不适合这种应用。本提案中所述的项目旨在开发新的复合材料 生物材料1）是可注射的，从而消除或减少对侵入性手术的需要，和2）促进 骨再生，从而消除了对组织移植的需要，并且天然骨在 缺损

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.