In Situ Hardening Cellular Constructs for Craniofacial Bone Regeneration

用于颅面骨再生的原位硬化细胞结构

• 批准号: 8217161
• 负责人: ANTONIOS G. MIKOS
• 金额: $ 32.31万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-10 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8217161
• 关键词: Area; Biocompatible Materials; Body Temperature; Bone Regeneration; Bone Tissue; Calcium; Calcium Binding; Calcium-Binding Domain; Calvaria; Cell Differentiation process; Cell Survival; Cells; Cephalic; Characteristics; Chemicals; Congenital Abnormality; Defect; Drug Formulations; Encapsulated; Gel; Goals; Hydrogels; In Situ; In Vitro; Injectable; Injection of therapeutic agent; Injury; Investigation; Kinetics; Knowledge; Lead; Malignant Neoplasms; Marrow; Mechanics; Methods; Modeling; Natural regeneration; Operative Surgical Procedures; Osteogenesis; Patients; Polymers; Porosity; Property; Quality of life; Rattus; Site; Staging; Stromal Cells; Swelling; Testing; Tissue Engineering; Tissue Grafts; abstracting; biomaterial compatibility; bone; clinical application; craniofacial; craniofacial repair; crosslink; density; experience; functional group; in vivo; mineralization; novel; osteoblast differentiation; regenerative; tissue repair

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.

项目摘要/摘要 拟议的项目旨在开发可注射的原位硬化细胞聚合物构建体以修复 颅面骨缺损。除了开发适合本应用程序的生物材料外，该项目还将 还研究对许多关键材料和细胞参数的骨再生的影响， 从所描述的研究中阐明的知识可以广泛应用于其他组织 工程。该项目的第一个具体目的是合成和表征新型可注射水凝胶 在体温下进行物理凝胶和化学交联。这些水凝胶也将 包含钙结合域，这些结合域假设可以在注射后硬化材料并诱导材料 基质矿化后，封装的骨髓基质细胞的骨化分化。多种方法 为了评估水凝胶的理化特征，将在体外和体内测试中使用 将进行评估水凝胶的细胞相容性，稳定性和降解。第二个 具体目的涉及对不同水凝胶配方的作用和结果的研究 参数具有封装的细胞活力和骨骼再生的良好临界 尺寸大鼠钙钙缺损模型。最后，第三个特定目的是研究改变细胞的影响 参数，例如初始播种密度和封装骨髓的骨化阶段 基质细胞具有水凝胶构建体的骨再生潜力。体内研究是 纳入项目的每个目标，使得与开发材料的长期目标保持一致 适合临床应用，关于骨骼再生和构造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，通常是由于先天缺陷，癌症或创伤性损伤引起的，折磨了许多 全球人，已被证明会大大降低患者的生活质量和那些人的生活质量 在他们周围。目前，纠正这种异常的唯一治疗方法涉及侵入性，并且通常 使用组织嫁接或某种形式的可植入生物材料的重复手术努力，其中许多 对于此应用而言并不理想。该提案中描述的项目旨在开发新的综合 1）可注射的生物材料，从而消除或减少对侵入性手术的需求，2）促进 骨骼再生，使组织嫁接的需求被消除，自然骨被再生 缺点。

项目成果

Characterization of an injectable, degradable polymer for mechanical stabilization of mandibular fractures.

• DOI: 10.1002/jbm.b.33216
• 发表时间: 2015-04
• 期刊: Journal of biomedical materials research. Part B, Applied biomaterials
• 作者: Allan M. Henslee;Diana M. Yoon;B. Lu;Joseph Yu;Andrew A Arango;Liann P Marruffo;L. Seng;T. D. Anver;H. Ather;M. Nair;Sean O Piper;N. Demian;M. Wong;F. Kasper;A. Mikos

Effects of cellular parameters on the in vitro osteogenic potential of dual-gelling mesenchymal stem cell-laden hydrogels.

• DOI: 10.1080/09205063.2016.1195157
• 发表时间: 2016-08
• 期刊: Journal of biomaterials science. Polymer edition
• 作者: Vo TN;Tabata Y;Mikos AG
• 通讯作者: Mikos AG

Biodegradable composite scaffolds incorporating an intramedullary rod and delivering bone morphogenetic protein-2 for stabilization and bone regeneration in segmental long bone defects.

• DOI: 10.1016/j.actbio.2011.06.043
• 发表时间: 2011-10
• 期刊: ACTA BIOMATERIALIA
• 影响因子: 9.7
• 作者: Henslee, A. M.;Spicer, P. P.;Yoon, D. M.;Nair, M. B.;Meretoja, V. V.;Witherel, K. E.;Jansen, J. A.;Mikos, A. G.;Kasper, F. K.
• 通讯作者: Kasper, F. K.

Structure-property evaluation of thermally and chemically gelling injectable hydrogels for tissue engineering.

• DOI: 10.1021/bm300797m
• 发表时间: 2012-09-10
• 期刊: BIOMACROMOLECULES
• 影响因子: 6.2
• 作者: Ekenseair, Adam K.;Boere, Kristel W. M.;Tzouanas, Stephanie N.;Vo, Tiffany N.;Kasper, F. Kurtis;Mikos, Antonios G.
• 通讯作者: Mikos, Antonios G.

Synthesis, physicochemical characterization, and cytocompatibility of bioresorbable, dual-gelling injectable hydrogels.

• DOI: 10.1021/bm401413c
• 发表时间: 2014-01-13
• 期刊: BIOMACROMOLECULES
• 影响因子: 6.2
• 作者: Vo, Tiffany N.;Ekenseair, Adam K.;Kasper, F. Kurtis;Mikos, Antonios G.
• 通讯作者: Mikos, Antonios G.