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.

项目概要/摘要 拟议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。除了开发非常适合该应用的生物材料外，该项目还将 还研究了许多关键材料和细胞参数对骨再生的影响，例如 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。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 在体温下发生物理凝胶化和化学交联。这些水凝胶还将 含有钙结合结构域，推测这些结构域可以在注射后使材料硬化并诱导 基质矿化后封装的骨髓基质细胞的骨分化。多种方法 评估将使用的水凝胶的物理化学特性，并进行体外和体内测试 将进行评估水凝胶的细胞相容性、稳定性和降解。第二个 具体目标包括研究不同水凝胶配方的效果以及由此产生的物理效果 参数对封装细胞活力和骨再生都有影响，在既定的临界范围内 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，例如初始接种密度和封装骨髓的骨分化阶段 基质细胞具有水凝胶结构的骨再生潜力。体内研究是 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 适合临床应用，骨再生和构建生物相容性方面的功效 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、癌症或外伤引起，困扰着许多人 世界各地的人们，并已被证明大大降低了患者和其他人的生活质量 他们周围。目前，纠正此类异常的唯一治疗选择涉及侵入性且通常 使用组织移植或某种形式的可植入生物材料反复进行手术，其中许多 对于这个应用来说并不理想。本提案中描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，2) 促进 骨再生，从而消除了组织移植的需要，并在一定时间内再生天然骨 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.