Integrative colloidal gels for cranial defect repair

用于颅骨缺损修复的一体化胶体凝胶

• 批准号: 8239401
• 负责人: Cory Berkland
• 金额: $ 35.92万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8239401
• 关键词: Anabolism; Animals; Artificial nanoparticles; Biochemistry; Biocompatible Materials; Bone Cements; Bone Marrow; Bone Regeneration; Bone Tissue; Calvaria; Categories; Cephalic; Ceramics; Charge; Chemistry; Chondroitin Sulfates; Clinic; Clinical; Clinical Research; Colloids; Data; Defect; Electrostatics; Engineering; Environment; Filler; Foundations; Future; Gel; Glycosaminoglycans; Goals; Growth Factor; Hydrogels; Hydroxyapatites; In Vitro; Institutes; Lead; Liquid substance; Liver Regeneration; Medical; Mesenchymal Stem Cells; Metals; Mission; Modeling; Molds; Musculoskeletal; Natural regeneration; Necrosis; Operative Surgical Procedures; Osteogenesis; Paste substance; Pharmaceutical Preparations; Polymers; Polymethyl Methacrylate; Property; Publishing; Qualifying; Rattus; Relative (related person); Research; Research Personnel; Rheology; Signal Transduction; Site; Solid; Stress; Surface; Surgeon; Technology; Testing; Tissue Engineering; Tissues; Vascular Endothelial Growth Factors; Weight-Bearing state; base; bone; bone morphogenetic protein 2; cohesion; commercialization; controlled release; craniofacial; design; in vivo; innovation; nanoparticle; novel; osteochondral tissue; osteogenic; polysulfated glycosaminoglycan; prototype; reconstruction; repaired; scaffold; stem cell differentiation; three dimensional structure; tissue regeneration

DESCRIPTION (provided by applicant): The long-term objective of this application is to deliver a unique biomaterial that can easily be molded into place by a surgeon, and will resorb as it induces rapid tissue regeneration. Toward this objective, we invented a biomaterial based on colloidal gel technology, which we have demonstrated to be effective in calvarial defect regeneration. The key feature that distinguishes colloidal gels from the two major classes of scaffolding biomaterials (hydrogels and solid scaffolds) is their paste-like rheology, which in turn is attributed to electrostatic interaction of the nanoparticle constituents. Although this new class of scaffolds is highly versatile in its unbounded combination of possible synthetic and natural nanoparticles, we have elected to focus on a combination of naturally occurring materials with controlled release of bioactive signals. Therefore, the objective of this project is to develop a malleable material that can be spread into place in a cranial defect, while releasing bioactive factors and allowing native bone to penetrate and resorb the material. The corresponding central hypothesis is that the growth factor-loaded colloidal gels will regenerate bone in cranial defects significantly faster and more completely than unloaded colloidal gels or commercial hydroxyapatite bone fillers. To test this hypothesis, we propose three specific aims: 1) to synthesize and characterize novel colloidal gels with modulated rheological properties, 2) to engineer and refine colloidal gels in vitro, and 3) to determine the efficacy of colloidal gels in a rat cranial defect model. Building on our published characterization of prototype colloidal gels, our overall strategy will be to significantly expand our repertoire first by evaluating the rheological and release properties of a variety of combinations of specific sulfated glycosaminoglycans (GAGs, negatively charged) and hydroxyapatite nanoparticles (positively charged), which have been identified as an internally cohesive colloidal gel network. A specific subset of these combinations will then be thoroughly evaluated in vitro for their efficacy in promoting osteogenesis with rat bone marrow-derived mesenchymal stem cells (BMSCs). The most promising groups from these in vitro studies will be evaluated in critical-sized rat calvarial defects, with the project thereby culminating in the identification of the leading combination of GAGs, hydroxyapatite, and osteogenic and angiogenic signals for calvarial defect regeneration. Successful completion of this project will lay the foundation for an entirely new sub-field for tissue engineering scaffolding biomaterials. The true impact of this line of research is its extraordinary versatility and relatively straightforward set of design principles as a means to create bioresorbable, pastes of tunable consistency, with the capability for controlled release of bioactive signals. We and other investigators world- wide will be able to explore a seemingly infinite number of innovative combinations of interactive nanoparticles for applications beyond calvarial defect regeneration, from osteochondral regeneration to liver regeneration to any other conceivable application where such a material is desired. PUBLIC HEALTH RELEVANCE: Reconstruction of craniofacial bone currently relies on materials that require surgical placement and that do not adequately facilitate regeneration of native bone. There is an urgent need to identify new materials that enable reconstruction of bone in general and the proposed research will investigate a unique pseudoplastic biomaterial for conducting rapid bone regeneration.

描述（由申请人提供）：本申请的长期目标是提供独特的生物材料，可以轻松地由外科医生模制成适当的生物材料，并会在诱导快速组织再生时吸收。朝向这一目标，我们发明了基于胶体凝胶技术的生物材料，我们证明该材料在钙典写的缺陷再生中有效。将胶体凝胶与两个主要类脚手材料（水凝胶和实心支架）类别的主要特征是它们的糊状流变学，这又归因于纳米粒子成分的静电相互作用。尽管这类新的脚手架在可能的合成和天然纳米颗粒的无界组合中具有高度的用途，但我们选择着重于自然存在的材料与受控释放生物活性信号的组合。因此，该项目的目的是开发可延展的材料，该材料可以在颅骨缺陷中扩散到位，同时释放生物活性因子并允许天然骨骼穿透并吸收材料。相应的中心假设是，与未载的胶体凝胶或商业羟基磷灰石骨填充剂相比，颅缺损中的生长因子胶体凝胶将在颅缺损中再生骨骼的再生。为了检验这一假设，我们提出了三个特定的目的：1）综合和表征具有调制性的胶体凝胶的新型胶体凝胶，2）在体外工程和改进胶体凝胶，以及3）以确定胶体凝胶在大鼠颅缺陷模型中的有效性。 Building on our published characterization of prototype colloidal gels, our overall strategy will be to significantly expand our repertoire first by evaluating the rheological and release properties of a variety of combinations of specific sulfated glycosaminoglycans (GAGs, negatively charged) and hydroxyapatite nanoparticles (positively charged), which have been identified as an internally cohesive colloidal gel network.然后，将在体外彻底评估这些组合的特定子集，以用大鼠骨骨髓来源的间充质干细胞（BMSC）促进成骨的功效。这些体外研究中最有希望的群体将在关键尺寸的大鼠颅缺陷中进行评估，因此该项目在鉴定GAG，羟基磷灰石以及肠op骨和血管生成信号的主要组合方面达到了最终形式。 该项目的成功完成将为组织工程脚手材料的全新子场奠定基础。这一研究的真正影响是其非凡的多功能性和相对简单的设计原理集，作为创建可调式一致性的可生物令人难命的糊状物的一种手段，并具有控制生物活性信号的控制能力。我们和其他研究人员（全球范围内）将能够探索互动纳米颗粒的数量无限数量的创新组合，用于从骨软骨再生到肝脏再生到肝脏再生再到任何其他可能的应用应用，在需要这种材料的情况下，都可以使用钙质缺陷再生。 公共卫生相关性：重建颅面骨骼目前依赖需要手术放置并且无法充分促进天然骨骼再生的材料。迫切需要确定一般能够重建骨骼的新材料，拟议的研究将研究一种独特的假性生物材料，用于进行快速骨再生。