Bioactive cellulose-nanodiamond (CeND) scaffolds for applications in craniofacial bone tissue regeneration

生物活性纤维素-纳米金刚石 (CeND) 支架在颅面骨组织再生中的应用

• 批准号: 10467026
• 负责人: Eduardo Nicolau
• 金额: $ 37.25万
• 依托单位: UNIVERSITY OF PUERTO RICO RIO PIEDRAS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10467026
• 关键词: 3-Dimensional; Adhesions; Allogenic; Area; Autologous; Biocompatible Materials; Biological; Biomimetic Materials; Biomimetics; Bioreactors; Bone Morphogenetic Proteins; Bone Regeneration; Bone Tissue; Bone Transplantation; Cartilage; Cell Membrane Proteins; Cell surface; Cells; Cellulose; Cephalic; Characteristics; Charge; Cleft Palate; Clinical; Craniofacial Abnormalities; Cytoskeleton; Defect; Dental; Deposition; Development; Drug Delivery Systems; Elements; Environment; Extracellular Matrix; Fiber; Fibrinogen; Goals; Growth; Growth Factor; Health; Human; Immune; Implant; In Vitro; Institutes; Integrins; Knowledge; Laboratories; Lateral; Ligands; Light; Mechanics; Medical; Mesenchymal Stem Cells; Minerals; Modeling; Morbidity - disease rate; Natural regeneration; Osteoblasts; Peptides; Performance; Perfusion; Polymers; Population; Porosity; Process; Property; Proteins; Proteoglycan; RGD (sequence); Rattus; Research; Site; Structure; Techniques; Testing; Therapeutic; Time; Tissue Engineering; Tissue Model; Tissues; United States National Institutes of Health; Work; allogenic bone transplantation; analog; base; bioactive scaffold; biomaterial compatibility; bioprinting; bone; bone cell; bone scaffold; clinical application; cost; craniofacial; craniofacial bone; craniomaxillofacial; design; experimental study; flexibility; improved; in vivo; interest; nanodiamond; novel therapeutics; reconstruction; scaffold; stem cells; tissue regeneration; tissue repair

PROJECT SUMMARY The long-term goal of this research is to develop a semi-rigid bioactive scaffold based on cellulose- nanodiamond (CeND) porous fibers for craniofacial bone tissue regeneration. The bioactive scaffolds will be prepared in the form of fibers using the electrospining technique. The CeND are modified with growth and adhesion factors aiming to improve the rate of bone tissue regeneration. We will achieve the overall goal of this research by pursuing three main specific aims: 1) To formulate bioactive CeND solutions to generate porous scaffolds; 2) To evaluate the biocompatibility of the bioactive CeND scaffolds in vitro using a bioreactor to generate 3D tissue models; 3) To determine the osteoinductive capacity of bioactive CeND scaffolds in cranial defects in rats. We hypothesize that by incorporating osteoinductive growth factors (i.e. BMP-2) along with adhesion factors (i.e. KSRS and RGD peptides) in CeND-fibered scaffolds, we will be able to enhance the deposition rate of newly formed mineralized tissue along the scaffold. Once the bioactive scaffolds are fabricated we will physically, mechanically and biologically characterize the fibers with and without the growth and adhesion factors. The biological characterization will be performed in-vitro utilizing human mesenchymal stem cells (MSCs). Specifically, we will use inmmunohistochemical techniques to determine the ability of the cells to growth, mature, adhere and differentiate when in contact with the bioactive flexible scaffolds. The in- vitro experiments will be performed in Slow-Turning Lateral Vessel (STLV) bioreactor in order to generate 3D tissue models over the scaffolds. We expect that this in-vitro technique will allow us to better predict the performance of the scaffolds in-vivo. We will be able to answer fundamental questions regarding cell-surface interactions with the goal of proposing a flexible bioactive scaffold with enhanced biomimetic properties. This work will shed light on the use of semi-rigid scaffolds for craniofacial bone tissue regeneration and repair that is of utmost importance to tackle medical conditions such as the cleft palate and other craniomaxillofacial conditions.

项目摘要 这项研究的长期目标是开发基于纤维素 - 纳米木德（Cend）多孔纤维用于颅面骨组织再生。生物活性脚手架将是 使用电热技术以纤维的形式制备。将随着增长和 旨在提高骨组织再生速率的粘附因子。我们将实现这一总体目标 通过追求三个主要特定目标来进行研究：1）制定生物活性的Cend解决方案以产生多孔 脚手架； 2）使用生物反应器在体外评估生物活性造成支架的生物相容性 生成3D组织模型； 3）确定颅中生物活性造成支架的骨能力 大鼠缺陷。我们假设通过纳入骨诱导生长因子（即BMP-2）以及 粘附因子（即KSRS和RGD肽）在Cend纤维支架中，我们将能够增强 沿支架的新形成的矿化组织的沉积速率。一旦生物活性脚手架 制造的我们将在物理，机械和生物学上以有或没有生长的形式来表征纤维 和粘附因子。利用人间充质的生物学表征将在体外进行 干细胞（MSC）。具体而言，我们将使用Inmmuno组织化学技术来确定 与生物活性柔性支架接触时，细胞会生长，成熟，粘附和分化。内 体外实验将在缓慢转变的侧容器（STLV）生物反应器中进行，以生成3D 脚手架上的组织模型。我们希望这种体外技术将使我们能够更好地预测 脚手架的性能。我们将能够回答有关细胞表面的基本问题 相互作用的目的是提出具有增强仿生特性的柔性生物活性支架。这 工作将阐明使用半刚性支架用于颅骨组织再生和修复 要解决诸如left裂和其他颅颌面等医学状况的最重要意义 状况。