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.

项目总结 本研究的长期目标是开发一种基于纤维素的半刚性生物活性支架。 纳米金刚石(CeND)多孔纤维用于颅面骨组织再生。生物活性支架将是 使用电纺技术以纤维的形式制备的。CeND随着生长和生长而修改 黏附因子旨在提高骨组织再生率。我们将实现这一总体目标。 通过追求三个主要的具体目标进行研究：1)配制生物活性CeND溶液以产生多孔 2)利用生物反应器评价生物活性CeND支架的体外生物相容性。 建立三维组织模型；3)测定生物活性CeND支架在颅骨中的成骨能力 大鼠的缺陷。我们假设，通过将骨诱导生长因子(即BMP-2)与 在CeND纤维支架中的黏附因子(即KSRS和RGD肽)，我们将能够增强 新形成的矿化组织沿支架的沉积速率。一旦生物活性支架 我们将对有无生长的纤维进行物理、机械和生物特性的表征 和粘附性因素。生物学特性将在体外利用人间充质细胞进行。 干细胞(MSCs)。具体地说，我们将使用免疫组织化学技术来确定 细胞在与生物活性柔性支架接触时生长、成熟、黏附和分化。在- 体外实验将在慢转侧血管(STLV)生物反应器中进行，以生成3D 脚手架上的组织模型。我们预计这种体外技术将使我们能够更好地预测 支架在体内的性能。我们将能够回答有关细胞表面的基本问题 相互作用的目标是提出一种具有增强的仿生性能的柔性生物活性支架。这 这项工作将揭示半刚性支架在颅面骨组织再生和修复中的应用 对于处理诸如腭裂和其他颅颌面部等医疗疾病是至关重要的 条件。