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: 10240501
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10240501
• 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; biomaterial compatibility; bioprinting; bone; bone cell; 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