Novel coatings on titanium implants for the delivery of stem cells

用于输送干细胞的钛植入物上的新型涂层

基本信息

批准号：
8392335
负责人：
Martyn Darby
金额：
$ 14.98万
依托单位：
AFFINERGY ,INC
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-15 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8392335
关键词：
Address Adipose tissue Affinity Age Animal Model Animals Antibodies Area Aspirate substance Autologous Binding Biocompatible Blood Platelets Blood Vessels Bone Growth Bone Marrow Bone Marrow Stem Cell Bone Regeneration Calvaria Cell Adhesion Cell Count Cell Proliferation Cell Separation Cells Clinic Clinical Containment Data Defect Elasticity Fiber Frequencies Goals Gold Growth Factor Harvest Healed Immune response Implant Link Measures Mesenchymal Stem Cells Modeling Modification Operative Surgical Procedures Oral Osseointegration Osteogenesis Outcome Peptides Phage Display Pharmaceutical Preparations Phase Phenotype Process Proliferating Rattus Safety Screening procedure Shapes Site Solutions Specificity Stem cells Surface Surgeon Surgical Flaps Technology Testing Therapeutic Time Tissues Titania Titanium Tumor Tissue adult stem cell biomaterial compatibility bone cell motility cell type craniofacial craniomaxillofacial cranium design healing implantation improved in vivo macrophage novel osteogenic prevent protein aminoacid sequence reconstruction restoration scaffold success

项目摘要

DESCRIPTION (provided by applicant): Calvarial reconstruction continues to present challenges for surgeons. Although the gold standard for restoration of the skull is autologous bone, particularly from the removed flap, substitutes are often necessary due to the flap becoming infected or infiltrated with tumor tissue. Other challenges to the use of the removed flap include age, difficulties with storage, surgery timing, and anatomical conditions. Therefore, the surgeon often relies on alloplastic materials such as titanium mesh, which can be easily shaped, has a modulus of elasticity similar to bone, and is biocompatible. However, titanium mesh does not provide the cells or growth factors needed to stimulate bone regeneration. One approach for bone regeneration is the combination of a scaffold with osteogenic cells to accelerate healing by reducing the need for endogenous cell migration and proliferation at the implant site. Adipose-derived and bone marrow-derived mesenchymal stem cells (ASCs and BMSCs, respectively) have shown potential to support bone growth in multiple models of bone defects and craniofacial reconstruction. Currently, ASCs and BMSCs are purified through culture expansion or through tedious negative or positive selections with antibodies. The difficulty achieving therapeutic numbers of cells and the complicated processing steps involved in their isolation have limited the use of stem cells in the clinic. To address this unmet need, Affinergy used phage display screening to identify peptide sequences that bind stem cells with high affinity. In this application, we propose to test the feasibility of modifying the surface of titanium with this peptide to improve the capture and retention of stem cells. The technology will significantly improve outcomes for oral and craniomaxillofacial surgeries with titanium implants. PUBLIC HEALTH RELEVANCE: Calvarial reconstruction continues to present challenges for surgeons. One proposed solution is the use of adult stem cells to augment bone regeneration; however, the use of stem cells has been limited by the low frequency of the cells in tissue. In this application, we propose to develop a titanium implant that can capture and retain adult stem cells to improve clinical outcomes.

描述（由申请人提供）：颅骨重建继续给外科医生带来挑战。虽然颅骨修复的金标准是自体骨，特别是来自切除的皮瓣，但由于皮瓣被肿瘤组织感染或浸润，通常需要替代品。使用移除的皮瓣的其他挑战包括年龄、储存困难、手术时机和解剖条件。因此，外科医生经常依赖钛网等同种异体材料，这种材料易于成型，具有与骨骼相似的弹性模量，并且具有生物相容性。然而，钛网不提供刺激骨再生所需的细胞或生长因子。骨再生的一种方法是将支架与成骨细胞相结合，通过减少植入部位内源细胞迁移和增殖的需要来加速愈合。脂肪来源和骨髓来源的间充质干细胞（分别为 ASC 和 BMSC）已显示出在多种骨缺损和颅面重建模型中支持骨生长的潜力。目前，ASC 和 BMSC 是通过培养扩增或通过繁琐的抗体阴性或阳性选择来纯化的。获得治疗数量的细胞的困难以及分离细胞所涉及的复杂的处理步骤限制了干细胞在临床中的使用。为了解决这一未满足的需求，Affinergy 使用噬菌体展示筛选来鉴定以高亲和力结合干细胞的肽序列。在此应用中，我们建议测试用这种肽修饰钛表面以改善干细胞捕获和保留的可行性。该技术将显着改善钛种植体口腔和颅颌面手术的效果。公共卫生相关性：颅骨重建继续给外科医生带来挑战。一种提议的解决方案是使用成体干细胞来增强骨再生。然而，干细胞的使用受到组织中细胞频率低的限制。在此应用中，我们建议开发一种钛植入物，可以捕获并保留成体干细胞，以改善临床结果。