Novel coatings on titanium implants for the delivery of stem cells

描述(由申请人提供)：颅骨重建仍然是外科医生面临的挑战。虽然修复颅骨的黄金标准是自体骨，特别是从被移除的皮瓣中移植，但由于皮瓣感染或肿瘤组织渗入，通常需要替代物。使用移除的皮瓣的其他挑战包括年龄、保存困难、手术时机和解剖条件。因此，外科医生往往依赖钛网等异形材料，这些材料可以很容易地成形，具有类似骨的弹性系数，并且具有生物相容性。然而，钛网不能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，通过减少植入部位对内源性细胞迁移和增殖的需求来加速愈合。脂肪来源和骨髓来源的间充质干细胞(ASCs和BMSCs)在多种骨缺损和颅面重建模型中显示出支持骨生长的潜力。目前，ASCs和BMSCs是通过扩增培养或用抗体进行繁琐的阴性或阳性选择来纯化的。难以达到治疗数量的细胞以及分离过程中涉及的复杂处理步骤限制了干细胞在临床上的使用。为了解决这一未得到满足的需求，AffinEnergy使用噬菌体展示筛选来鉴定与干细胞高亲和力结合的多肽序列。在这一应用中，我们建议测试用这种多肽修饰钛表面以提高干细胞捕获和保留的可行性。这项技术将显著改善口腔和颅颌面钛植入物手术的结果。 与公共卫生相关：颅骨重建仍然是外科医生面临的挑战。一种建议的解决方案是使用成人干细胞来促进骨再生；然而，干细胞的使用受到组织中细胞频率较低的限制。在这一应用中，我们建议开发一种能够捕获和保留成人干细胞的钛植入物，以改善临床结果。

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.