Department of Orthopaedic Surgery, University of California, Davis, 4860 Y Street, Suite 3800, Sacramento, CA 95817, USA.
Department of Orthopaedic Surgery, University of California, Davis, 4860 Y Street, Suite 3800, Sacramento, CA 95817, USA.
Acta Biomater. 2014 Dec;10(12):5099-5105. doi: 10.1016/j.actbio.2014.08.019. Epub 2014 Aug 24.
Specific and targeted delivery of medical therapies continues to be a challenge for the optimal treatment of multiple medical conditions. Technological advances permit physicians to target most sites of the body. However, after the intervention, physicians rely on systemic medications that need frequent dosing and may have noxious side effects. A novel system combining the temporal flexibility of systemic drug delivery and the spatial control of injectable biomaterials would improve the spatiotemporal control of medical therapies. Here we present an implantable biomaterial that harnesses in vivo click chemistry to enhance the delivery of suitable small molecules by an order of magnitude. The results demonstrate a simple and modular method to modify a biomaterial with small molecules in vitro and present an example of a polysaccharide modified hours after in vivo implantation. This approach provides the ability to precisely control the moment when biochemical and/or physical signals may appear in an implanted biomaterial. This is the first step towards the construction of a biomaterial that enhances the spatial location of systemic small molecules via in vivo chemical delivery.
特定和靶向的医疗疗法的传递对于多种医疗条件的最佳治疗仍然是一个挑战。技术进步使医生能够针对身体的大多数部位。然而,在干预之后,医生依赖需要频繁给药且可能具有有害副作用的全身药物。一种将全身药物输送的时间灵活性与可注射生物材料的空间控制相结合的新系统将改善医疗疗法的时空控制。在这里,我们提出了一种可植入生物材料,利用体内点击化学将合适的小分子的输送增强一个数量级。结果表明了一种简单且模块化的方法,用于在体外用小分子修饰生物材料,并提供了体内植入数小时后多糖修饰的实例。这种方法提供了精确控制何时在植入的生物材料中出现生化和/或物理信号的能力。这是朝着构建通过体内化学输送增强全身小分子空间定位的生物材料迈出的第一步。