Department of Radiology, Michigan State University, East Lansing, MI 48824, USA; Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI 48824, USA.
Department of Radiology, Michigan State University, East Lansing, MI 48824, USA; Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI 48824, USA.
Acta Biomater. 2024 Jun;181:222-234. doi: 10.1016/j.actbio.2024.04.031. Epub 2024 Apr 20.
Polymeric biomedical implants are an important clinical tool, but degradation remains difficult to determine post-implantation. Computed tomography (CT) could be a powerful tool for device monitoring, but polymers require incorporation of radiopaque contrast agents to be distinguishable from tissue. In addition, immune response to radiopaque devices must be characterized as it modulates device function. Radiopaque devices and films were produced by incorporating 0-20 wt% TaO nanoparticles into polymers: polycaprolactone (PCL) and poly(lactide-co-glycolide) (PLGA). In vitro inflammatory responses of mouse bone marrow-derived macrophages to polymer matrix incorporating TaO nanoparticles was determined by monitoring cytokine secretion. Nanoparticle addition stimulated a slight inflammatory reaction, increasing TNFα secretion, mediated by changes in polymer matrix properties. Subsequently, devices (PLGA 50:50 + 20 wt% TaO) were implanted subcutaneously in a mouse model of chronic inflammation, that featured a sustained increase in inflammatory response local to the implant site over 12 weeks. No changes to device degradation rates or foreign body response were noted between a normal and chronically stimulated inflammatory environment. Serial CT device monitoring post-implantation provided a detailed timeline of device collapse, with no rapid, spontaneous release of nanoparticles that occluded matrix visualization. Importantly, repeat CT sessions did not ablate the immune system or alter degradation kinetics. Thus, polymer devices incorporating radiopaque nanoparticles can be used for in situ monitoring and be readily combined with other medical imaging techniques, for a dynamic view biomaterial and tissue interactions. STATEMENT OF SIGNIFICANCE: A growing number of implantable devices are in use in the clinic, exposing patients to inherent risks of implant movement, collapse, and infection. The ability to monitor implanted devices would enable faster diagnosis of failure and open the door for personalized rehabilitation therapies - both of which could vastly improve patient outcomes. Unfortunately, polymeric materials which make up most biomedical devices are not radiologically distinguishable from tissue post-implantation. The introduction of radiopaque nanoparticles into polymers allows for serial monitoring via computed tomography, without affecting device degradation. Here we demonstrate for the first time that nanoparticles do not undergo burst release from devices post-implantation and that inflammatory responses - a key determinant of device function in vivo - are also unaffected by nanoparticle addition.
高分子生物医学植入物是一种重要的临床工具，但在植入后降解情况仍然难以确定。计算机断层扫描（CT）可以成为一种强大的设备监测工具，但聚合物需要掺入不透射线的造影剂才能与组织区分开来。此外，必须对免疫反应进行特征描述，因为它会调节设备的功能。通过将 0-20wt%氧化钽纳米颗粒掺入聚合物：聚己内酯（PCL）和聚（乳酸-共-乙醇酸）（PLGA）来制备不透射线的设备和薄膜。通过监测细胞因子分泌来确定小鼠骨髓来源的巨噬细胞对掺入 TaO 纳米颗粒的聚合物基质的体外炎症反应。纳米颗粒的添加刺激了轻微的炎症反应，增加了 TNFα 的分泌，这是由聚合物基质特性的变化介导的。随后，将设备（PLGA50:50+20wt%氧化钽）植入慢性炎症的小鼠模型的皮下，在 12 周的时间内，植入部位的炎症反应持续增加。在正常和慢性刺激的炎症环境中，没有观察到设备降解率或异物反应的变化。植入后连续 CT 设备监测提供了设备崩溃的详细时间表，没有纳米颗粒的快速、自发释放，从而阻止了基质可视化。重要的是，重复 CT 不会使免疫系统消融或改变降解动力学。因此，掺入不透射线纳米颗粒的聚合物设备可用于原位监测，并可与其他医学成像技术相结合，以获得生物材料和组织相互作用的动态视图。意义声明：越来越多的可植入设备在临床中使用，使患者面临着固有风险，包括植入物移动、塌陷和感染。对植入设备进行监测将能够更快地诊断故障，并为个性化康复治疗开辟道路-这两者都可以极大地改善患者的预后。不幸的是，构成大多数生物医学设备的高分子材料在植入后与组织在射线照相上无法区分。将不透射线的纳米颗粒引入聚合物中允许通过计算机断层扫描进行连续监测，而不会影响设备的降解。在这里，我们首次证明，纳米颗粒不会在植入后从设备中快速释放，并且炎症反应-体内设备功能的关键决定因素-也不会因纳米颗粒的添加而受到影响。
