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亚微米级颗粒连续输注体外模型的验证与定量分析

Validation and quantification of an in vitro model of continuous infusion of submicron-sized particles.

作者信息

Ortiz Steven G, Ma Ting, Epstein Noah J, Smith R Lane, Goodman Stuart B

机构信息

The Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.

出版信息

J Biomed Mater Res B Appl Biomater. 2008 Feb;84(2):328-33. doi: 10.1002/jbm.b.30875.

DOI:10.1002/jbm.b.30875
PMID:17595028
Abstract

Wear particles produced from total joint replacements have been shown to stimulate a foreign body and chronic inflammatory reaction that results in periprosthetic osteolysis. Most animal models that simulate these events have used a single injection of particles, which is not representative of the clinical scenario, in which particles are continuously generated. The goal of this study was to evaluate the feasibility of an osmotic pump for the continuous delivery of clinically relevant submicron-sized particles over an extended period of time. Blue-dyed polystyrene particles and retrieved ultra-high molecular weight polyethylene (UHMWPE) particles, both suspended in mouse serum, were loaded into an Alzet mini-osmotic pump. Pumps were attached to vinyl tubing that ended with hollow titanium rods, simulating a metal implant, which was suspended in a collection vessel. The number of particles collected was evaluated over 2- and 4-week time periods. Delivery of both the polystyrene and UHMWPE particles was feasible over pump concentrations of 10(9) to 10(11) particles per pump. Furthermore, delivery efficiency of polystyrene particles decreased with increasing initial particle concentration, whereas delivery efficiency of UHMWPE particles increased slightly with increasing initial particle concentration. For UHMWPE, approximately one-third of the particles in the pump were collected at 4 weeks. This in vitro study has quantified the efficiency of a unique particle pumping system that may be used in future in vivo investigations to develop a murine model of continuous particle infusion.

摘要

全关节置换产生的磨损颗粒已被证明会引发异物和慢性炎症反应,进而导致假体周围骨溶解。大多数模拟这些情况的动物模型使用单次注射颗粒,这并不代表颗粒持续产生的临床情况。本研究的目的是评估渗透泵在较长时间内持续输送具有临床相关性的亚微米级颗粒的可行性。将悬浮于小鼠血清中的蓝色染色聚苯乙烯颗粒和回收的超高分子量聚乙烯(UHMWPE)颗粒装入Alzet微型渗透泵。泵连接到以空心钛棒为末端的乙烯基管上,模拟金属植入物,该金属植入物悬浮在收集容器中。在2周和4周的时间段内评估收集到的颗粒数量。在每个泵10⁹至10¹¹个颗粒的泵浓度范围内,聚苯乙烯颗粒和UHMWPE颗粒的输送都是可行的。此外,聚苯乙烯颗粒的输送效率随初始颗粒浓度的增加而降低,而UHMWPE颗粒的输送效率随初始颗粒浓度的增加略有增加。对于UHMWPE,在4周时收集到泵中约三分之一的颗粒。这项体外研究量化了一种独特的颗粒泵送系统的效率,该系统未来可能用于体内研究,以建立连续颗粒注入的小鼠模型。

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