Pilge Hakan, Fröbel Julia, Lensing-Höhn Sabine, Zilkens Christoph, Krauspe Rüdiger
Department of Orthopaedic Surgery, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
Biomed Res Int. 2016;2016:2042687. doi: 10.1155/2016/2042687. Epub 2016 Mar 16.
Drugs may have a significant effect on postoperative bone healing by reducing the function of human mesenchymal stromal cells (hMSC) or mature osteoblasts. Although cefazolin is one of the most commonly used antibiotic drugs in arthroplasty to prevent infection worldwide, there is a lack of information regarding how cefazolin affects hMSC and therefore may have an effect on early bone healing. We studied the proliferation and migration capacity of primary hMSC during cefazolin treatment at various doses for up to 3 days, as well as the reversibility of the effects during the subsequent 3 days of culture without the drug. We found a time- and dose-dependent reduction of the proliferation rate and the migratory potential. Tests of whether these effects were reversible revealed that doses ≥ 250 μg/mL or treatments longer than 24 h irreversibly affected the cells. We are the first to show that application of cefazolin irreversibly inhibits the potential of hMSC for migration to the trauma site and local proliferation. Cefazolin should be administered only at the required dosage and time to prevent periprosthetic infection. If long-term administration is required and delayed bone healing is present, cefazolin application must be considered as a cause of delayed bone healing.
药物可能通过降低人间充质基质细胞（hMSC）或成熟成骨细胞的功能，对术后骨愈合产生显著影响。尽管头孢唑林是全球关节置换术中最常用的预防感染的抗生素药物之一，但关于头孢唑林如何影响hMSC以及因此可能对早期骨愈合产生何种影响，目前尚缺乏相关信息。我们研究了在不同剂量头孢唑林处理长达3天的过程中，原代hMSC的增殖和迁移能力，以及在随后无药物培养的3天内这些影响的可逆性。我们发现增殖率和迁移潜能呈时间和剂量依赖性降低。关于这些影响是否可逆的测试表明，剂量≥250μg/mL或处理时间超过24小时会对细胞产生不可逆影响。我们首次表明，应用头孢唑林会不可逆地抑制hMSC迁移至创伤部位和局部增殖的潜能。头孢唑林应仅按所需剂量和时间给药以预防假体周围感染。如果需要长期给药且存在骨愈合延迟的情况，必须考虑应用头孢唑林是导致骨愈合延迟的一个原因。
