Department of Orthopaedics, Case Western Reserve University, Cleveland, OH 44106, USA.
Bone. 2013 Jan;52(1):93-101. doi: 10.1016/j.bone.2012.09.011. Epub 2012 Sep 17.
Osseointegration is the process by which an orthopedic implant makes direct bone-to-implant contact and is crucial for the long-term function of the implant. Surface contaminants, such as bacterial debris and manufacturing residues, may remain on orthopedic implants after sterilization and impair osseointegration. For example, specific lots of implants that were associated with impaired osseointegration and high failure rates were discovered to have contaminants including bacterial debris. Therefore, the goals of this study were to determine if bacterial debris exists on sterile orthopedic implants and if adherent bacterial debris inhibits the osseointegration of orthopedic implants. We found that debris containing lipopolysaccharide (LPS) from Gram-negative bacteria exists on both sterile craniofacial implants and wrist implants. Levels of bacterial debris vary not only between different lots of implants but within an individual lot. Using our murine model of osseointegration, we found that ultrapure LPS adherent to the implants inhibited bone-to-implant contact and biomechanical pullout measures. Analysis of osseointegration in knock-out mice demonstrated that adherent LPS inhibited osseointegration by signaling through its primary receptor, Toll-like receptor 4, and not by signaling through Toll-like receptor 2. Ultrapure LPS adherent to titanium alloy discs had no detectable effect on early stages of MC3T3-E1 osteogenesis in vitro such as attachment, spreading or growth. However, later stages of osteogenic differentiation and mineralization were inhibited by adherent LPS. Thus, LPS may inhibit osseointegration in part through cell autonomous effects on osteoblasts. These results highlight bacterial debris as a type of surface contaminant that can impair the osseointegration of orthopedic implants.
骨整合是骨科植入物与骨直接接触的过程，对植入物的长期功能至关重要。在消毒后，骨科植入物表面可能会残留表面污染物，如细菌碎片和制造残留物，并会影响骨整合。例如，发现某些批次的植入物与骨整合受损和高失败率有关，这些植入物含有细菌碎片等污染物。因此，本研究的目的是确定无菌骨科植入物上是否存在细菌碎片，以及是否存在附着的细菌碎片会抑制骨科植入物的骨整合。我们发现，革兰氏阴性菌来源的含脂多糖（LPS）的碎片存在于无菌颅面植入物和腕部植入物上。细菌碎片的水平不仅在不同批次的植入物之间存在差异，而且在同一批次的植入物中也存在差异。使用我们的骨整合小鼠模型，我们发现附着在植入物上的超纯 LPS 抑制了骨与植入物的接触和生物力学拔出测量。对敲除小鼠骨整合的分析表明，附着的 LPS 通过其主要受体 Toll 样受体 4 而不是通过 Toll 样受体 2 发出信号，从而抑制了骨整合。附着在钛合金盘上的超纯 LPS 对体外 MC3T3-E1 成骨作用的早期阶段（如附着、扩散或生长）没有明显影响。然而，成骨分化和矿化的后期阶段受到附着 LPS 的抑制。因此，LPS 可能通过对成骨细胞的自主细胞作用部分抑制骨整合。这些结果强调了细菌碎片作为一种表面污染物，会影响骨科植入物的骨整合。
