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There is significant interest in anti-infective biomaterials that have dual properties of promoting tissue integration and inhibiting bacterial adhesion to prevent device associated infection. However, it is also known that bacteria such as S. aureus have abundant surface pathogen-associated molecular patterns can readily interact with mammalian cells such as osteoblasts. Using tissue culture plastic, we found that S. aureus were electrostatically repelled from this surface and that when they were inoculated onto this surface pre-seeded with MC3T3-E1, they formed aggregates that adhered strongly to these osteoblastic cells. Importantly, the bacteria in the aggregates were more resistant to gentamicin compared to those in bacterial monoculture. This finding thus suggested that the bacteria repelled from such a surface might end up establishing biofilm-like community on adjacent mammalian cells or tissue and that anti-infective biomaterials should actively kill bacteria.

生物醫用材料表面性能,包括表面形貌與化學組成,對誘導骨組織形成并形成骨整合具有重要作用。細胞行為對基底表面形貌和組成的依賴性決定了設計不同功能表面的重要性。作者小組多年來從事生物材料表面微納結構相關研究。在微圖形方面,結合微加工和磁控濺射技術制備出的羥基磷灰石微溝槽;采用溶膠-凝膠與復制微模塑相結合的方法制備了TiO2微圖形;采用掩模曝光電化學微加工技術和噴射電化學微加工技術,在鈦基底上制備多孔微圖形;通過轉移微模塑法與自組裝技術相結合,得到殼聚糖與牛血清蛋白復合微圖形。在納米結構方面,采用電化學陽極氧化處理,獲得一定管徑和管長的二氧化鈦納米管。在微納多級結構方面,結合高壓微弧氧化和低壓陽極氧化制備了微納多級結構鈦表面。除了考慮微納結構單獨效應之外,還考慮了微納結構化與生物功能化的協同效應,即在具有微納結構的生物材料表面通過層層自組裝等手段進行生物化學修飾。最后通過成骨相關細胞培養實驗及體內植入實驗,考察各試樣的生物活性。研究表明,微米尺度表面促進骨細胞粘附、增殖、分化等,而納米尺寸結構以及微納多級結構對細胞功能具有進一步促進作用。微納結構化與表面功能化修飾存在有協同效應。這些研究結果為微納米技術應用于人體植入研究提供了新方向。Surface properties including topography and chemistry are of great significance in deciding the response of tissue to implants. Our group has been engaged in researches on micro/nano structured biomaterial surfaces for a long time. This article reviews our series works on osteogenetic cells behavior on biomaterial surfaces with micro-and nano-structures. For micro-patterns, hydroxyapatite microgrooves were prepared by combining micro-fabrication technology and magnetron sputtering technology; TiO2 micropatterns were obtained by combining sol-gel and replica molding; Micro-patterned Ti substrates were prepared by using a through mask electrochemical micromachining and a jet electrochemical micromachining technology; chitosan/bovine serum albumin micropatterns were prepared on functionalized Ti surfaces by micro-transfer molding combined with self-assembly. For nanostructures, titania nanotubes with various diameters and lengths were prepared by a electrochemical anodic oxidation treatment. For micro-nano hierarchical structures, titania micropores modified with nanotubes were obtained by high voltage micro-arc oxidation and low voltage anodization. In addition to considering the effects of micro-nano structure alone, the synergistic effects of struturalization and biofunctionalization of biomaterial surfaces were investigated, which were realized through layer-by-layer self-assembly and other means of biochemical modification on micro/nano structured surf