Lian Qiang, Zheng Shaowei, Shi Zhe, Li Kangxian, Chen Rong, Wang Pinkai, Liu Haibing, Chen Yuhang, Zhong Qiang, Liu Qi, Pan Xin, Gao Jian, Gao Chenghao, Liu Weilu, Wu Xuanpin, Zhang Yayun, Zhang Yang, Wang Jian, Cheng Hao
Department of Orthopedic, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Department of Orthopedic, Huizhou First Hospital, Guangdong Medical University, Huizhou 516003, China; Department of Orthopedic, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Acta Biomater. 2022 Dec;154:650-666. doi: 10.1016/j.actbio.2022.10.033. Epub 2022 Oct 25.
Titanium (Ti) implant-associated infections are a challenge in orthopedic surgery, for which a series of antibacterial coatings have been designed and fabricated to reduce the risk of bacterial contamination. Herein, we created a degradable three-layer sandwich-type coating to achieve long-term antibacterial effects while simultaneously reconstructing the local immune microenvironment. The vancomycin (Van)-loaded vaterite coating constitutes the outer and inner layers, whereas Interleukin-12 (IL-12)-containing liposomes embedded in sodium alginate constitutes the middle layer. Van, released from the vaterite, demonstrated a favorable and rapid bactericidal ability against the representative methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains. The released IL-12 exhibited the desired immune reconstitution abilities, actively facilitating defenses against subsequent bacterial invasions. Furthermore, the biocompatibility and cell-binding feature of the multifunctional coating was beneficial for achieving solid interface intergradation. Overall, the benefits of the three-layer sandwich-type coating, including the convenient fabrication process, efficient antimicrobial activity, fast immune remodeling property, fine cell-binding feature, and biodegradability, highlight its promising translational potential in preventing implant infection. STATEMENT OF SIGNIFICANCE: To prevent titanium implant infections, researchers have designed various antibacterial coatings. However, most of these coatings focused only on killing the invading bacteria over a limited postoperative period. However, the local immune microenvironment is compromised during surgery. Local immune deflection impedes the ability of the local immune defenses to clear bacteria and limits immune memory building from active defense against long-term subsequent bacterial invasions. Furthermore, these coatings are usually nondegradable and differ substantially from bone components, thereby impairing the integration of the coating and bone interface and generating concerns about implant stability and bacterial contamination. In this work, we synthesized a degradable coating that provides sustained antibacterial activity, promotes immune reconstitution, and simultaneously achieves solid bone integration.
钛（Ti）植入物相关感染是骨科手术中的一项挑战，针对这一问题，人们设计并制造了一系列抗菌涂层，以降低细菌污染风险。在此，我们制备了一种可降解的三层三明治型涂层，以实现长期抗菌效果，同时重建局部免疫微环境。负载万古霉素（Van）的球霰石涂层构成外层和内层，而包埋在海藻酸钠中的含白细胞介素-12（IL-12）脂质体构成中间层。从球霰石中释放的Van对代表性的甲氧西林敏感金黄色葡萄球菌（MSSA）和耐甲氧西林金黄色葡萄球菌（MRSA）菌株显示出良好且快速的杀菌能力。释放的IL-12表现出预期的免疫重建能力，积极促进对后续细菌入侵的防御。此外，多功能涂层的生物相容性和细胞结合特性有利于实现牢固的界面融合。总体而言，三层三明治型涂层的优势，包括简便的制备工艺、高效的抗菌活性、快速的免疫重塑特性、良好的细胞结合特性和可生物降解性，突出了其在预防植入物感染方面具有广阔的转化应用潜力。重要意义声明：为预防钛植入物感染，研究人员设计了各种抗菌涂层。然而，这些涂层大多仅专注于在有限的术后时间段内杀死入侵细菌。然而，手术过程中局部免疫微环境会受到损害。局部免疫偏差阻碍了局部免疫防御清除细菌的能力，并限制了从对长期后续细菌入侵的主动防御中建立免疫记忆。此外，这些涂层通常不可降解，与骨成分有很大差异，从而损害了涂层与骨界面的整合，并引发了对植入物稳定性和细菌污染的担忧。在这项工作中，我们合成了一种可降解涂层，该涂层具有持续的抗菌活性，促进免疫重建，同时实现牢固的骨整合。
