Joe Kodama1, Hongfang Chen2, Tangjun Zhou2, Junichi Kushioka1, Rintaro Okada1, Hiroyuki Tsukazaki1, Daisuke Tateiwa1, Shinichi Nakagawa1, Yuichiro Ukon1, Zeynep Bal1, Haijun Tian3, Jie Zhao4, Takashi Kaito5. 1. Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. 2. Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China. 3. Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China. Electronic address: haijuntianmd@gmail.com. 4. Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China. Electronic address: profzhaojie@126.com. 5. Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: takashikaito@ort.med.osaka-u.ac.jp.
Abstract
BACKGROUND CONTEXT: Infection around intervertebral fusion cages can be intractable because of the avascular nature of the intervertebral disc space. Intervertebral cages with antibacterial effects may be a method by which this complication can be prevented. PURPOSE: To investigate the bacterial load on the antibacterial coating cages for spinal interbody fusion STUDY DESIGN: An experimental in vitro and in vivo study. METHODS: Based on the micro-computed tomography (CT) data of rat caudal discs, mesh-like titanium (Ti) cages that anatomically fit into the discs were fabricated by three-dimensional (3D) printing. Additionally, an antibacterial coating was applied with quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC). In vitro release kinetics of the HACC was performed, and the antibacterial performance of the HACC-coated (Ti-HACC) cages (via inhibition zone assay, bacterial adhesion assay, and biofilm formation assay) was evaluated. Then, Ti-HACC- or noncoated (Ti) cages were implanted in the caudal discs of rats with bioluminescent Staphylococcus aureus. Bacterial survival was investigated using an in vivo imaging system (IVIS) on postoperative days 1, 3, and 5. On day 5, the infection-related changes (bone destruction and migration of cages) were assessed using micro-CT, and the healing status of the surgical wounds was also assessed. After the removal of the cages, the quantification of bacteria attached to the cages was obtained by IVIS. Histological evaluation was performed by hematoxylin and eosin staining and TRAP (tartrate-resistant acid phosphatase) staining. RESULTS: Release kinetic analysis showed the sustained release of HACC over 3 days from Ti-HACC cages. Antibacterial effects of Ti-HACC cages were demonstrated in all in vitro assays. IVIS evaluation indicated that the in vivo implantation of Ti-HACC cages with S. aureus exhibited better wound healing, less infection-related changes on micro-CT, and reduced bacterial quantity in the extracted cages compared to Ti cages. Histological evaluation demonstrated an increased number of TRAP-positive osteoclasts and severe bone destruction in the rats treated with Ti cages. CONCLUSIONS: We developed a novel antibacterial HACC-coated intervertebral cage that exhibited prominent antibacterial efficacy and prevented the structural damage caused by the infection in rat caudal discs. CLINICAL SIGNIFICANCE: HACC-coated titanium intervertebral cages may be a promising option for preventing intractable postoperative infection in spinal interbody fusion surgery.
BACKGROUND CONTEXT: Infection around intervertebral fusion cages can be intractable because of the avascular nature of the intervertebral disc space. Intervertebral cages with antibacterial effects may be a method by which this complication can be prevented. PURPOSE: To investigate the bacterial load on the antibacterial coating cages for spinal interbody fusion STUDY DESIGN: An experimental in vitro and in vivo study. METHODS: Based on the micro-computed tomography (CT) data of rat caudal discs, mesh-like titanium (Ti) cages that anatomically fit into the discs were fabricated by three-dimensional (3D) printing. Additionally, an antibacterial coating was applied with quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC). In vitro release kinetics of the HACC was performed, and the antibacterial performance of the HACC-coated (Ti-HACC) cages (via inhibition zone assay, bacterial adhesion assay, and biofilm formation assay) was evaluated. Then, Ti-HACC- or noncoated (Ti) cages were implanted in the caudal discs of rats with bioluminescent Staphylococcus aureus. Bacterial survival was investigated using an in vivo imaging system (IVIS) on postoperative days 1, 3, and 5. On day 5, the infection-related changes (bone destruction and migration of cages) were assessed using micro-CT, and the healing status of the surgical wounds was also assessed. After the removal of the cages, the quantification of bacteria attached to the cages was obtained by IVIS. Histological evaluation was performed by hematoxylin and eosin staining and TRAP (tartrate-resistant acid phosphatase) staining. RESULTS: Release kinetic analysis showed the sustained release of HACC over 3 days from Ti-HACC cages. Antibacterial effects of Ti-HACC cages were demonstrated in all in vitro assays. IVIS evaluation indicated that the in vivo implantation of Ti-HACC cages with S. aureus exhibited better wound healing, less infection-related changes on micro-CT, and reduced bacterial quantity in the extracted cages compared to Ti cages. Histological evaluation demonstrated an increased number of TRAP-positive osteoclasts and severe bone destruction in the rats treated with Ti cages. CONCLUSIONS: We developed a novel antibacterial HACC-coated intervertebral cage that exhibited prominent antibacterial efficacy and prevented the structural damage caused by the infection in rat caudal discs. CLINICAL SIGNIFICANCE: HACC-coated titanium intervertebral cages may be a promising option for preventing intractable postoperative infection in spinal interbody fusion surgery.
Authors: Joana C Antunes; Joana M Domingues; Catarina S Miranda; A Francisca G Silva; Natália C Homem; M Teresa P Amorim; Helena P Felgueiras Journal: Mar Drugs Date: 2021-06-23 Impact factor: 5.118