Antibacterial Activity in Iodine-coated Implants Under Conditions of Iodine Loss: Study in a Rat Model Plus In Vitro Analysis.

BACKGROUND: We developed iodine-coated titanium implants to suppress microbial activity and prevent periprosthetic joint infection (PJI); their efficacy was demonstrated in animal and in vitro models. The iodine content in iodine-coated implants naturally decreases in vivo. However, to our knowledge, the effect of reduced iodine content on the implant's antimicrobial activity has not been evaluated to date. QUESTIONS/PURPOSES: (1) How much does the iodine content on the implant surface decrease after 4 and 8 weeks in vivo in a rat model? (2) What effect does the reduced iodine content have on the antimicrobial effect of the implant against multiple bacteria in an in vitro model? METHODS: This experiment was performed in two parts: an in vivo experiment to determine attenuation of iodine levels over time in rats, and an in vitro experiment in which we sought to assess whether the reduced iodine content observed in the in vivo experiment was still sufficient to deliver antimicrobial activity against common pathogens seen in PJI. For the in vivo experiment, three types of titanium alloy washers were implanted in rats: untreated (Ti), surface-anodized to produce an oxide film (Ti-O), and with an iodine layer on the oxidation film (Ti-I). The attenuation of iodine levels in rats was measured over time using inductively coupled plasma-mass spectrometry. Herein, only the Ti-I washer was used, with five implanted in each rat that were removed after 4 or 8 weeks. For the 4- and 8-week models, two rats and 15 washers were used. For the in vitro study, to determine the antibacterial effect, three types of washers (Ti, Ti-O, and Ti-I) (nine washers in total) were implanted in each rat. Then, the washers were removed and the antibacterial effect of each washer was examined on multiple bacterial species using the spread plate method and fluorescence microscopy. For the spread plate method, six rats were used, and five rats were used for the observation using fluorescence microscopy; further, 4- and 8-week models were made for each method. Thus, a total of 22 rats and 198 washers were used. Live and dead bacteria in the biofilm were stained, and the biofilm coverage percentage for quantitative analysis was determined using fluorescence microscopy in a nonblinded manner. Ti-I was used as the experimental group, and Ti and Ti-O were used as control groups. The total number of rats and washers used throughout this study was 24 and 213, respectively. RESULTS: Iodine content in rats implanted with Ti-I samples decreased to 72% and 65% after the in vivo period of 4 and 8 weeks, respectively (p = 0.001 and p < 0.001, respectively). In the in vitro experiment, the Ti-I implants demonstrated a stronger antimicrobial activity than Ti and Ti-O implants in the 4- and 8-week models. Both the median number of bacterial colonies and the median biofilm coverage percentage with live bacteria on Ti-I were lower than those on Ti or Ti-O implants for each bacterial species in the 4- and 8-week models. There was no difference in the median biofilm coverage percentage of dead bacteria. In the 8-week model, the antibacterial activity using the spread plate method had median (interquartile range) numbers of bacteria on the Ti, Ti-O, and Ti-I implants of 112 (104 to 165) × 105, 147 (111 to 162) × 105, and 55 (37 to 67) × 105 of methicillin-sensitive Staphylococcus aureus (Ti-I versus Ti, p = 0.026; Ti-I versus Ti-O, p = 0.009); 71 (39 to 111) × 105, 50 (44 to 62) × 105, and 26 (9 to 31)× 105 CFU of methicillin-resistant S. aureus (Ti-I versus Ti, p = 0.026; Ti-I versus Ti-O, p = 0.034); and 77 (74 to 83) × 106, 111 (95 to 117) × 106, and 30 (21 to 45) × 106 CFU of Pseudomonas aeruginosa (Ti-I versus Ti, p = 0.004; Ti-I versus Ti-O, p = 0.009). Despite the decrease in the iodine content of Ti-I after 8 weeks, it demonstrated better antibacterial activity against all tested bacteria than the Ti and Ti-O implants. CONCLUSION: Iodine-coated implants retained their iodine content and antibacterial activity against methicillin-sensitive S. aureus, methicillin-resistant S. aureus, and P. aeruginosa for 8 weeks in vivo in rats. To evaluate the longer-lasting antibacterial efficacy, further research using larger infected animal PJI models with implants in the joints of both males and females is desirable. CLINICAL RELEVANCE: Iodine-coated titanium implants displayed an antibacterial activity for 8 weeks in rats in vivo. Although the findings in a rat model do not guarantee efficacy in humans, they represent an important step toward clinical application.

Comparison of mid-term clinical results between cementless and cemented femoral stems in total hip arthroplasty with femoral shortening osteotomy for Crowe type IV hips.

INTRODUCTION: This report is the first study to compare the clinical outcomes between cementless and cemented femoral prostheses in total hip arthroplasty (THA) with subtrochanteric femoral shortening osteotomy for Crowe type IV hips. MATERIALS AND METHODS: We identified 26 hips in 20 patients who had undergone cemented (n = 13) or cementless (n = 13) THA with subtrochanteric femoral shortening osteotomy for Crowe type IV hips with a minimum follow-up period of 2 years. The mean follow-up period was 60.8 ± 33.9 months (24-120 months). We compared radiological findings, postoperative clinical recoveries, postoperative complications, and implant survival rates. RESULTS: In both groups, there were no cases of aseptic loosening for the acetabular and femoral implant. In terms of bone union at the osteotomy site, the mean duration was significantly longer in the cemented group (9.8 ± 4.2 months) than in the cementless group (5.0 ± 1.9 months). The clinical hip score in gait and pain at 3 months postoperatively was significantly higher in the cemented group than in the cementless group, while there were no significant changes at other timepoints between two groups. The number of postoperative complications was not significantly different between the two groups. The implant survival rate was 92% in the cementless group and 100% in the cemented group at 5 years postoperatively (P = 0.31). CONCLUSIONS: The cemented femoral prosthesis is superior to the cementless femoral prosthesis for early clinical recovery, while the duration required to achieve bone union at the osteotomy site is longer in the cemented femoral prostheses. It is possible for surgeons to perform successful hip reconstructions, regardless of the fixation method used for THA with shortening femoral osteotomy.

Iodine-supported titanium implants have good antimicrobial attachment effects.

BACKGROUND: We have developed iodine-supported titanium implants, which were shown to have good anti-bacterial effects for Methicillin-sensitive Staphylococcus aureus (MSSA) in our past basic research. However, PJI can be caused by various bacteria including MRSA, Pseudomonas aeruginosa, MSSE, and fungus. The purpose of this study was to investigate whether these implants also have good antibacterial attachment effects for MRSA, P. aeruginosa, MSSE, and fungus. METHODS: Ti-6Al-4V titanium plates were either left untreated (Ti), treated with oxide film on the Ti surface by anodization (Ti-O), or treated with an iodine coating on oxidation film (Ti-I). The antibacterial activity of the TiI was measured by experimental methods according to Japanese Industrial Standard (JIS) protocols. Implants in this study were exposed to MRSA (ATCC43300), P. aeruginosa (ATCC27853), MSSE (ATCC35984), and Candida Albicans (ATCC10231). Colonies were counted immediately after the bacteria attached to the metal surface and again after 24 h incubation. The difference in the number of bacteria on each metal plate was statistically investigated and an antibacterial activity value was calculated. An effective antibacterial active value of more than 2.0 was judged to be effective according to JIS protocol. RESULTS: No countable viable bacteria were observed on the Ti-I surface. For all bacteria there was a significant difference in the mean number of viable bacteria between Ti-I and Ti or Ti-O. Antibacterial activity value in Ti-I and Ti-O was more than 5.9 and 3.6 respectively for MRSA, more than 2.8 and zero for P. aeruginosa, more than 4.3 and zero for MSSE, and more than 4.7 and zero for C. Albicans. CONCLUSIONS: This study showed that iodine-supported titanium implants have good antimicrobial attachment effects for MRSA, P. aeruginosa, MSSE, and C. Albicans. Iodine-supported titanium implants could have great potential as innovative antibacterial implants that can prevent early onset periprosthetic joint infection.

Comparison with the osteoconductivity and bone-bonding ability of the iodine supported titanium, titanium with porous oxide layer and the titanium alloy in the rabbit model.

BACKGROUND: One of the serious postoperative complications associated with joint replacement is bacterial infection. In our recent investigations, iodine supported titanium implants demonstrated antibacterial activity in both in vitro and in vivo studies. The surfaces of the implants have porous anodic oxide layer with the antiseptic properties of iodine. According to the literature the titanium with porous anodic oxide have good osteoconductivity. But it is not clear whether the properties of iodine influence bone bonding of implants. OBJECTIVES: The aim of this study is to evaluate the influence of the properties of iodine and porous anodic oxide layer in the bone bonding ability of titanium implants. STUDY DESIGN & METHODS: Titanium rods were implanted in intramedullary rabbit femur models, in regard to the cementless hip stem. The implant rods were 5 mm in diameter and 25 mm in length. Three types of titanium rods were implanted.One was untreated titanium (control group (CL)), another was titanium with oxide layer without iodine (oxide layer group (OL)), and the other was Iodine treated Titanium (iodine group (ID)). The rods were inserted into the distal femur. We assessed the bonding strength by a measuring pull-out test at 4, 8, and 12 weeks after implantation. The bone-implant interfaces were evaluated at 4 weeks after implantation. RESULTS: Pull-out test results of the ID implants were 202, 355, and 344 N, and those of the OL implants were 220, 310, 329 N at 4, 8, and 12 weeks, significantly higher than those of the CL implants (102, 216, and 227 N). But there were no significant difference in ID implants and OL implants. Histological examination revealed that new bone formed on the surface of each types of implants, but significantly more bone made direct contact with the surfaces of the ID implants and OL implants. CONCLUSIONS: This research showed that new type of coating, iodine coated titanium has low toxicity and good osteoconductivity.

Innovative antimicrobial coating of titanium implants with iodine.

BACKGROUND: Postoperative infection associated with implants remains a serious complication in orthopedic surgery. Several biomaterial surface treatments have been proposed as a means of reducing the incidence of implant-associated infections. In this study, a clinical trial was performed using an iodine-supported titanium that suppresses the microbial activities. METHODS: A total of 222 patients with postoperative infection or compromised status were treated using iodine-supported titanium implants. The mean age of the patients was 49.4 years (range 5-85 years). One hundred twenty-seven patients were male and 95 were female. In 158 patients, iodine-supported implants were used to prevent infection, such as compromised hosts and conditions, and in 64 patients to treat active infection. White blood cell (WBCs) and C-reactive protein (CRP) levels were measured pre- and postoperatively in all patients. To confirm whether iodine from the implant affected physiological functions, thyroid hormone levels in the blood were examined. Both examinations were conducted sequentially for a year. Radiological evaluations were performed regularly after the operation. The chronological changes of the iodine amount were evaluated using half pins removed after completion of external fixation. RESULTS: The mean follow-up period was 18.4 months (range 3-44 months). Acute infection developed in three tumor cases among the 158 patients on preventive therapy. All three recovered without removal of the implants. Infection was cured in all 64 patients with infection. Median WBC levels were in the normal range, and median CRP levels returned to <0.5 within 4 weeks after surgery. Abnormalities of thyroid gland function were not detected. None of the patients experienced loosening of the implants. There were two patients with mechanical implant failure, which was treated by re-implantation. Excellent bone ingrowth and ongrowth were found around all hip and tumor prostheses. One year later, the amount of iodine on external fixation pins remained about 20-30%. CONCLUSIONS: Iodine-supported titanium implants can be very effective for preventing and treating infections after orthopedic surgery. Cytotoxicity and adverse effects were not detected.

Polyneuropathy caused by cobalt-chromium metallosis after total hip replacement.

Although metal intoxication after arthroplasty causes various symptoms, polyneuropathy has never been the focus of clinical investigation. We report the case of a 56-year-old woman with metal neuropathy. She had metallosis after hip arthroplasty with a cobalt-chromium alloy prosthesis. She developed progressive sensory disturbance, hearing loss, and hypothyroidism. Sural nerve biopsy indicated axonopathy. After exchange arthroplasty, blood levels of cobalt and chromium decreased, and her symptoms improved. Cobalt or chromium can cause axonopathy.

A mechanical analysis of femoral resurfacing implantation for osteonecrosis of the femoral head.

Hip resurfacing is becoming a popular procedure for treating osteonecrosis of the femoral head. However, the biomechanical changes that occur after femoral resurfacing have not been fully investigated with respect to the individual extent of the necrosis. In this study, we evaluated biomechanical changes at various extents of necrosis and implant alignments using the finite element analysis method. We established 3 patterns of necrosis by depth from the surface of femoral head and 5 stem angles. For these models, we evaluated biomechanical changes associated with the extent of necrosis and the stem alignment. Our results indicate that stress distribution near the bone-cement interface increased with expansion of the necrosis. The maximum stress on the prosthesis was decreased with stem angles ranging from 130° to 140°. The peak stress of cement increased as the stem angle became varus. This study indicates that resurfacing arthroplasty will have adverse biomechanical effects when there is a large extent of osteonecrosis and excessive varus or valgus implantation of the prosthesis.