Long-term antibacterial activity of vancomycin from calcium phosphate cement in vivo.

BACKGROUND: Periprosthetic joint infection is a major complication of total joint arthroplasty, with treatment requiring a two-stage exchange procedure and 6 weeks of systemic antibiotics. However, depending on the infection site, intravenous delivery of antibiotics like vancomycin (VCM) can have poor tissue transferability, thus reducing their therapeutic effect. OBJECTIVE: This study demonstrates the 24-week in vivo release profile and antibacterial activity of VCM from calcium phosphate cement impregnated with VCM (CPC/VCM) and compares them with those from polymethylmethacrylate impregnated with VCM (PMMA/VCM). METHODS: Rats were implanted with the test specimens between the fascia and quadriceps. After implantation for 24 weeks, the test specimens were removed and residual VCM was extracted to calculate the concentration of VCM released into rat tissues. We also examined the antibacterial activity of releasable VCM from the removed test specimens by placing them directly onto the surface of agar. RESULTS: CPC/VCM released greater concentrations of VCM for a longer period of time within the 24 weeks than PMMA/VCM. Moreover, CPC/VCM released 1.4 to 26.1-fold more VCM than PMMA/VCM. Using Staphylococcus aureus, antibacterial activity was logarithmically correlated with VCM concentration across the entire concentration range tested (12.5-800 µg/mL). While the area within which inhibition was observed-the inhibition zone-for both CPC/VCM and PMMA/VCM formed and gradually shrank with time after implantation, that for CPC/VCM was significantly larger than that for PMMA/VCM in each week after implantation. CONCLUSION: CPC/VCM releases greater amounts of VCM with antibacterial activity for longer periods of time than PMMA/VCM, suggesting that CPC is effective for facilitating the release of antibiotics for local action in patients with established postoperative infection.

Osteoinduction in Novel Micropores of Partially Dissolved and Precipitated Hydroxyapatite Block in Scalp of Young Rats.

Osteoinduction in muscles by porous ceramics has been reported to be a real phenomenon. In this study, osteoinduction in connective tissues was found in highly porous hydroxyapatite (HAp) ceramics with large specific surface areas. We have developed the combination method of the partial dissolution-precipitation (PDP) technique involving the stirring-supersonic treatment in 1.7 × 10-2 N HNO3 solution containing Ca2+ and PO43- to improve the surface and the bulk of commercially available synthetic HAp block (82.5% in porosity, 50-300 µm in pore size). The modified HAp was named as a partially dissolved and precipitated HAp (PDP-HAp). The PDP-HAp exhibited the porosities of 85-90%, the macropore sizes of 50-200 µm, and the specific surface areas of 1.0-2.0 m2/g, with microcracks. The aim of this study was to observe bone induction by the PDP-HAp with or without BMP-2 in scalp tissues of four-week-old rats. Young rats were divided into the PDP-HAp alone group and the PDP-HAp/BMP-2 group for a long-term observation. In the PDP-HAp group, bone induction occurred inside the many pores at nine months, and the ratio of induced bone was 12.0%. In the PDP-HAp/BMP-2 group, bone induction occurred in almost all pores at three months, and compact bone was found at nine months. The ratios of induced bone were 77.0% at three months and 86.0% at nine months. We believe that osteoinduction by the PDP-HAp might be different from the process of BMP-loaded HAp-induced bone formation, because the PDP-HAp has osteogenic microporous compartments with partially absorbable HAp crystals. The PDP technique may contribute to create bioceramics with osteoinductive property for bone regenerative medicine.

Augmentation of fracture healing by hydroxyapatite/collagen paste and bone morphogenetic protein-2 evaluated using a rat femur osteotomy model.

In fracture treatment, biological bone union generally depends on the bone's natural fracture healing capacity, even in surgically treated cases. Hydroxyapatite/collagen composite (HAp/Col) has high osteoconductivity and stimulates osteogenic progenitors. Furthermore, it has the potent capacity to adsorb bone morphogenetic proteins (BMPs). In this study, we prepared an injectable HAp/Col paste and evaluated its augmentation of bone union. Furthermore, the effect of HAp/Col paste combined with BMP-2 was also evaluated. We used a rat femur osteotomy model with a defect size of 1 mm. Male Wistar rats were assigned to one of the following four groups; a control group without any implant, a HAp/Col implant group, a group that received an absorbable collagen sponge (ACS) implant impregnated with BMP-2 (1 µg), and a group that received a HAp/Col implant impregnated with BMP-2 implant. Micro-CT analysis, three-point bending tests, and histological evaluation were performed. Bone union was achieved in two of eight cases in the HAp/Col group, five of eight cases in the ACS + BMP-2 group, and all cases in the HAp/Col + BMP-2 group at 8 weeks post-surgery. The control group did not achieve bone union. In addition, in the HAp/Col + BMP-2 group, the biomechanical strength of the fused femurs was comparable to that of the contralateral intact femur; the ratio of the mechanical load at the breaking point of the osteotomy side relative to that of the contralateral side was 1.00 ± 0.151 (SD). These results indicate that HAp/Col paste with or without BMP-2 augments bone union. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:129-137, 2018.

In Vivo Release of Vancomycin from Calcium Phosphate Cement.

Calcium phosphate cement (CPC) has good release efficiency and has therefore been used as a drug delivery system for postoperative infection. The release profile of CPC has mainly been evaluated by in vitro studies, which are carried out by immersing test specimens in a relatively large amount of solvent. However, it remains unclear whether antibiotic-impregnated CPC has sufficient clinical effects and release in vivo. We examined the in vivo release profile of CPC impregnated with vancomycin (VCM) and compared this with that of polymethylmethacrylate (PMMA) cement. To evaluate the release profile in vitro, the test specimens were immersed in 10 mL sterile phosphate-buffered saline per gram of test specimen and incubated at 37°C for 56 days in triplicate. For in vivo experiments, the test specimens were implanted between the fascia and muscle of the femur of rats. Residual VCM was extracted from the removed test specimens to determine the amount of VCM released into rat tissues. CPC released more VCM over a longer duration than PMMA in vitro. Released levels of VCM from CPC/VCM in vivo were 3.4-fold, 5.0-fold, and 8.6-fold greater on days 1, 7, and 28, respectively, than those released on the corresponding days from PMMA/VCM and were drastically greater on day 56 due to inefficient release from PMMA/VCM. The amount of VCM released from CPC and PMMA was much higher than the minimum inhibitory concentration (1.56 µg) and lower than the detection limit, respectively. Our findings suggest that CPC is a suitable material for releasing antibiotics for local action against established postoperative infection.

Bilateral open-door cervical expansive laminoplasty with hydroxyapatite spacers and titanium screws.

OBJECT: The authors report a simple method for bilateral open-door cervical expansive laminoplasty in which hydroxyapatite (HA) spacers are secured by titanium screws. A biomechanical study was also conducted to confirm the strength of the screw fixation. METHODS: A unilateral posterior approach was used to allow preservation of the posterior supporting elements (the posterior tension band) until the laminae were cut at the base. A bilateral open-door expansive laminotomy was then performed in standard fashion. Appropriate-sized HA spacers were selected, held with a specially designed holder, and placed between the split laminae. The screw holes were made in the laminae along the direction of the screw holes in the spacer, and two screws were inserted ventrolaterally to the laminae, resulting in instantaneous fixation. This procedure was performed in 15 patients; clinical results were successful, and there were no significant intraoperative complications. Follow-up radiological studies revealed no evidence of displacement of the spacers or screw backout. The screw artifacts observed on magnetic resonance imaging were minimal, allowing evaluation of the cervical spinal cord. The sagittal alignment of the cervical spine was well preserved. In the biomechanical studies the authors found that the screw fixation was of satisfactory strength, compared with other methods of fixation. CONCLUSIONS: Bilateral open-door cervical expansive laminoplasty in which HA spacers are secured by titanium screws is a simple and quick method that yields sufficient fixation strength.