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

2021 ◽  
pp. 1-10
Author(s):  
Manabu Mukai ◽  
Kentaro Uchida ◽  
Ken Sugo ◽  
Masanori Nakasu ◽  
Takehiko Nakajima ◽  
...  

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.

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Kentaro Uchida ◽  
Ken Sugo ◽  
Takehiko Nakajima ◽  
Mitsufumi Nakawaki ◽  
Shotaro Takano ◽  
...  

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.


Author(s):  
Akiyoshi Shimatani ◽  
Hiromitsu Toyoda ◽  
Kumi Orita ◽  
Yuta Ibara ◽  
Yoshiyuki Yokogawa ◽  
...  

AbstractThis study investigated whether mixing low viscosity alginic acid with calcium phosphate cement (CPC) causes interconnected porosity in the CPC and enhances bone replacement by improving the biological interactions. Furthermore, we hypothesized that low viscosity alginic acid would shorten the setting time of CPC and improve its strength. CPC samples were prepared with 0, 5, 10, and 20% low viscosity alginic acid. After immersion in acetate buffer, possible porosification in CPC was monitored in vitro using scanning electron microscopy (SEM), and the setting times and compressive strengths were measured. In vivo study was conducted by placing CPC in a hole created on the femur of New Zealand white rabbit. Microcomputed tomography and histological examination were performed 6 weeks after implantation. SEM images confirmed that alginic acid enhanced the porosity of CPC compared to the control, and the setting time and compressive strength also improved. When incorporating a maximum amount of alginic acid, the new bone mass was significantly higher than the control group (P = 0.0153). These biological responses are promising for the translation of these biomaterials and their commercialization for clinic applications.


2007 ◽  
Vol 330-332 ◽  
pp. 1091-1094
Author(s):  
H. Kim ◽  
M. Park ◽  
Su Young Lee ◽  
Kang Yong Lee ◽  
Hyun Min Kim ◽  
...  

Demineralized bone matrix (DBM)-calcium phosphate cement (CPC) composites were subjected to cellular test of osteogenic potentials and implantation in animal model. The expression of osteogenic marker gene from mouse preosteoblast cell line MC3T3-E1 adhered to the DBM-CPC composite was much higher than plain CPC. In addition, the DBM-CPC composite implanted nude mice revealed osteoinduction between the implanted composite and adjacent tissues, whereas the plain CPC induced osteoconduction.


Polymers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 3075
Author(s):  
Sok Kuan Wong ◽  
Yew Hoong Wong ◽  
Kok-Yong Chin ◽  
Soelaiman Ima-Nirwana

Calcium phosphate cement (CPC) is a promising material used in the treatment of bone defects due to its profitable features of self-setting capability, osteoconductivity, injectability, mouldability, and biocompatibility. However, the major limitations of CPC, such as the brittleness, lack of osteogenic property, and poor washout resistance, remain to be resolved. Thus, significant research effort has been committed to modify and reinforce CPC. The mixture of CPC with various biological materials, defined as the materials produced by living organisms, have been fabricated by researchers and their characteristics have been investigated in vitro and in vivo. This present review aimed to provide a comprehensive overview enabling the readers to compare the physical, mechanical, and biological properties of CPC upon the incorporation of different biological materials. By mixing the bone-related transcription factors, proteins, and/or polysaccharides with CPC, researchers have demonstrated that these combinations not only resolved the lack of mechanical strength and osteogenic effects of CPC but also further improve its own functional properties. However, exceptions were seen in CPC incorporated with certain proteins (such as elastin-like polypeptide and calcitonin gene-related peptide) as well as blood components. In conclusion, the addition of biological materials potentially improves CPC features, which vary depending on the types of materials embedded into it. The significant enhancement of CPC seen in vitro and in vivo requires further verification in human trials for its clinical application.


Orthopedics ◽  
2009 ◽  
Vol 32 (1) ◽  
pp. 27-6 ◽  
Author(s):  
Zhiping Yang ◽  
Dong Li ◽  
Jian Han ◽  
Jianmin Li ◽  
Xin Li ◽  
...  

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Rania M. Khashaba ◽  
Mervet M. Moussa ◽  
Donald J. Mettenburg ◽  
Frederick A. Rueggeberg ◽  
Norman B. Chutkan ◽  
...  

New polymeric calcium phosphate cement composites (CPCs) were developed. Cement powder consisting of 60 wt% tetracalcium phosphate, 30 wt% dicalcium phosphate dihydrate, and 10 wt% tricalcium phosphate was combined with either 35% w/w poly methyl vinyl ether maleic acid or polyacrylic acid to obtain CPC-1 and CPC-2. The setting time and compressive and diametral tensile strength of the CPCs were evaluated and compared with that of a commercial hydroxyapatite cement.In vitrocytotoxicity andin vivobiocompatibility of the two CPCs and hydroxyapatite cement were assessed. The setting time of the cements was 5–15 min. CPC-1 and CPC-2 showed significantly higher compressive and diametral strength values compared to hydroxyapatite cement. CPC-1 and CPC-2 were equivalent to Teflon controls after 1 week. CPC-1, CPC-2, and hydroxyapatite cement elicited a moderate to intense inflammatory reaction at 7 days which decreased over time. CPC-1 and CPC-2 show promise for orthopedic applications.


2009 ◽  
Vol 29 (3) ◽  
pp. 969-975 ◽  
Author(s):  
Xia Li ◽  
Yu Sogo ◽  
Atsuo Ito ◽  
Hirotaka Mutsuzaki ◽  
Naoyuki Ochiai ◽  
...  

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