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      Treatment of Staphylococcus aureus-induced chronic osteomyelitis with bone-like hydroxyapatite/poly amino acid loaded with rifapentine microspheres

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          The purpose of this study was to investigate the curative effect of bone-like hydroxyapatite/poly amino acid (BHA/PAA) as a carrier for poly(lactic-co-glycolic acid)-coated rifapentine microsphere (RPM) in the treatment of rabbit chronic osteomyelitis induced by Staphylococcus aureus.


          RPM was prepared through an oil-in-water emulsion solvent evaporation method, and RPM was combined with BHA/PAA to obtain drug-loaded, slow-releasing materials. Twenty-six New Zealand white rabbits were induced to establish the animal model of chronic osteomyelitis. After debridement, the animals were randomly divided into three groups (n=8): the experimental group (with RPM-loaded BHA/PAA), the control group (with BHA/PAA), and the blank group. The RPM-loaded BHA/PAA was evaluated for antibacterial activity, dynamics of drug release, and osteogenic ability through in vitro and in vivo experiments.


          In vitro, RPM-loaded BHA/PAA released the antibiotics slowly, inhibiting the bacterial growth of S. aureus for up to 5 weeks. In vivo, at week 4, the bacterial colony count was significantly lower in the experimental group than in the control and blank groups ( P<0.01). At week 12, the chronic osteomyelitis was cured and the bone defect was repaired in the experimental group, whereas the infection and bone defect persisted in the control and blank groups.


          In vitro and in vivo experiments demonstrated that RPM-loaded BHA/PAA effectively cured S. aureus-induced chronic osteomyelitis. Therefore, BHA/PAA has potential value as a slow-releasing material in clinical setting. Further investigation is needed to determine the optimal dosage for loading rifapentine.

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          Most cited references 29

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          Bone and joint infections are painful for patients and frustrating for both them and their doctors. The high success rates of antimicrobial therapy in most infectious diseases have not yet been achieved in bone and joint infections owing to the physiological and anatomical characteristics of bone. The key to successful management is early diagnosis, including bone sampling for microbiological and pathological examination to allow targeted and long-lasting antimicrobial therapy. The various types of osteomyelitis require differing medical and surgical therapeutic strategies. These types include, in order of decreasing frequency: osteomyelitis secondary to a contiguous focus of infection (after trauma, surgery, or insertion of a joint prosthesis); that secondary to vascular insufficiency (in diabetic foot infections); or that of haematogenous origin. Chronic osteomyelitis is associated with avascular necrosis of bone and formation of sequestrum (dead bone), and surgical debridement is necessary for cure in addition to antibiotic therapy. By contrast, acute osteomyelitis can respond to antibiotics alone. Generally, a multidisciplinary approach is required for success, involving expertise in orthopaedic surgery, infectious diseases, and plastic surgery, as well as vascular surgery, particularly for complex cases with soft-tissue loss.
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            Role of scaffold internal structure on in vivo bone formation in macroporous calcium phosphate bioceramics.

            Purpose of this study was the analysis of the role of density and pore interconnection pathway in scaffolds to be used as bone substitutes. We have considered 2 hydroxyapatite bioceramics with identical microstructure and different macro-porosity, pore size distribution and pore interconnection pathway. The scaffolds were obtained with two different procedures: (a) sponge matrix embedding (scaffold A), and (b) foaming (scaffold B). Bone ingrowth within the two bioceramics was obtained using an established model of in vivo bone formation by exogenously added osteoprogenitor cells. The histological analysis of specimens at different time after in vivo implantation revealed in both materials a significant extent of bone matrix deposition. Interestingly enough, scaffold B allowed a faster occurrence of bone tissue, reaching a steady state as soon as 4 weeks. Scaffold A on the other hand reached a comparable level of bone formation only after 8 weeks of in vivo implantation. Both scaffolds were well vascularised, but larger blood vessels were observed in scaffold A. Here we show that porosity and pore interconnection of osteoconductive scaffolds can influence the overall amount of bone deposition, the pattern of blood vessels invasion and finally the kinetics of the bone neoformation process.
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              Biofilm theory can guide the treatment of device-related orthopaedic infections.

               J Costerton (2005)
              Direct observations of the surfaces of orthopaedic prostheses that have failed and of bone affected by osteomyelitis with and without the presence of a prosthesis have shown that the bacteria that cause these infections live in well-developed biofilms. The cells within these matrix-enclosed surface-associated communities are protected from host defenses and antibiotics, and clinical experience has shown that they must be removed physically before the infection can be resolved. The biofilm etiology of these diseases demands new diagnostic methods because biofilm cells typically do not grow on agar plates when recovered by scraping or swabbing. I will recommend new molecular and immunologic diagnostic methods that have been useful in other biofilm infections. These diseases progress through quiescent periods that alternate with acute exacerbations, and clinicians must realize that antibiotic therapy can control the acute phases but cannot resolve the basic biofilm nidus of the infection. Now that it has been realized that these orthopaedic infections are caused by relatively common biofilm-forming bacterial pathogens, new technologies that deliver very high concentrations of antibiotics locally and "on demand" and novel molecular "mimics" that block the signals that control biofilm formation need to be examined.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                20 July 2015
                : 9
                : 3665-3676
                [1 ]Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, People’s Republic of China
                [2 ]Department of Orthopaedic Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
                [3 ]Pediatric Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
                [4 ]Department of Cardiology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
                [5 ]Department of Radiology, College of Basic Medicine, Chongqing Medical University, Chongqing, People’s Republic of China
                Author notes
                Correspondence: Yong-Fen Yi, Department of Pathology, College of Basic Medicine, Chongqing Medical University, No. 1 Xueyuan Road, Yuzhong District, Chongqing 400016, People’s Republic of China, Tel +86 13 7083 10802, Fax +86 23 6848 5540, Email yiyongfen1953@ 123456aliyun.com
                © 2015 Yan et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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