New antibacterial microporous CaP materials loaded with phages for prophylactic treatment in bone surgery

Meurice, Edwige; Rguiti, Emmanuelle; Brutel, Annie; Hornez, Jean‐Christophe; Leriche, Anne; Descamps, M.; Bouchart, Franck

doi:10.1007/s10856-012-4711-6

Cited by 22 publications

(23 citation statements)

References 25 publications

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“…10,12,17 Several studies have explored the potential of systemic phages administration for the treatment of implant-related infections. [13][14][15][18][19][20][21] Nonetheless, experimental studies using phages-loaded biomaterials for local delivery approaches are scarce, 9,22,23 focusing on the phages release and antimicrobial activity, without simultaneously exploring the potential combination with a regeneration inductive biomaterial. Therefore, this work aims to develop a multi-functional regenerative biomaterial for local phage delivery, based on an alginate-nanohydroxyapatite (Alg-nanoHA) hydrogel system.…”

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confidence: 99%

Encapsulated bacteriophages in alginate-nanohydroxyapatite hydrogel as a novel delivery system to prevent orthopedic implant-associated infections

Barros

Melo

Silva

et al. 2020

Nanomedicine: Nanotechnology, Biology and Medicine

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An innovative delivery system based on bacteriophages-loaded alginate-nanohydroxyapatite hydrogel was developed as a multifunctional approach for local tissue regeneration and infection prevention and control. Bacteriophages were efficiently encapsulated, without jeopardizing phage viability and functionality, nor affecting hydrogel morphology and chemical composition. Bacteriophage delivery occurred by swelling-disintegration-degradation process of the alginate structure and was influenced by environmental pH. Good tissue response was observed following the implantation of bacteriophages-loaded hydrogels, sustaining their biosafety profile. Bacteriophagesloaded hydrogels did not affect osteoblastic cells' proliferation and morphology. A strong osteogenic and mineralization response was promoted through the implantation of hydrogels system with nanohydroxyapatite. Lastly, bacteriophages-loaded hydrogel showed excellent antimicrobial activity inhibiting the attachment and colonization of multidrug-resistant E. faecalis surrounding and within femoral tissues. This new local delivery approach could be a promising approach to prevent and control bacterial contamination during implantation and bone integration.

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confidence: 99%

Encapsulated bacteriophages in alginate-nanohydroxyapatite hydrogel as a novel delivery system to prevent orthopedic implant-associated infections

Barros

Melo

Silva

et al. 2020

Nanomedicine: Nanotechnology, Biology and Medicine

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“…Most common strains of bacteria implicated in orthopedic implant‐associated infections have identified bacteriophage (Campoccia et al, ; Wittebole et al, ), making the approach used to prevent P. aeruginosa colonization in this study generalizable to a broad spectrum of organisms involved in clinical bone infections and osteomyelitis. Indeed, recent research has explored the use of bacteriophage to treat bone infections (Kaur, Harjai, & Chhibber, , ; Kishor et al, ; Meurice et al, ; Nir‐Paz et al, ; Yilmaz et al, ). Future studies could investigate the delivery of multiple bacteriophage targeting different genera such a Staphylococcus and Enterococcus , and explore their ability to combat the complex, multispecies biofilms often found in clinical osteomyelitis cases (Bryers, ).…”

Section: Discussionmentioning

confidence: 99%

Bacteriophage delivering hydrogels reduce biofilm formation in vitro and infection in vivo

Wroe

Johnson

Garcı́a

2019

J Biomedical Materials Res

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Implanted orthopedic devices become infected more frequently than any other implanted surgical device. These infections can be extremely costly and result in significant patient morbidity. Current treatment options typically involve the long term, systemic administration of a combination of antibiotics, often followed by implant removal. Here we engineered an injectable hydrogel capable of encapsulating Pseudomonas aeruginosa bacteriophage and delivering active phage to the site of bone infections. Bacteriophage retain their bacteriolytic activity after encapsulation and release from the hydrogel, and their rate of release from the hydrogel can be controlled by gel formulation. Bacteriophage-encapsulating hydrogels effectively kill their host bacteria in both planktonic and biofilm phenotypes in vitro without influencing the metabolic activity of human mesenchymal stromal cells. Bacteriophage-encapsulating hydrogels were used to treat murine radial segmental defects infected with P. aeruginosa. The hydrogels achieved a 4.7-fold reduction in live P. aeruginosa counts at the infection site compared to bacteriophage-free hydrogels at 7 days postimplantation. These results support the development of bacteriophage-delivering hydrogels to treat local bone infections. K E Y W O R D S bacteriophage, biofilm, hydrogel, orthopedic, Pseudomonas

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“…Which strategy is used is generally dictated by the type of biomaterial and its processability. For example, ceramics such as hydroxyapatite (HAP) or other calcium phosphates (CAP) require such high sintering temperatures (Meurice et al, 2012) that surface adsorption after sintering is the only viable method for direct phage loading for these materials. Other manufacturing processes such as organic solvent emulsions, electro-spinning/spraying or chemical modifications of biomaterials require conditions that could be harsh for the relatively fragile bacteriophages.…”

Section: Considerations In Manufacturing Bacteriophage Loaded Biomatementioning

confidence: 99%

“…Examples of inorganic materials include ceramics, metals and salts. Although not as frequently investigated as organic phage carriers, delivery of bacteriophages using inorganic materials has received some attention, especially in the field of orthopedic infections (Meurice et al, 2012;Hornez et al, 2013). Literature regarding inorganic phage carriers can be found in Table 4.…”

Section: Inorganic Materialsmentioning

confidence: 99%

Local Bacteriophage Delivery for Treatment and Prevention of Bacterial Infections

et al. 2020

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As viruses with high specificity for their bacterial hosts, bacteriophages (phages) are an attractive means to eradicate bacteria, and their potential has been recognized by a broad range of industries. Against a background of increasing rates of antibiotic resistance in pathogenic bacteria, bacteriophages have received much attention as a possible "last-resort" strategy to treat infections. The use of bacteriophages in human patients is limited by their sensitivity to acidic pH, enzymatic attack and short serum half-life. Loading phage within a biomaterial can shield the incorporated phage against many of these harmful environmental factors, and in addition, provide controlled release for prolonged therapeutic activity. In this review, we assess the different classes of biomaterials (i.e., biopolymers, synthetic polymers, and ceramics) that have been used for phage delivery and describe the processing methodologies that are compatible with phage embedding or encapsulation. We also elaborate on the clinical or preclinical data generated using these materials. While a primary focus is placed on the application of phage-loaded materials for treatment of infection, we also include studies from other translatable fields such as food preservation and animal husbandry. Finally, we summarize trends in the literature and identify current barriers that currently prevent clinical application of phage-loaded biomaterials.

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New antibacterial microporous CaP materials loaded with phages for prophylactic treatment in bone surgery

Cited by 22 publications

References 25 publications

Encapsulated bacteriophages in alginate-nanohydroxyapatite hydrogel as a novel delivery system to prevent orthopedic implant-associated infections

Encapsulated bacteriophages in alginate-nanohydroxyapatite hydrogel as a novel delivery system to prevent orthopedic implant-associated infections

Bacteriophage delivering hydrogels reduce biofilm formation in vitro and infection in vivo

Local Bacteriophage Delivery for Treatment and Prevention of Bacterial Infections

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