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Author Notes:

Andrés J. García, Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA 30332-0363, USA. Email: andres.garcia@me.gatech.edu

The pSEVAplexA plasmid was kindly provided by Victor de Lorenzo. The Pseudomonas bacteriophage used in this study was kindly provided by Rodney Donlan. Transfection of the pSEVAplexA plasmid into PsAer-9 was performed by Nina Dinjaski and Auxiliadora Prieto. We thank the core facilities at the Parker H. Petit Institute for Bioengineering and Bioscience at the Georgia Institute of Technology for the use of their shared equipment, services and expertise. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R01AR062920 (A.J.G.) and F30AR069472 (C.T.J.). J.A.W. acknowledges support under the Georgia Tech President’s Undergraduate Research Award (PURA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Subject:

Research Funding:

National Institutes of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, Grant/Award Numbers: F30AR069472, R01AR062920; The Georgia Tech President’s Undergraduate Research Award (PURA)

Keywords:

  • bacteriophage
  • biofilm
  • hydrogel
  • orthopedic
  • Pseudomonas

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

Tools:

Journal Title:

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A

Volume:

Volume 108, Number 1

Publisher:

, Pages 39-49

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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.
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