Lysostaphin and BMP-2 co-delivery reduces S. aureus infection and regenerates critical-sized segmental bone defects
Autor: | Edward A. Botchwey, Karen E. Martin, Christopher T. Johnson, Mary Caitlin P. Sok, Andrés J. García, Pranav P. Kalelkar, Jeremy D. Caplin |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Male
Staphylococcus aureus Bone Regeneration medicine.medical_treatment Bone Morphogenetic Protein 2 02 engineering and technology medicine.disease_cause Bone morphogenetic protein 2 complex mixtures Microbiology 03 medical and health sciences Mice Immune system Engineering Drug Delivery Systems Transforming Growth Factor beta Medicine Animals Orthopedic Procedures Pathogen Research Articles 030304 developmental biology Inflammation 0303 health sciences Multidisciplinary Lysostaphin business.industry Biofilm technology industry and agriculture SciAdv r-articles Hydrogels Prostheses and Implants Staphylococcal Infections 021001 nanoscience & nanotechnology Recombinant Proteins 3. Good health Anti-Bacterial Agents Mice Inbred C57BL Cytokine Applied Sciences and Engineering Self-healing hydrogels 0210 nano-technology business Research Article |
Zdroj: | Science Advances |
ISSN: | 2375-2548 |
Popis: | Use of BMP-2 and lysostaphin-loaded hydrogels simultaneously clears S. aureus infection and repairs bone defects. Staphylococcus aureus is the most common pathogen associated with bacterial infections in orthopedic procedures. Infections often lead to implant failure and subsequent removal, motivating the development of bifunctional materials that both promote repair and prevent failure due to infection. Lysostaphin is an anti-staphylococcal enzyme resulting in bacterial lysis and biofilm reduction. Lysostaphin use is limited by the lack of effective delivery methods to provide sustained, high doses of enzyme to infection sites. We engineered a BMP-2–loaded lysostaphin-delivering hydrogel that simultaneously prevents S. aureus infection and repairs nonhealing segmental bone defects in the murine radius. Lysostaphin-delivering hydrogels eradicated S. aureus infection and resulted in mechanically competent bone. Cytokine and immune cell profiling demonstrated that lysostaphin-delivering hydrogels restored the local inflammatory environment to that of a sterile injury. These results show that BMP-2–loaded lysostaphin-delivering hydrogel therapy effectively eliminates S. aureus infection while simultaneously regenerating functional bone resulting in defect healing. |
Databáze: | OpenAIRE |
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