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
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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