Potential Application of Protamine for Antimicrobial Biomaterials in Bone Tissue Engineering

• Published in: International journal of molecular sciences Vol. 21; no. 12; p. 4368
• Main Authors: Honda, Michiyo, Matsumoto, Morio, Aizawa, Mamoru
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19-06-2020; MDPI
• Subjects: Adsorption; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antibacterial agents; Antibiotics; Antimicrobial activity; Antimicrobial agents; antimicrobial peptide; Antimicrobial peptides; Bacteria; Bacteria - drug effects; Bacteria - growth & development; Bacterial Adhesion - drug effects; Bactericidal activity; Biocompatibility; biofilm formation; Biofilms; Biofilms - drug effects; Biomedical materials; Bone and Bones - drug effects; Bone and Bones - physiology; Bone biomaterials; Bone Substitutes - chemistry; Bone Substitutes - pharmacology; Bones; Cell division; Cell Line; Cytotoxicity; Disintegration; Dosage; Drug resistance; Durapatite - chemistry; E coli; Electrostatic properties; Gram-positive bacteria; Humans; Hydrophobicity; Hydroxyapatite; implant-related infection; Materials Testing; Medical equipment; Microbial Viability - drug effects; Morphology; Orthopedics; Osteoblasts - cytology; Osteoblasts - drug effects; Peptides; Plankton - drug effects; Plankton - growth & development; protamine; Protamine sulfate; Protamines - chemistry; Protamines - pharmacology; Proteins; Spectrum analysis; Staphylococcus infections; Substitute bone; Surgical implants; Tissue Engineering; Transplants & implants; hydroxyapatite; biofilm formation; protamine; antimicrobial peptide; implant-related infection
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21124368

Bacterial infection of biomaterials is a serious problem in the field of medical devices. It is urgently necessary to develop new biomaterials with bactericidal activity. Antimicrobial peptides and proteins (AMPs), alternative antibacterial agents, are expected to overcome the bacterial resistance. The aim of this study was to develop a new intelligent material in bone tissue engineering based on protamine-loaded hydroxyapatite (protamine/HAp) that uses AMPs rather than antibiotics. It was found that the adsorption of protamine to HAp followed the Langmuir adsorption model and was due to electrostatic and/or hydrophobic interactions. In vitro bacterial adhesion and growth on protamine/HAp was inhibited in a protamine dose-dependent manner. Adherent bacteria exhibited an aberrant morphology for high dosages of protamine/HAp, resulting in the formation of large aggregates and disintegration of the membrane. The released protamine from protamine/HAp also prevented the growth of planktonic bacteria in vitro. However, a high dosage of protamine from powders at loading concentrations over 1000 μg·mL
induced a cytotoxic effect in vitro, although those exhibited no apparent cytotoxicity in vivo. These data revealed that protamine/HAp (less than 1000 μg·mL
) had both antimicrobial activity and biocompatibility and can be applied for bone substitutes in orthopedic fields.