Potential Application of Protamine for Antimicrobial Biomaterials in Bone Tissue Engineering

Abstract

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−1 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−1) had both antimicrobial activity and biocompatibility and can be applied for bone substitutes in orthopedic fields.

Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?

“…Currently, the development of new antimicrobial peptides (AMPs) is an important area for bioengineering and biomedical applications [1][2][3]. AMPs are created as molecules that selectively affect the basic bacterial functions or growth processes of pathogenic organisms.…”

Antimicrobial peptides for bone tissue engineering: Diversity, effects and applications

“…Delivery of AMPs with nanoparticles has also gradually become a research hotspot to assist in the repair of infected bone defects. Commonly used nanoparticles for drug delivery system include polymeric microspheres and inorganic particles ( He et al, 2018a ; He et al, 2020 ; Honda et al, 2020 ). Honda et al noticed that the amine group of fish sperm protein arginine adsorbed with the phosphate group and hydroxyl group of HAp through electrostatic interactions, so they loaded fish sperm protein onto HAp by intermittent adsorption and compressed it into bone implants ( Honda et al, 2020 ).…”

“…Commonly used nanoparticles for drug delivery system include polymeric microspheres and inorganic particles ( He et al, 2018a ; He et al, 2020 ; Honda et al, 2020 ). Honda et al noticed that the amine group of fish sperm protein arginine adsorbed with the phosphate group and hydroxyl group of HAp through electrostatic interactions, so they loaded fish sperm protein onto HAp by intermittent adsorption and compressed it into bone implants ( Honda et al, 2020 ). It has the osteogenic properties expected of a bone scaffold and the antimicrobial activity conferred by AMPs.…”

“…It has the osteogenic properties expected of a bone scaffold and the antimicrobial activity conferred by AMPs. In addition, this team found that HAp-adsorbed fisetin is released by ion exchange, so the salt concentration in the local environment can modulate the release of AMPs from the nanoparticles ( Honda et al, 2020 ). Another team used negatively charged filamentous protein particles (SFNPs) to adsorb positively charged LL37 and crosslink it to the surface of the titanium scaffold ( He et al, 2019 ).…”

Recent Advances in the Treatment of Bone Metastases and Primary Bone Tumors: An Up-to-Date Review

“…To improve the inherent properties of the base material, bone scaffold surfaces can also be functionalized through several methods, such as coatings and immobilized molecules [3,16,186] (Figure 6).…”