Sustained Release of Antimicrobial Peptide from Self-Assembling Hydrogel Enhanced Osteogenesis

J Biomater Sci Polym Ed. 2018 Oct;29(15):1812-1824. doi: 10.1080/09205063.2018.1504191. Epub 2018 Sep 29.

Abstract

Biomaterials have been widely used in bone infection and osteomyelitis resulting from their versatile functionalities. As far as we know, the appearance of osteomyelitis was mainly caused by bacteria. Therefore, a biomaterial that can cure bone infection and promote osteogenesis may become an ideal candidate for the treatment of osteomyelitis. Cationic antimicrobial peptides (AMPs) have been proved to have an excellent ability to kill bacteria, fungi, viruses, and parasites. However, the application of AMPs in bone infection and osteomyelitis is quite limited. Here, we designed a new hydrogel that has an inhibitory effect on the proliferation of S. aureus and enhances osteogenesis. RADA16 self-assembling peptide has been applied for AMPs delivery. In this study, we demonstrated that RADA16 could form a stable structure and afford the sustained release of AMPs. The interwoven nanofiber morphology was detected by field emission scanning electron microscopy. The sustained release study revealed that the release of AMPs could be obtained until 28 days. In vitro research showed this new self-assembling hydrogel could promote the proliferation of bone mesenchymal stem cells (BMSCs) and inhibited the growth of S. aureus. More importantly, the results in vivo also proved that RADA16-AMP self-assembling peptide had an excellent effect on bone formation. Our findings implied that we successfully combined RADA16 and AMPs together and laid the foundation for the application of this new hydrogel and open new avenues for biomaterials.

Keywords: Osteomyelitis; RADA16; antibiosis; bone marrow mesenchymal stem cell; cationic antimicrobial peptides; osteogenesis; self-assembling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Antimicrobial Cationic Peptides / chemistry*
  • Antimicrobial Cationic Peptides / pharmacology
  • Biocompatible Materials / chemistry
  • Bone and Bones / cytology
  • Cell Proliferation / drug effects
  • Delayed-Action Preparations
  • Dimerization
  • Drug Liberation
  • Hydrogels / chemistry*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Nanofibers / chemistry
  • Osteogenesis / drug effects*
  • Rabbits
  • Staphylococcus aureus / drug effects

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Biocompatible Materials
  • Delayed-Action Preparations
  • Hydrogels