Nanohydroxyapatite-Loaded, Self-Assembled Peptide Gels for Antibacterial and Osteogenic Activities

Bone constitutes the primary component of the skeletal system, and a substantial reduction in bone density can occur due to trauma, aging, infections, and illnesses. Infections often hinder bone regeneration, with S. aureus being the most frequently encountered bacterium in such infections. Peptide-based self-assembled materials have attracted significant interest in the field of biomaterials because of their biomimetic properties, minimal immunogenicity, and ease of production, and peptides, ranging from short to ultrashort length, have been demonstrated to undergo supramolecular self-assembly to form nanofibrous architectures with varying morphology and mechanical strength. Ultrashort peptide gels containing positively charged amino acids have demonstrated potent antibacterial properties and possess the ability to mimic the extracellular matrix (ECM). Peptide-based bone regeneration scaffolds incorporating antibiotics have been investigated over the years, but they suffer from erratic antibiotic release from scaffolds and the development of antimicrobial resistance in bacteria. Inspired by the natural ECM of bone, where nanohydroxyapatite (HAp) crystals adhere to collagen fibers and provide strength and support for the growth and differentiation of bone cells, we have developed nanofibrous hydroxyapatite-loaded antibacterial tripeptide gels having osteogenic differentiation potential. The nanofibrous peptide gels entrapping HAp nanoparticles were visualized using FE-SEM and AFM. The gels showed good viscoelastic properties, with mechanical strengths in the range of 1.3 to 12.3 kPa and showed potent antibacterial activity (>85%) against S. aureus. The gels were cytocompatible and supported the growth, migration, and differentiation of osteoblast precursor MC3T3-E1 cells. This antibiotic-/growth factor-free approach addresses the constraints associated with the conventional antibacterial bone regeneration scaffolds while showing excellent osteogenic and antibacterial activities. The antibacterial peptide gels reported in this work show promise as bionanomaterial-based bone regeneration scaffolds for treating infected bone defects.