Dual-Functional Implant Based on Gellan-Xanthan Hydrogel with Diopside, BMP-2 and Lysostaphin for Bone Defect Repair and Control of Staphylococcal Infection

Macromol Biosci. 2024 Nov;24(11):e2400205. doi: 10.1002/mabi.202400205. Epub 2024 Aug 14.

Abstract

A new dual-functional implant based on gellan-xanthan hydrogel with calcium-magnesium silicate ceramic diopside and recombinant lysostaphin and bone morphogenetic protein 2 (BMP-2)-ray is developed. In this composite, BMP-2 is immobilized on microparticles of diopside while lysostaphin is mixed directly into the hydrogel, providing sustained release of BMP-2 to allow gradual bone formation and rapid release of lysostaphin to eliminate infection immediately after implantation. Introduction of diopside of up to 3% (w/v) has a negligible effect on the mechanical properties of the hydrogel but provides a high sorption capacity for BMP-2. The hydrogels show good biocompatibility and antibacterial activity. Lysostaphin released from the implants over a 3 h period efficiently kills planktonic cells and completely destroys 24 h pre-formed biofilms of Staphylococcus aureus. Furthermore, in vivo experiments in a mouse model of critically-sized cranial defects infected with S. aureus show a complete lack of osteogenesis when implants contain only BMP-2, whereas, in the presence of lysostaphin, complete closure of the defect with newly formed mineralized bone tissue is observed. Thus, the new implantable gellan-xanthan hydrogel with diopside and recombinant lysostaphin and BMP-2 shows both osteogenic and antibacterial properties and represents a promising material for the treatment and/or prevention of osteomyelitis after bone trauma.

Keywords: BMP‐2; Staphylococcus aureus; diopside; gellan‐xanthan hydrogel; implant; lysostaphin; osteogenesis.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Biofilms / drug effects
  • Bone Morphogenetic Protein 2* / chemistry
  • Bone Morphogenetic Protein 2* / pharmacology
  • Bone Regeneration / drug effects
  • Humans
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Lysostaphin* / chemistry
  • Lysostaphin* / pharmacology
  • Mice
  • Osteogenesis / drug effects
  • Polysaccharides, Bacterial* / chemistry
  • Polysaccharides, Bacterial* / pharmacology
  • Staphylococcal Infections* / drug therapy
  • Staphylococcus aureus* / drug effects

Substances

  • Bone Morphogenetic Protein 2
  • gellan gum
  • Polysaccharides, Bacterial
  • Hydrogels
  • Lysostaphin
  • xanthan gum
  • Anti-Bacterial Agents