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

• Published in: Macromolecular bioscience 2024-11, Vol.24 (11), p.e2400205-n/a
• Main Authors: Karyagina, Anna S., Grishin, Alexander V., Kudinova, Alina G., Bulygina, Inna N., Koudan, Elizaveta V., Orlova, Polina A., Datsenko, Vera P., Zhulina, Anna V., Grunina, Tatyana M., Poponova, Maria S., Krivozubov, Mikhail S., Gromova, Maria S., Strukova, Natalia V., Generalova, Maria S., Nikitin, Kirill E., Shchetinin, Igor V., Luchnikov, Lev O., Zaitseva, Svetlana V., Kirsanova, Maria A., Statnik, Eugene S., Senatov, Fedor S., Lunin, Vladimir G., Gromov, Alexander V.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Biocompatibility; Biofilms; Biofilms - drug effects; BMP‐2; Bone growth; Bone implants; Bone morphogenetic protein 2; Bone Morphogenetic Protein 2 - chemistry; Bone Morphogenetic Protein 2 - pharmacology; Bone morphogenetic proteins; Bone Regeneration - drug effects; Calcium magnesium silicates; Controlled release; Defects; Diopside; Gellan gum; gellan‐xanthan hydrogel; Humans; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; implant; Lysostaphin; Lysostaphin - chemistry; Lysostaphin - pharmacology; Magnesium silicates; Mechanical properties; Mice; Microparticles; Osteogenesis; Osteogenesis - drug effects; Osteomyelitis; Planktonic cells; Polysaccharides, Bacterial - chemistry; Polysaccharides, Bacterial - pharmacology; Staphylococcal Infections - drug therapy; Staphylococcus aureus; Staphylococcus aureus - drug effects; Surgical implants; Sustained release; Transplants & implants; Xanthan
• ISSN: 1616-5187; 1616-5195; 1616-5195
• DOI: 10.1002/mabi.202400205

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. A gellan‐xanthan hydrogel with recombinant lysostaphin and BMP‐2 adsorbed on diopside microparticles with high biocompatibility, antistaphylococcal, and antibiofilm activity has been developed. In the presence of both proteins, but not BMP‐2 alone, pronounced osteogenesis is observed four weeks after implantation in a murine model of critically‐sized cranial defects accompanied by S. aureus infection.