# Effects of antibiotics encapsulated in hyaluronic acid hydrogels on different osteogenic cells and bacteria

## TL;DR

A hyaluronic acid hydrogel loaded with antibiotics does not harm bone cells and can inhibit bacteria, making it a potential treatment for orthopedic implant infections.

## Contribution

A novel antibiotic-loaded hyaluronic acid hydrogel was tested for toxicity on osteogenic cells and antibacterial efficacy against staphylococci.

## Key findings

- Antibiotic-loaded hydrogels did not harm human and mouse osteoblasts at clinically relevant concentrations.
- Cefuroxime-loaded hydrogels inhibited Staphylococcus aureus growth but not Staphylococcus epidermidis.
- Vancomycin was released more slowly than cefuroxime from the hydrogel.

## Abstract

Topical application of antibiotics in the treatment of orthopaedic implant-related infections can be achieved by using hyaluronic acid (HA)-based hydrogels as carriers. Our aim was to investigate potential toxic effects of a novel antibiotic-loaded hydrogel on osteogenic cells and its antibacterial effect against staphylococci. A covalently cross-linked hyaluronic acid (HA)-based hydrogel was loaded with increasing concentrations of cefuroxime and vancomycin and their release was examined by UV spectrometry. Primary human (HoBs), mouse (MoBs) osteoblasts, or SaoS-2 cells were either exposed to the drug-loaded hydrogel or to antibiotics alone, followed by assessment of cell metabolism and proliferation. Antibacterial effects were evaluated against Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis). Increasing concentrations of antibiotics did not affect cell metabolism in any osteogenic cell type, whereas cell proliferation remained unaltered in MoBs, was significantly reduced in SaoS-2, and was stimulated in HoBs. Cultures of MoBs and HoBs tolerated higher concentrations of vancomycin than SaoS-2. Antibiotic-loaded hydrogels did not exert toxic effects on HoBs. After 24 h, 16.8% of vancomycin and 70.8% of cefuroxime were released from the hydrogel. Cefuroxime-loaded hydrogels significantly inhibited growth of S. aureus but not of S. epidermidis, while vancomycin-loaded hydrogel had scarce effects on S. epidermidis. Loading HA-based hydrogel with antibiotics does not harm osteoblasts at clinically relevant concentrations but inhibits bacterial growth. Higher loading of vancomycin may be required due to its slow release while cefuroxime is released more rapidly. A resorbable, antibiotic-loaded hydrogel may be used for implant-related infections in orthopaedics.