Engineering an adhesive and antimicrobial nanocomposite hydrogel

Abstract

Hydrogel-based adhesives become very popular nowadays for various surgical and tissue engineering applications due to their biocompatibility and biomimetic properties. However, there are always major challenges persist in fabricating hydrogels which possesses adequate tissue adhesiveness, strong antimicrobial properties, and excellent mechanical properties. An estimated 700,000 people die yearly around the world because they have an infection that has become resistance to the antibiotics and drugs used to treat it. Therefore, designing adhesive hydrogels with desired antibacterial activity, sufficient adhesion and mechanical properties is of importance for many tissue engineering applications. To address these limitations, we engineered an antimicrobial nanocomposite adhesive by incorporating Zinc-Oxide tetrapods (ZnO-T) in a photocrosslinkable hydrogel prepolymer solution which can be topically applied on wound site by spraying and easily crosslinked to form an adhesive hydrogel by UV irradiation in a few seconds. These nanocomposite hydrogels were engineered by dispersing various concentrations of ZnO-T in the range of 0 to 2 %(w/v) in gelatin methacryloyl (GelMA) prepolymer solution with different concentrations ranging from 5 to 20%(w/v). Then, the physical properties of the nanocomposite hydrogels were evaluated by measuring the elastic and compressive modulus, elasticity, swellability and degradation. Moreover, we determined various tissue adhesive properties of hydrogel based on various standard adhesion tests such as wound closure, lap shear and burst pressure. We also compared these properties with the hydrogels loaded with commercially available ZnO spherical (ZnO-C) nanoparticles. In addition, we exposed the engineered nanocomposites to (Escherichia coli (E.Coli) and Pseudomonas aeruginosa (P.a) bacteria) to evaluate their antimicrobial properties. We demonstrated that the nanocomposite hydrogels loaded with ZnO-T had significantly higher tensile and compressive strength as compared to hydrogel containing ZnO-C. This could be due to the aggregation of ZnO-C, particularly at higher concentration which can adversely affect mechanical properties whereas in case of ZnO-T, the distance between tetrapod arms can prevent aggregation of nanoparticles in solution and resulting in improved mechanical properties. In addition, adhesion tests revealed significantly higher tissue adhesion for ZnO-T loaded hydrogel as compared to ZnO-C incorporated nanocomposite. This can be due to the shape of ZnO-T, which may facilitate mechanical interlocking with the native tissues. Antimicrobial results showed that not only the zone of inhibition increased by increasing the concentration of the both types of ZnO nanoparticles from 0 to 2%(w/w), hydrogels loaded with ZnO-T also offered higher antibacterial activity as compared to Kanamycin (commercial antibiotic) as well as control samples containing ZnO-C. Our results demonstrate that the engineered nanocomposite adhesive hydrogels have potential to be used for various surgical procedures that prone to risk of infection--Author's abstract