(194q) Engineering an Adhesive and Antimicrobial Nanocomposite Hydrogel for Wound Healing Applications

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 wound care management to fabricate hydrogels which possesses adequate adhesiveness, strong antimicrobial properties, and excellent mechanical properties. Wound infection is a serious problem, and can be dire for people with compromised immune systems, diabetes or other conditions – or just for people who leave an infected wound alone for too long. Therefore, designing adhesive hydrogels with desired antibacterial activity and sufficient adhesion and mechanical properties is of particular importance for advancement of infected wound healing process. To address these limitations, we engineered an antimicrobial nanocomposite adhesive by incorporating Zinc-Oxide tetrapods (ZnO-T)¹ 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 for a few seconds.

Materials and Methods:

The nanocomposite hydrogels were engineered by dispersing various concentrations of ZnO-T in the range of 0 to 2 %(w/w) 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 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 incorporated with commercially available ZnO spherical (ZnO-C) nanoparticles. For the in vitro study, we characterized the growth, viability and proliferation of encapsulated 3T3 fibroblast cells within the hydrogel using Prestoblue, Live/Dead, and Actin/DAPI assays², respectively. In addition, we exposed the engineered nanocomposites to both gram-positive and gram-negative bacteria (Escherichia coli (E.Coli) and Pseudomonas aeruginosa (P.a) bacteria) to evaluate their antimicrobial properties.

Results:

Our results showed that incorporating ZnO particles with different-shape particles significantly influenced the physicochemical and antimicrobial activities of the resultant composite hydrogels. We demonstrated that the nanocomposite hydrogels loaded with ZnO-T had significantly higher tensile and compressive properties 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 ZnO-T the distance between tetrapod arms can prevent aggregation of nanoparticles in solution 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. These nanocomposite hydrogels also exhibited favourable biological characteristics by supporting the growth, spreading and proliferation of 3D encapsulated 3T3 fibroblast cells inside the engineered hydrogels. 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 offered higher antibacterial activity as compared to Kanamycin (commercial antibiotic) as well as control samples containing ZnO-C.

Conclusion:

Our results demonstrate that the engineered nanocomposite adhesive hydrogels have potential to be used for wound healing as well as various surgical procedures that prone to risk of infection.

References:

[1] Mishra, Yogendra Kumar, and Rainer Adelung. "ZnO tetrapod materials for functional applications." Materials Today (2017).

[2] Annabi N, Mithieux SM, Zorlutuna P, Camci-Unal G, Weiss AS, Khademhosseini A. “Engineered cell-laden human protein-based elastomer”. Biomaterials. 2013;34(22):5496-505.

Acknowledgments:

This work was supported by the National Institutes of Health (NIH) under award number [1R01EB023052; 1R01HL140618]