Non-leaching, Highly Biocompatible Nanocellulose Surfaces That Efficiently Resist Fouling by Bacteria in an Artificial Dermis Model.

Ghada Hassan,Monika Österberg,Ralf Zimmermann,Nina Forsman,Michael Chrubasik,Carsten Werner,Vânia M Moreira,Declan C Mullen,Xing Wan,Blair F Johnston,Leena Keurulainen,Luis M Bimbo,Leena-Sisko Johansson,Susanne Stehl,Tom Coenye,Per E J Saris,Frits Van Charante,Jari Yli-Kauhaluoma,Aruna S Prakash

doi:10.1021/acsabm.0c00203

Abstract

Bacterial biofilm infections incur massive costs on healthcare systems worldwide. Particularly worrisome are the infections associated with pressure ulcers and prosthetic, plastic, and reconstructive surgeries, where staphylococci are the major biofilm-forming pathogens. Non-leaching antimicrobial surfaces offer great promise for the design of bioactive coatings to be used in medical devices. However, the vast majority are cationic, which brings about undesirable toxicity. To circumvent this issue, we have developed antimicrobial nanocellulose films by direct functionalization of the surface with dehydroabietic acid derivatives. Our conceptually unique design generates non-leaching anionic surfaces that reduce the number of viable staphylococci in suspension, including drug-resistant Staphylococcus aureus, by an impressive 4-5 log units, upon contact. Moreover, the films clearly prevent bacterial colonization of the surface in a model mimicking the physiological environment in chronic wounds. Their activity is not hampered by high protein content, and they nurture fibroblast growth at the surface without causing significant hemolysis. In this work, we have generated nanocellulose films with indisputable antimicrobial activity demonstrated using state-of-the-art models that best depict an "in vivo scenario". Our approach is to use fully renewable polymers and find suitable alternatives to silver and cationic antimicrobials.

Highlights

Bacterial attachment and subsequent biofilm formation significantly hinder surface performance in a plethora of circumstances including food packaging, sanitary and household materials, as well as military and medical items.[1−4] As a consequence, the colonization of surfaces by bacteria has been under intensive research aiming at finding guiding principles to efficiently manipulate bacteria−surface interactions for the benefit of humans.[5−9] From a health perspective, the most worrisome biofilm-based infections are those associated with implanted medical devices; chronic wounds; and prosthetic, plastic, and reconstructive surgeries.[10−13] Biofilms are difficult to treat once established as microorganisms in biofilms are inherently tolerant and resistant to antimicrobial therapies
We found that cellulose nanofibrils (CNFs)-carboxymethyl cellulose (CMC)-7b was only 10-fold less active against a mutant strain of the Gram-positive Lactococcus lactis (LAC471) devoid of the AcmA autolysin than against the original L. lactis LAC460 strain, suggesting that it is unlikely that release of autolysins from bacteria surfaces can be regarded as the sole mechanism of action of the films
For the first time, nonleaching, anionic, and biocompatible CNF films with the ability to resist colonization by bacteria that would lead to the undesirable establishment of a biofilm, when tested in a model that mimics the physiological conditions present in chronic wounds

Summary

■ INTRODUCTION

Bacterial attachment and subsequent biofilm formation significantly hinder surface performance in a plethora of circumstances including food packaging, sanitary and household materials, as well as military and medical items.[1−4] As a consequence, the colonization of surfaces by bacteria has been under intensive research aiming at finding guiding principles to efficiently manipulate bacteria−surface interactions for the benefit of humans.[5−9] From a health perspective, the most worrisome biofilm-based infections are those associated with implanted medical devices; chronic wounds (including pressure ulcers); and prosthetic, plastic, and reconstructive surgeries.[10−13] Biofilms are difficult to treat once established as microorganisms in biofilms are inherently tolerant and resistant to antimicrobial therapies. The tight electrostatic interactions that positively charged nanomaterials establish upon contact with the negatively charged functional groups at the surface of bacteria have been extensively exploited in the design of contact-active antibacterial surfaces, albeit the well-documented toxicity of polycationic compounds.[21−24] In contrast, anionic surfaces circumvent this toxicity issue because they fail to induce the strong membrane polarization that leads to cell lysis. A wound dressing based on wood-derived CNF (FibDex)[41] was launched in the European market, showing the potential of CNF for the design of medical devices for human use alongside with bacterial cellulose and carboxymethyl cellulose (CMC)

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES