Microneedles Against Resistant Infections: Innovative Wound Healing with Chitosan and Nanozymes

Treating infected burn wounds - especially those involving antibiotic-resistant bacteria - remains a major challenge in modern medicine. A research team has now introduced a groundbreaking solution: a hydrogel-based microneedle system that combines so-called “high-entropy nanozymes” with chitosan.

This novel technology not only combats resistant pathogens but also actively promotes wound healing—with a special focus on chitosan’s role as a key material.

High-Entropy Nanozymes & Microneedles – A Novel Combination

At the core of the innovation is a “nanozyme,” a nanostructured material with enzyme-like function. The specially designed high-entropy nanozymes consist of multiple metal oxides and exhibit strong antibacterial effects, even against multidrug-resistant pathogens. These active agents are embedded in a fine microneedle array made from hydrogel—which is precisely applied to the affected skin, comparable to acupuncture but completely painless.

Infobox:

What are antibiotic-resistant and multidrug-resistant bacteria?
Antibiotic-resistant bacteria are microbes that have evolved so that common antibiotics no longer work against them. Especially problematic are multidrug-resistant bacteria - they are resistant to several (sometimes nearly all) commonly used antibiotics simultaneously.
Such pathogens can turn even harmless infections dangerous because established therapies fail. The World Health Organization WHO classifies multidrug-resistant bacteria as one of the greatest global health threats.

How do resistant pathogens arise?
Common causes include:
- Excessive or improper use of antibiotics
- Use in animal farming
- Incomplete antibiotic therapies
- Poor hygiene in healthcare settings
Once bacteria become resistant, they can even transfer their "resistance genes" to other bacteria, which provides an evolutionary advantage that can spread rapidly.

Typical multidrug-resistant wound infection pathogens:
MRSA (Methicillin-resistant Staphylococcus aureus): colonizes skin/ wounds, causes severe infections, often in hospitals
Pseudomonas aeruginosa: often found in moist wounds (e.g., burns), resistant to many antibiotics
Acinetobacter baumannii: survives long on skin/ surfaces, common in wound and ventilator-associated infections
VRE (Vancomycin-resistant Enterococcus faecium): enters the body through wounds, difficult to treat

Why this matters:
These pathogens significantly delay wound healing. New strategies like chitosan-containing microneedle systems can help locally fight resistant bacteria - without relying on traditional antibiotics.

Chitosan – The Biological Building Block for Healing

A key role in this system is played by chitosan - a biocompatible, naturally degradable polysaccharide derived from the exoskeletons of crustaceans. Its properties make it ideal for medical use:
Antibacterial
Chitosan itself has antimicrobial effects and supports the action of the nanozymes.
Anti-inflammatory
It reduces local inflammation, promoting faster regeneration.
Promotes cell proliferation
Chitosan supports the formation of new skin cells - crucial for healing large wounds.
Hydrogel formation
Its gel-forming properties enable the production of soft, flexible microneedles with optimal drug delivery.
In short: Chitosan is not just a carrier material - it is an active part of the therapy.

Choosing the Right Chitosan

At the core of the hydrogel-based microneedle system, Carboxymethyl Chitosan (CMC) was used – a chitosan derivative with significantly improved water solubility and biocompatibility in neutral to slightly basic environments.

Why was CMC used instead of "regular" chitosan? CMC shows better solubility at pH 7–8, enables more homogeneous hydrogel blends, and exhibits strong hemostatic and anti-inflammatory properties – all of which support wound healing. Additionally, its ability to form flexible hydrogels makes it an ideal choice for microneedle applications.
Here’s an overview based on studies (e.g., Gorantla et al. & Chen et al.):

“Regular” chitosan is well suited for mechanically robust microneedles, while CMC stands out in hydrogel-based applications due to its high solubility and bioactive properties.

Therapy with a Future – Even Without Antibiotics

The microneedle patches rely on a dual action: they effectively eliminate bacteria without using classical antibiotics, while also modulating the skin’s immune response. This not only reduces infection risk but also improves scar formation and healing time.
The combination of nanotechnology, chitosan, and bioinspired microneedle design opens a completely new path in wound care - efficient, sustainable, and especially relevant in times of rising antibiotic resistance.

Conclusion
This development impressively demonstrates how modern materials science and natural substances like chitosan can together solve complex medical problems. The future of wound healing is minimally invasive, biologically intelligent - and potentially chitosan-based.

Sources
Hu et al. (2025): High-Entropy Nanozyme‑Driven ‘Chinese Acupuncture’ Hydrogel Microneedles for Combined Therapy of Infected Scalds
Jayakumar et al. (2011) – Biomaterials based on chitin and chitosan in wound dressing applications, Biotechnology Advances 29 
Mei-Chin Chen et al. (2012): Chitosan microneedle patches for sustained transdermal delivery of macromolecules, Biomacromolecules 2012
Srividya Gorantla et al. (2021): Chitosan-based microneedles as a potential platform for drug delivery through the skin: Trends and regulatory aspects, Int J Biol Macromol

First published on 10th of July 2025

Revised on 10th of July 2025