Institute of Bioengineering and Nanotechnology, Singapore
www.ibn.a-star.edu.sg

Researchers from the Institute of Bioengineering and Nanotechnology (IBN) in Singapore, in collaboration with IBM Research say that they have developed the firstever antimicrobial hydrogel that can break apart biofilms and destroy multidrug-resistant superbugs upon contact.

Fig. 1a and b - Shown on the left is a mature and healthy MRSA biofilm. After the hydrogel is applied, the biofilm is destroyed, as shown on the right. The small portion of cells that remain have an extremely disrupted membrane, preventing drug resistance.
Tests have demonstrated the effectiveness of this novel synthetic material in eliminating various bacteria that are the leading causes of microbial infections, and preventing them from developing antibiotic resistance. They say that this discovery may be used in wound healing, medical device and contact lens coating, skin infection treatment, and dental fillings.

Dr. Yi-Yan Yang, Group Leader at IBN said: “The mutations of bacteria and fungi, and misuse of antibiotics have complicated the treatment of microbial infections in recent years. Our lab is focused on developing effective antimicrobial therapy using inexpensive, biodegradable, and biocompatible polymer material. With this new advance, we are able to target the most common and challenging bacterial and fungal diseases, and adapt our polymers for a broad range of applications to combat microbial infections.”

More than 80% of all human microbial infections are related to biofilms, which can colonize on almost any tissue or surface, and contribute significantly to hospital-acquired infections. In Singapore, antimicrobial drug resistance is a major healthcare problem because of the extensive use of antibiotics and medical equipment, such as intravascular catheters and orthopedic implants in patients.

A report in the Journal of Hospital Infection in 2011 shows that patients in Singapore with microbial infections were 10.2 times more likely to die during their hospitalization, had 4.6 times longer hospitalization, and incurred 4 times higher hospitalization cost compared to patients with no infections.

IBN’s Nanomedicine group has conducted research on polymer and peptide nanoparticles as antimicrobial agents since 2007 under Yang’s guidance. Her lab has published 15 papers and filed 10 patents on their antimicrobial technologies.

IBN Executive Director Professor Jackie Y. Ying explained: “As a multidisciplinary research institute, IBN believes that effective solutions for complex healthcare problems can only emerge when different fields of expertise come together. Our longstanding partnership with IBM reflects the collaborative creativity across multiple platforms that we aim to foster with leading institutions and organizations. By combining IBN’s biomaterials expertise and IBM’s experience in polymer chemistry, we were able to pioneer the development of a new nanomaterial that can improve medical treatment and help to save lives.”

How the Gel Works

The hydrogel targets the bacteria and fungi behind seven of the most common hospital-acquired infections, such as MRSA (methicillin-resistant Staphylococcus aureus), VRE (vancomycinresistant enterococcus), multidrug-resistant Acinetobacter baumannii,and Klebsiella pneumoniae, E. coli, Candida albicans, and Cryptococcus neoformans fungi. (See Figures 1a and b)

With more than 90% water content, the hydrogel is comprised of a novel polymer material jointly developed by IBN and IBM Research in 2010. When mixed with water and heated to body temperature, the polymers spontaneously form into a moldable gel, which allows the gel to target multidrug-resistant biofilms at various parts of the body and surfaces without being flushed away. Once the antimicrobial function is activated and performed, the biodegradable gel can be naturally eliminated by the body.

The researchers say that when it’s applied to contaminated surfaces, the hydrogel tears apart the membranes of the microbes in the biofilms and kills harmful cells. This is made possible by an electrostatic interaction between the positively charged gel and the negatively charged bacterial or fungal cells. Unlike current antibiotics, which only target the internal machinery of the microorganisms, this new mode of action eliminates the superbugs completely and prevents any recurring infections. The antimicrobial gel can also be applied to surfaces to prevent antibiotic-resistant microbes from forming on wounds, medical devices, and implants.

“Bacterial biofilms are a serious health threat and the ability to disperse such films is critical. The soft consistency of our non-toxic materials makes them ideal for injectable and topical applications as well as coatings and lubricants for medical devices such as catheters,” said Dr. James Hedrick, Advanced Organic Materials Scientist, IBM Research.

“Whether it’s designing degradable materials to eliminate polymers occupying landfills or new antimicrobial hydrogels that don’t have drug resistance, our partnership with IBN has allowed us to take what the industry has deemed really important and create solutions that are applicable to many technologies in medicine,” he said.