About us & WPs

At the Centre of Excellence (CoE) in Materials-driven Solutions for Combatting Antimicrobial Resistance (MADNESS), we develop innovative strategies to address one of the world’s most pressing health threats.

Antimicrobial resistance (AMR) refers to the ability of bacteria, viruses, fungi, and parasites to resist the effects of antimicrobial drugs that were previously effective in controlling their growth and spread. This phenomenon poses a serious threat to public health, as it makes it difficult or even impossible to treat infectious diseases leading to longer hospital stays, higher healthcare costs, and increased mortality rates. It has been suggested that by 2050 AMR could be responsible for up to 10 million deaths per year and a looming economic catastrophe. In 2019, the World Health Organization (WHO) listed AMR as one of the top 10 global health threats.

Within the CoE, we leverage our extensive experience and expertise in state-of-the-art materials, instruments, and methods to develop alternative pharmacological, non-pharmacological and combinatorial solutions for combatting AMR. Our research focuses on a range of promising materials-driven strategies, accelerated by the integration of artificial intelligence (AI) into our development processes. We also apply antimicrobial strategies in wound healing and tissue regeneration.

AMR is a result of the rapid evolution of microbes through mutations and DNA transfer, allowing them to counteract antibiotics and develop resistance mechanisms. Moreover, the situation worsens when individual microbes form biofilms, which is an often overlooked but serious hazard. Biofilms are colonies of microorganisms that adhere to surfaces, such as teeth, mucosa, or medical implants. Within biofilms, bacterial cells can display up to a 1,000-fold increase in antibiotic resistance, compared to individual bacteria, making it challenging to completely eradicate the infection.

As the efficacy of current antibiotics wanes, combined with insufficient efforts to develop new antibiotics, alternative approaches are urgently needed to efficiently treat infectious diseases and combat AMR. In the fight against AMR, it is also crucial to establish strategies to prevent biofilm formation and to address biofilm-induced infections.

Our work is structured into 6 work packages. In WP1 a–c, we develop advanced nanoparticles (NPs) to facilitate microbe/biofilm eradication. We build on our expertise on nanomaterial development stemming from synthetic and natural polymers as well as inorganic materials to derive research towards advanced functional biomaterial systems for efficiently eradicating microbes and suppressing the formation of biofilms. We apply NPs in the treatment of infected wounds (WP2) and tissue defects (WP3). The work is supported by the development work by AI-aided materials design (WP4) and advanced real-time and label-free surface analytical tools to get in-depth understanding of interactions between biomaterial systems and microbes through assessments on the bacterial uptake or membrane disruption (WP5), and by actions to promote clinical translation (WP6).

MADNESS work packages

WP 1a: Woody polyphenols as inherently antimicrobial NPs

Lead: Chunlin Xu and Xiaoju Wang

Natural polyphenols such as lignin and tannin can be derived from side-stream biomasses via modern biorefinery. Thanks to their inherent antimicrobial property, these natural polymers are attractive building blocks for creating antimicrobial nanomaterials.

Expected results: Correlation of polyphenol structure to antimicrobial efficacy of NPs will be established, and high-efficacy antimicrobial polyphenol NPs will be developed.

WP 1b: Sustainable and functional polymeric NPs as antimicrobial drug carriers

Lead: Kuldeep K. Bansal, Carl-Eric Wilen and Jessica Rosenholm

Using renewable jasmine lactone, we have recently created and patented a new polymeric material named poly(jasmine lactone) (PJL) via ÅAU. PJL provides a special means for the inclusion of functional groups of interest in its backbone, therefore permitting customized changes that can be used to fight AMR. Once functionalized, modified PJL can show antimicrobial activity on its own (cationic polymer) and could show synergistic effects by increasing the activity of encapsulated drugs that disrupt the microbial cell membrane, interfering with cellular processes, inhibiting enzyme activity, or generating oxidative stress inside the microorganisms. We aim to utilize these polymers to fabricate NPs/micelles loaded/conjugated with antimicrobial drugs that are already categorized as resistant to infections. We will also look at the possibilities of newly created synthetic mimics of antimicrobial peptides generated by UiT (Arctic University of Norway). Together with WP4 and WP5, we will assess the effectiveness of developed blank and drug-loaded NPs/micelles in overcoming AMR and eliminating biofilms in suitable models.

Expected results: Due to nanoscopic size range and cationic charge of PJL NPs/micelles, we expect enhanced cell membrane permeability, and consequent delivery of active agents with antimicrobial activity across biofilms. Issues associated with therapeutic agents such as toxicity, poor solubility and stability can be overcome by employing NP technologies.

WP 1c: Inorganic NPs as genetic construct carriers

Lead: Hongbo Zhang and Jessica Rosenholm

Porous inorganic nanoparticles, including metal-organic frameworks (MOFs) and mesoporous silica nanoparticles (MSNs), have many benefits that can be exploited in delivering fragile biomolecular drugs for treating AMR. Recently, it has been found that antimicrobial resistance genes (ARGs) are main determinants of AMR. Herein, we will utilize porous inorganic nanoparticles to deliver mRNA, CRISPR/Cas9, plasmids, and siRNA as novel strategies to tackle AMR by regulating the ARGs. 

Expected results: Utilizing these delivery platforms, we aim to conquer the current limitations of lipid NPs for the delivery of genetic constructs. We expect that these materials exhibit significantly improved stability during both storage (cold-chain) and application, as well as provide sustained intracellular release. By effectively delivering genetic constructs across biofilms in a targeted and controllable manner, AMR can be reversed.

Lead: Xiaoju Wang

Creating antimicrobial surfaces is an important engineering step to integrate antimicrobial polymers and nanomaterials into medical device designs for achieving therapeutic effects.

Expected results: We focus on increasing the antibiofilm activities of medical textiles with cationic antimicrobial polymers, whereby a bioelectronic device for combinational AMR therapy will be developed further.

Lead: Peter Uppstu

Large bone defects are often treated with tissue transplanted from the patient or a suitable donor. Because of the inherent drawbacks of bone transplants, such as donor site morbidity, risks of disease transmission, and lack of donor tissue, there is a need for synthetic three-dimensional templates that support tissue growth. Infected defects, that are very difficult to treat, require release of antimicrobial agents from the template for infection control.

Expected results: We aim to introduce a synthetic polymer-based bone regeneration template with controlled release of bioactive agents designed for bone tissue regeneration in large, even infected defects, which are notoriously difficult to treat.

Lead: Sébastien Lafond and Ivan Porres Paltor

Recently, AI and ML have gained significant traction in various stages of the drug and nanomedicines discovery process, including drug design and formulation, simulation, drug screening, and even clinical trial phases. ML techniques can facilitate the prediction of properties of drug formulations and aid in reducing the vast design space. This WP will focus on developing new AI-based simulation approaches to not only shorten the design life cycle, but also to provide detailed information on how to design optimal nanomaterials. 

Expected results: We expect to deliver an AI model which enables optimized design of NPs as effective antimicrobial agents.

Lead: Tapani Viitala

The mode of action of NPs in biofilms is still poorly understood, and studies on the interaction of NPs and biofilms are limited. Due to their intricate nature, it is difficult to study the kinetics of biofilm formation and growth, as well as to determine the structural properties of biofilms. In this WP, we develop and implement new analytical platforms based on multi-parametric surface plasmon resonance (MP-SPR) and impedance-based quartz crystal microbalance techniques (QCM-Z) for real-time label-free measurements of bacterial adhesion and biofilm growth kinetics and structure on surfaces, and the effect and interaction kinetics of new treatment modalities with biofilms.

Expected results: We expect to renew the analysis landscape for biofilms and collectively provide a better understanding on how biofilms grow, how to prevent biofilm growth, eradicate biofilms, and treat microbial infections by combining the additional information provided by the new analytical platforms with the information obtained by traditional assays.

Lead: Carl-Eric Wilén

We aim to advance our materials toward clinical applications through strategic collaborations with key partners in clinically relevant settings.