Research: Advancing the future of healthcare: a look at research collaborations between LKCMedicine and NTU College of Engineering

In 1898, Marie Curie and her husband, French physicist Pierre Curie, discovered two chemical elements: polonium and radium. Their discoveries led to them winning the Nobel prize - Marie's first of two - and creating a new field in science: radioactivity. With their research, Curie later invented mobile X-ray units during the first World War which saved many lives.

For centuries, research has played an important role in the knowledge and treatment in medicine. Today, technology advancements have changed the way healthcare professionals practise medicine and provide treatments to patients. We speak to scientists from LKCMedicine and NTU College of Engineering to find out how they are collaborating to advance healthcare research. 

NTU Institute for Health Technologies (HealthTech NTU)

HealthTech NTU aims to promote inter-disciplinary collaboration in translational biomedical research by facilitating functional integration between engineers, scientists, clinicians, and entrepreneurs, particularly across six engineering schools of NTU and LKCMedicine. Co-Executive Director LKCMedicine Associate Professor of Stem Cell Science and Regenerative Medicine Yen Choo shares more about the institute.

_{A/Prof Choo shares about what HealthTech NTU does}

Q: What are the objectives of HealthTech NTU?

A/Prof Choo: The objectives of HealthTech NTU are to develop and translate healthcare innovations arising from cutting edge interdisciplinary research.

Q: How will LKCMedicine work with other engineering schools to deliver impactful innovations that address healthcare challenges?
A/Prof Choo: HealthTech NTU will pull together teams of engineers, scientists and clinicians to address unmet medical needs. LKCMedicine and its clinical partners (such as the National Healthcare Group) contribute essential knowledge of disease biology, clinical practice, medicinal product regulation and health economics. HealthTech NTU will also work closely with NTUitive and LKCMedicine's Office of Innovation and Entrepreneurship to proactively translate research outcomes to industry.

Q: Why is it important for LKCMedicine to work with other engineering schools? 

A/Prof Choo: The next generation of biomedical innovations will undoubtably arise from a convergence of disciplines and approaches. In this context one of the big competitive advantages of LKCMedicine is to leverage the enormous strength of NTU throughout the engineering disciplines. The role of HealthTech NTU - and indeed the grand challenge in any technological university with a medical school - is to facilitate this cross-pollination, particularly between the engineers and clinicians.

Research project: Drug eluting dressings to promote diabetic wound healing

Lead Principal Investigator: LKCMedicine Professor David Becker

Co-Investigator: School of Chemical and Biomedical Engineering Associate Professor Chew Sing Yian

Collaborator/Research Associate: Leigh Edward Madden

PhD student: Chin Jiah Shin

Q: Do share with us what this research is about.

Prof Becker: We are trying to find ways to improve the wound healing process when it has gone wrong like in human chronic wounds.

A/Prof Chew: This research looks at deriving bio-mimicking scaffolds that are endowed with drugs (DFO and/or Connexin-43 antisense oligonucleotides) to enhance diabetic wound healing.

Q: What is your role in this research?

Prof Becker: I am the biologist PI and I have a lot of experience studying wound healing and translating lab findings into drugs and testing them in clinical trials.

Leigh: As part of this research, I am responsible for assessing the efficacy of the dermal substitute combined with a therapeutic compound in promoting wound healing in murine diabetic wound models. We want to evaluate the impact of the polymeric scaffolds, created by Chin Jiah Shin, with controlled drug release in these in vivo models.

Ms Chin: I mainly focus on the design and construction of a dermal substitute that aims to promote the healing of full thickness of chronic wounds. This research strives to establish a platform that can both serve as dermal substitute and a sustained drug delivery system. Using my biomedical engineering background, I can better understand the needs from both perspectives – biology and engineering.

Q: How will your expertise in tissue repair and regeneration be applied in this research? 

Prof Becker: I provide the team with guidance in the formulation of the experiments and how they should be analysed. They are skilled at what they do but occasionally I can help with the interpretation of some difficult to read histology and teach them what to look for themselves.

A/Prof Chew: My lab specialises in scaffold design and sustained non-viral drug/gene delivery for tissue regeneration applications. For this project, we are contributing in terms of the design, optimisation and fabrication of bioengineered scaffolds using techniques such as electrospinning. By using this approach, it allows us to obtain scaffolds with architectures that mimic the natural extracellular matrix in the body. Furthermore, we can control the process to include drugs/genes to provide localized and sustained delivery of these therapeutics. In doing so, drugs will remain at the site of injury for the desired treatment duration.

Q: How will drug eluting dressings help promote diabetic wound healing? 

Prof Becker: This is not just aimed at diabetic wounds, such as diabetic foot ulcers, but also venous leg ulcers and pressure ulcers. Many of these are just treated once a week and if a drug is applied it is likely to have been degraded within 24 hours. The scaffolds can provide a sustained release of drugs for over a week. It is hoped that this will prove to be more effective in the treatment of chronic wounds

Q: Why did LKCMedicine decide to collaborate with the College of Engineering for this research collaboration?  

Prof Becker: The engineers have great skills in generating scaffolds designed to deliver drugs and promote tissue repair. We have a lot of experience in the biology of wound healing with different preclinical and clinical models. Working together we can achieve far more than we could working alone.

A/Prof Chew: This is an interdisciplinary collaboration that combines biomedical engineering scaffold design and drug/gene delivery with skin biology. 

Q: What does the collaboration hope to achieve? 

Prof Becker: We hope to find a way to improve the healing of a perturbed wound using novel drugs and delivery methods. If this proves to be effective, we will file a technological disclosure to NTUitive to see if it is patentable. Should this be the case we will seek funding for second species studies using our porcine perturbed healing model.  

This can mimic many of the features of human chronic wounds unlike most available models where healing is just delayed by a couple of days at most.  If we can promote healing in this model it is more likely that our approach would work in human. If we generate positive results here, we would (like to) seek funding for GMP manufacture and testing to move into clinical trials.

Ms Chin: Ultimately, this research hopes to construct a dermal substitute that can both provide physical and biochemical cues (through the delivery of drugs) to encourage difficult-to-heal wounds such as chronic wounds.

Research collaboration: Targeting bacterial membrane biology with novel main chain cationic polymers
Lead Principal Investigator/Co-Investigator: LKCMedicine Assistant Professor Kevin Pethe and Professor Mary Chan

Q: Tell us what this research is about

A/Prof Pethe: The emergence and rapid spread of bacterial resistance to all classes of antibiotics coupled with the slowness of new antibacterial agent development has led to a global public health crisis. New agents, which attack still-vulnerable targets in bacterial biology and are less susceptible to resistance, are urgently needed. The bacterial membrane is the last frontier for antibacterial drug development that is thought to be less vulnerable to the emergence of resistance.

Q: What is your role in this research?

A/Prof Pethe: I provide expertise in microbiology and infectious diseases. It is important to note that we are also collaborating extensively with NCID/TTSH and Imperial College London.

Prof Chan: I am the lead principal investigator in this collaborative research programme. My group designs new antimicrobial polymers with more potent and broad-spectrum antimicrobial activities while inducing low drug resistance and low cytotoxicity.   

_{(From Left) LKCM Assoc Prof Kevin Pethe, SCBE Prof Mary Chan and PhD student Zhang Kaixi}

Q: Why is it important to target bacterial membrane biology with novel main chain cationic polymers?  
Prof Chan: While membrane-active antibacterial agents, principally cationic peptides/polymers, have been studied for decades, their mechanisms of action remain poorly understood and their typically high toxicity and low metabolic stability have hindered therapeutic use. Though the diversity of peptides and polymers is in principle vast, studies to date have tended to focus on hydrophobic and electrostatic interactions via cationic charges, which promote physical disruption/permeabilisation of anionic bacterial cytoplasmic membrane. However, bacterial surface membranes are vastly different from mammalian cell surface membranes and other unique surface membrane components and characteristics may be exploited as targets for novel antibacterial polymers. Better understanding of mechanisms of membrane biology perturbation and exploration of more diverse polymer structures may lead to the discovery of much needed new antimicrobial mechanisms that selectively attack bacterial membrane biology.

Q: What is the goal of the collaboration?

A/Prof Pethe: The overall goal is to develop cationic beta-peptides targeting bacterial membranes for a variety of hospital-acquired bacterial infection. We are targeting methicillin-resistant staphylococcus aureus (MRSA) and gram-negative superbugs of the ESKAPE family.