“Through natural selection, biological materials have evolved with remarkable shapes and extraordinary properties. What insights can we gain from their formation processes and functional mechanisms? Is it possible to replicate these precise biological formations synthetically in our laboratories, and if so, what potential benefits could this approach offer?”
Martin Andersson and his research group at the Department of Chemistry and Chemical Engineering at Chalmers University of Technology, Sweden, is interested in looking at how design principles found in nature can inspire the creation of materials and the development of medical devices aimed at addressing some of our most pressing health challenges. The group utilises nanochemistry to design bionanomaterials for applications in biomimicry, regenerative medicine, nanotoxicology and drug delivery.
“Nanochemistry originates from chemistry,” he said, “but it’s highly multidisciplinary. We aim to come up with new strategies for nanomaterials, develop new kinds of structures and work towards their application in helping patients.”
He pointed out that medical devices include implants, drug delivery, synthetic cells and sensing devices. Even a simple thing like a cane to assist walking is a medical device.
“They are also not new,” he continued. “We have been developing them for centuries. Examples include the Cairo Toe – a 3000-year-old wooden toe found in a burial chamber in Luxor, Egypt; examples of Trepanised Inca Skulls that date back 1600 years; and, iron dental implants dating from 300 BC found in Celtic gravesites.”
He also pointed out that many of the materials used routinely today were discovered by serendipity. For example, Spitfire crashes during World War II led to the finding that plexiglass was less damaging to eyes than ordinary glass and more easily accepted by eye tissue, eventually leading to the development of intraocular lenses.
From these early innovations many different types of devices are used in all types of surgery today. There has been a huge increase in hip and knee replacements with surgeons being able to treat patients earlier and devices lasting longer.
However, whenever you introduce a foreign material to the body there is a risk of infection and Andersson described this as the number one problem with the number of infections increasing. “Bacteria in biofilms can also survive exposure to antibiotics so reducing this bacterial adhesion is very important.”
And existing treatments will not necessarily help. Andersson focused in on the huge problem of antimicrobial resistance. “Nearly 1.3 million deaths were directly related to bacterial antimicrobial resistance in 2019 but nearly 5 million were associated. It’s estimated that by 2050 AMR will cause 10 million deaths annually. It’s a global crisis.”
And one we have known about for a long time. Alexander Fleming warned of the dangers of resistance when he won the Nobel Prize in Physiology or Medicine in 1945 for the discovery of penicillin. Resistance is mainly caused by the overuse and misuse of antibiotics, with the timespan for resistance formation shortening, and few new antibiotics being developed because there is no incentive for Big Pharma.
“We need better use of existing antimicrobials, education and awareness,” said Andersson. “Most people are simply not aware of the problem.”
“In the meantime, we need to develop more materials that prevent or hinder infection,” he added.
Borrowing from nature
He and his colleagues have therefore focused on biomimetic methods for creating medical implants, and on developing peptide-based alternatives to antibiotics, mimicking those in our immune system, to combat resistance.
Biomimetics or biomimicry is the emulation of the models, systems and elements of nature for the purpose of solving complex human problems. “It’s about mimicking biology in various ways. Looking at how nature solves problems and borrowing from nature to get inspiration,” he said.
Andersson highlighted two examples of his group’s work using this approach to create bioactive surface synthetic bone and contact killing surfaces using antimicrobial peptides.
“Bone is a fantastically complex material,” he said. “There is hierarchy and order, soft and hard parts. It’s very strong, but lightweight, flexible and regenerative. It’s difficult to copy in the laboratory.”
When an implant is introduced one of the challenges is to facilitate good osseointegration which is the connection between living bone and the surface of an implant (such as dental implants, joint replacements, and even prosthetic limbs). Good integration improves the stability, strength, function and longevity of the implant but poor integration means that the real bone may push out the implant leaving a gap which bacteria can colonise.
The aim is therefore to find new ways to prevent and treat implant-associated infections.
Andersson’s group have succeeded in creating a scaffold for producing bone-like calcium phosphates. These can be used as coatings on implants and to form bone-like nanocomposites which are compatible with the existing bone and strengthen integration. “We hope to win the race for the surface by facilitating reduced healing time and infection avoidance. The tiny particles can’t be seen with the naked eye, but they also have good wetting capacity which means they can increase blood flow and speed up healing.”
‘It took 13 years from the idea to market and was first used in a dental implant,” he explained. “It’s now used for implants throughout the body with reduced healing time and a high success rate – even in diabetic and sarcoma patients where it helps to prevent amputation.
“We hope to have more such products on the market soon.”
Natural born killers
The other project involves the introduction of antimicrobial peptides into hydrogel wound dressings to enable contact killing of bacteria. Antimicrobial peptides (or AMPs) are released from neutrophils and are part of the innate immune system with a wide range of neutralising effects against bacteria, fungi, parasites and viruses. They have historically been difficult to use clinically because they are sensitive, have low stability and require high doses. Andersson ‘s group has found a method to introduce them into wound dressings that allows them to maintain their activities and stability so that they can rapidly bind to and kill both gram-positive and negative bacteria. They can be used to prevent and treat infection.
“Our first clinical study involving 40 volunteers showed that they killed 99.9% of bacteria and removed endotoxins. They have since been introduced into animal medicine and we are currently going through the FDA regulatory processes for use in humans which we hope will be approved by next year.”
“Eventually it will be possible to use them for wound care, antimicrobial sprays, antibacterial coatings and in pre-surgical settings,” he added. The techniques would also have potential uses in treating burn wounds and in the beauty industry from which they have already had an approach.
He pointed out also that AMPs have multiple modes of activities – not just one target – and that bacteria would have to change their outer membrane to become resistant to AMPs.
Andersson also spoke of the challenges of getting such products to the market from the initial idea, through conceptual studies, to the practical application of these new technologies — transitioning from university labs to clinical and market settings. “Each journey is unique, but you need acceptance. It’s often easy to persuade scientists but the regulatory process and then the market is tricky. It takes substantial time to get market acceptance of new medical devices.”
Michelle Galloway: Part-time media officer at STIAS
Photograph: Noloyiso Mtembu