Maribor researchers develop bioactive coatings for implants

The coatings can contain analgesic, antimicrobial and anti-inflammatory active substances that are released in the immediate surroundings of the implant in controlled concentrations.

This reduces the side effects that may otherwise be present with systemic treatment. Due to their properties and the controlled release of the active substances the coatings improve the effectiveness of the implant's integration into the human bone.

"We are developing solutions that will significantly improve orthopaedic surgeries and prevent or at least minimise post-operative problems," says Matjaž Finšgar, head of the Laboratory for Analytical Chemistry and Industrial Analysis at the Faculty of Chemistry and Chemical Engineering (FKKT).

Finšgar was one of the winners of the 2023 Zois Prizes, the national science awards, for significant achievements in the development of unconventional tools in analytical chemistry.

Key solutions for ageing society

He says such solutions are especially important in light of an ageing population, chronic obesity, orthopaedic injuries and osteoarthritis as some of the main reasons for the increasing number of orthopaedic surgeries.

These factors contribute to the staggering costs of healthcare in Slovenia and worldwide. Orthopaedic surgeries are complex. They cause tissue damage and pose high risks, and in extreme cases can even result in death.

Therefore, the main goal of the development of modern implants is to ensure long implant survival with good functionality, Finšgar explains.

Currently, orthopaedic implants are mostly made of various metals such as stainless steel and titanium alloys. The body may recognise them as foreign bodies and start rejecting them, which can lead to complications or the need for follow-up surgery.

This makes the development of advanced biomaterials for orthopaedic implants that allow better integration of the artificial implant into the living bone and prevent potential post-operative complications very topical.

Better performance of 3D printed implants

The Maribor researchers are currently working on the development of metal implants using 3D printing, which is being carried out in collaboration with the Laboratory for Additive Manufacturing at the Maribor Faculty of Mechanical Engineering under the leadership of Igor Drstvenšek.

3D makes it possible to produce tailor-made implants. This means that the shape of the implant can be adapted to the needs of patients and surgeons using diagnostic images and computer modelling. The 3D printing laboratory also 3D prints implants from TiAlV, a titanium alloy known for its good durability and biocompatibility.

"The aim of this development is to make an implant that performs better than conventional implants currently available - that is, to fill a defect and preserve the biomechanical balance, and to give the patient a long-term solution with as few complications as possible," Drstvenšek says.

One of the key advantages of 3D technology compared to traditional procedures such as turning and milling is that it can also print a special pore structure on the implant surface, the size and depth of which is adjusted to the expected stress in the body.

The pores give the implants porosity, which can improve bone growth and adhesion, increase friction in the body, while the pores also serve as a site for various forms of delivery systems for active substances, such as polymer coatings and hydrogels, Drstvenšek explains.

Advanced methods to develop different bioactive coatings

The interdisciplinary collaboration of Maribor researchers has produced the design of several different bioactive coatings. Among others, they have developed layered coatings with alternating layers of biodegradable polymers and active substances, where the number of layers can easily control the release of active substances into the implant surroundings.

In collaboration with the Laboratory for Separation Processes and Product Engineering of the Maribor Faculty of Chemistry and Chemical Engineering, headed by Željko Knez, they have developed bioactive coatings applying advanced methods involving the use of supercritical carbon dioxide.

This means carbon dioxide is held in a state above the critical point where substances are physically located between gases and liquids. Researchers are exploiting such methods to create porous polymer coatings as carriers for active pharmaceutical ingredients.

Advanced techniques to test efficiency of coatings

To make bioactive coatings truly safe and effective, researchers test their properties using interdisciplinary experimental approaches and analytical techniques.

The Laboratory for Analytical Chemistry and Industrial Analysis determines whether the integration of active substances into bioactive coatings has been successful, whether their distribution is homogeneous, and their release pathway. The active substances have to be released in specific concentrations and at specific times to achieve the desired effect, the laboratory's head Finšgar explains.

To analyse the chemical structure of the prepared coatings, his laboratory uses advanced surface-sensitive analytical methods such as tandem mass spectrometry of secondary ions with time-of-flight analysers (MS/MS ToF-SIMS) and X-ray photoelectron spectroscopy (XPS).

ToF-SIMS and XPS, in combination with the ion source of argon gas clusters, are completely new thing in Slovenia and a rarity elsewhere, says Finšgar. The two devices, worth around EUR 2 million, were acquired as part of a project co-funded by the Ministry of Higher Education, Science and Innovation and the EU.

Preclinical studies test human cell response

Preclinical studies conducted on the coatings at the Institute of Biomedical Sciences at the Maribor Faculty of Medicine assess the safety of the coatings for use, while also evaluating their effectiveness for bone ingrowth under laboratory conditions.

They use a wide range of tests to verify the response of human bone (and other, e.g. mesenchymal stem) cells to metal implants with bioactive coatings.

"We are interested in how well the cells respond to the material and how this might contribute to better fitting or better acceptance of the implants by the body," the head of the institute Uroš Maver says.

"We are interested not only in the growth of the cells and the maintenance of their properties when exposed, but also in their formation of important 'non-living' bone components (what we call the mineral part of the bone). Using cell-based assays, we can compare materials in the laboratory and select the best ones for use in the implants and, of course, discard the unsuitable ones," he explains.

Their innovative implants with bioactive coatings are suitable for human application. However, clinical studies are a key step they need to take before they can actually be brought to market. These are a major financial and logistical challenge and they hope for major European projects and potential investors.

"Our long-term vision is to design personalised biomedical devices tailored to the patient's anatomy and pharmacotherapy," Maribor researchers say, adding that even the smallest contribution to the science in this field can greatly improve the success rate of orthopaedic procedures.