The Italian Ministry of University and Research has defined the recipients for the new funding cycle of FIS 2 – the Italian Science Fund, designed to support frontier research projects with high scientific and clinical impact.

Among the selected projects is the one coordinated by Mattia Loppini, orthopedic surgeon at the Hip Orthopedic and Prosthetic Surgery Unit at the Humanitas Research Hospital and Associate Professor of Diseases of the Musculoskeletal System at Humanitas University, in collaboration with Roberto Rusconi, Associate Professor at Humanitas University and head of the Applied Physics, Biophysics and Microfluidics Laboratory.
The project focuses on one of the most critical complications in orthopedic surgery: periprosthetic joint infections (PJI).

What are periprosthetic infections?

Periprosthetic infections develop around a joint prosthesis, such as those of the hip or knee. They can occur immediately after surgery or months or even years later, when bacteria from other parts of the body reach the implant through the bloodstream.
The implant surface can provide microorganisms with an environment suitable for adhesion and nesting within microscopic irregularities of the material, making these infections very difficult to treat.
For this reason, PJIs require specific diagnostic and therapeutic pathways.

A growing clinical challenge

“Every year in Italy,” explains Loppini, “about 200,000 prosthetic implants are performed. Even if only 2% develop an infection, the high overall volume means that PJIs represent the leading cause of prosthetic revision within the first year after surgery and one of the main reasons for reintervention in the long term.”

The consequences for patients can be significant: persistent pain, functional limitations, and the need for additional surgical procedures. It is also a major issue for the healthcare system, which must deal with repeated hospitalizations, prolonged antibiotic therapies, and complex interventions.

Why are they so difficult to treat?

The difficulty in treatment stems from the ability of bacteria to adapt to the implant environment.
“When microorganisms colonize the surface of an implant,” explains Rusconi, “they can form biofilms, protective structures that make them less sensitive to antibiotics and harder for the immune system to eliminate.”

Within biofilms, bacteria modulate their metabolism and grow more slowly, making them harder to isolate using traditional cultures.
“Furthermore,” Rusconi continues, “the same microorganism can modify its behavior depending on the prosthesis material or the local immune response, activating genes that affect its virulence and resistance.”

To study these mechanisms, the project will analyze 120 clinical samples (60 infected and 60 non-infected) collected at the Humanitas Research Hospital, using genomic sequencing and in vitro reconstruction of the prosthetic environment, to investigate biofilm formation and the interaction between bacteria and the immune system.
This will also allow the evaluation of potential therapeutic strategies under controlled yet realistic conditions.

Towards more accurate diagnoses and new therapies

Starting in February 2026 and continuing for three years, the project aims to identify new diagnostic markers and therapeutic targets through the integration of clinical data, genomic analyses, and advanced experimental models.

“Our goal,” states Loppini, “is to recognise the different forms of infection early on, so as to guide more effective therapeutic decisions.”
Rusconi adds: “Studying biomaterials, microbes, and the immune response together is essential to understand the mechanisms underlying these infections and identify new treatment opportunities.”

In a field where surgery, microbiology, and biophysics are increasingly intertwined, the project represents a decisive step toward more precise diagnoses, more targeted therapies, and better outcomes for patients, while also helping reduce the impact of periprosthetic infections on the healthcare system.