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Bacteria Biofilm as bio-factory for tissue regeneration

Periodic Reporting for period 2 - BIOACTION (Bacteria Biofilm as bio-factory for tissue regeneration)

Reporting period: 2024-04-01 to 2025-09-30

Fighting infections and microbial resistance presents an ever-pressing challenge in the field of healthcare. Implant-associated infections, for example, increase the risk of device rejection, compromising patient health and contributing to the growing problem of antimicrobial resistance. Standard treatments, including prolonged antibiotic regimens, often prove futile against these resilient bacterial communities, exacerbating the issue.

In this scenario, Bioaction takes a bold and innovative stance, departing from traditional approaches: rather than combating pathogenic bacteria head-on, Bioaction leverages them as valuable allies in promoting tissue regeneration for better implant integration. This novel perspective offers a paradigm shift in addressing infections. The project is developing functional bio-hydrogels capable of triggering local remodelling of physiological processes to accelerate healing and stimulate bone growth and designed as injectable materials or implant coatings for minimally invasive delivery.
Significant progress has been achieved in the first year of the BIOACTION project. This includes the selection of polymers or peptides for the development of bio-hydrogels based on their mechanical properties, bioactivity, biocompatibility and stability. Formulations for injectable hydrogels and for implant coatings were selcted. Additionally, work started on preparing lipid-based liposomes with a two-faced outer shell containing lipoplexes for engineering bacteria. Furthermore, we started the genetic engineering of biological carriers (Bacteriophages- BPs) to transform biofilm-associated bacteria for specific protein production. We have collected BPs targeting specific bacteria in the biofilm and assess protocols for optimal growth and infection. The safety of both neat and composite injectable hydrogels was evaluated in terms of cell viability and proliferation which leads the pathway for future assessment of the in vitro and in vivo efficacy BIOACTION hydrogels.

During RP2, BIOACTION advanced the development of next-generation biomaterials by creating injectable bio-hydrogels, enriched with osteoinductive signals to support bone regeneration. In parallel, synthetic peptide hydrogels—with and without added osteogenic components—were produced and fully characterized, demonstrating their ability to promote cell proliferation, osteogenic differentiation, and angiogenesis. BIOACTION also achieved the successful loading of these hydrogels with its biological carriers. Hydrogels containing multicompartment Janus liposomes (MJL) showed no cytotoxic effects, while bacteriophage-loaded hydrogels efficiently released infective phages capable of targeting bacteria. Ongoing studies are now investigating the in vitro transfection efficiency of these innovative delivery systems, while in vivo models for dental and orthopedic applications were established and will soon start.
Within the project, researchers will actively validate the technology using clinically relevant models for dental implants and permanent transcutaneous prostheses. However, the transformative impact of Bioaction extends far beyond these specific cases. By reducing reliance on extended antibiotic therapies and mitigating failure rates, this pioneering project holds the power to revolutionise infection treatment methods. In the long run, Bioaction strives to enhance patients’ quality of life while making significant contributions to the worldwide battle against antimicrobial resistance.
Overview of the components of BIOACTION’s bio hydrogel.
Bio hydrogel application, reprogramming of biofilm, and production of regenerative proteins.
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