Layer-by-Layer Bioprinted Constructs Embedding Antimicrobial Agents with Regenerative Factors for Chronic Tissue Repair

Background

Chronic wounds, including diabetic ulcers, pressure ulcers, and burn injuries, are characterized by persistent infection, prolonged inflammation, and impaired tissue regeneration, making them difficult to treat using conventional wound dressings and antimicrobial therapies. Advanced biomaterial-based strategies are needed to simultaneously control infection and promote tissue repair.

Objectives

This study proposes an advanced layer-by-layer 3D bioprinted construct integrating antimicrobial agents, regenerative biomolecules, embedded nanosensors, and an Artificial Intelligence (AI)-based feedback system to enhance chronic tissue repair through controlled drug delivery and real-time wound monitoring.

Materials and Methods

A multi-material bioink composed of sodium alginate and Gelatin Methacrylate (GelMA), crosslinked with calcium chloride, was developed for extrusion-based 3D bioprinting. Silver nanoparticles and gentamicin-loaded Poly (Lactic-co-Glycolic Acid) (PLGA) microspheres were incorporated to provide sustained antimicrobial activity, while Mesenchymal Stem Cells (MSCs) and Vascular Endothelial Growth Factor (VEGF) were embedded to stimulate angiogenesis and tissue regeneration. Flexible nanosensors were integrated within the construct to continuously monitor wound pH and oxygen levels, and an AI-assisted control system dynamically regulated drug release in response to changes in the wound microenvironment.

Results

The proposed multifunctional construct demonstrated sustained antimicrobial activity with greater than 90% pathogen reduction, controlled drug release reaching approximately 95% cumulative release over 14 days, and enhanced regenerative performance with cell viability exceeding 90%, improved angiogenesis, and accelerated tissue coverage. The embedded sensing platform enabled continuous monitoring of physiological parameters, while the AI-based feedback mechanism facilitated adaptive and targeted therapeutic intervention.

Conclusion

The developed smart bioprinted construct integrates antimicrobial therapy, regenerative medicine, biosensing, and artificial intelligence into a single multifunctional platform for chronic wound management. This closed-loop therapeutic strategy has the potential to improve infection control, accelerate tissue regeneration, and enable personalized wound care, providing a promising foundation for future translational and clinical applications.