MSC-Integrated CuPB-BTB Coaxial Nanofibrous Scaffold for pH-Responsive Infection Monitoring and Antibacterial-Regenerative Wound Therapy

The healing process of chronic wounds is often hindered by recurring bacterial infections, inflammation, and inadequate tissue regeneration, which necessitates the development of innovative dressing materials capable of both infection detection and treatment. Herein, we report the development of a coaxial nanofiber scaffold made up of PCL-gelatin integrated with copper-doped prussian blue nanoparticles (CuPB), bromothymol blue (BTB), and mesenchymal stem cells (MSCs) for concurrent pH-sensitive detection of infection, drug delivery, and tissue regeneration. The coaxial architecture allowed compartmentalized integration of functional elements within the scaffold while preserving its biomimetic fibrous structure for wound dressing application. The release of CuPB nanoparticles, which serve as the source of the antibacterial copper component, imparted antibacterial properties, while BTB facilitated visual colorimetric detection of infection-associated pH changes, allowing real-time monitoring of wound status. The addition of the MSCs further augmented the regenerative potential of the scaffold through the paracrine mediated modulation of inflammation, angiogenesis, and extracellular matrix remodeling. In vitro assessment indicated the cytocompatibility, MSC compatibility, and hemocompatibility of the scaffold, with hemolysis less than 2%. In vivo assessment revealed that MSC-loaded CuPB-BTB coaxial nanofibers promoted wound healing more efficiently than the control group. Histological and immunohistochemical analyses further revealed improved tissue organization, enhanced angiogenesis as evidenced by VEGF expression, and increased α-SMA associated tissue remodeling. Hence, this multifunctional scaffold represents a promising theranostic wound dressing capable of integrating infection monitoring, antibacterial action, and MSC-mediated tissue regeneration for chronic wound management.