In-Situ Fabricated Living Nanofiber Scaffolds with Stem Cell-Chlorella pyrenoidosa for Synergy Enhance Diabetic Wound Healing

Abstract

Stem cell therapy has emerged as a promising strategy for managing chronic wounds. However, its effectiveness in diabetic wound healing remains limited due to sustained hypoxia, excessive reactive oxygen species (ROS), and a persistent inflammatory microenvironment. Developing harmful-microenvironment-adapted reparative materials could enhance stem cell survival and function, thereby improving therapeutic outcomes. This study developed a stem-cell-supported multifunctional bio-scaffold, composed of polyethylene oxide/polyvinyl butyral (PEO/PVB) nanofiber scaffolds and umbilical cord mesenchymal stem cells (UC-MSCs), named living nanofiber scaffolds (LNFS). A three-dimensional (3D) PEO/PVB nanofiber scaffold with a controlled gradient structure was first fabricated using in-situ dual-component alternating electrospinning. By integrating in-situ cell electrospinning with this technique, UC-MSCs were evenly embedded within the scaffold, achieving high cell density and viability. Furthermore, Chlorella pyrenoidosa (CP) was incorporated into the LNFS to supply oxygen, scavenge ROS, and reduce glucose levels, thereby enhancing the synergistic effect of CP and UC-MSCs. In vivo experiments demonstrated that LNFS@CP effectively absorbed wound exudate, suppressed inflammation, promoted collagen deposition and angiogenesis, and ultimately accelerated diabetic wound healing. This study presents a non-contact 3D stem cell delivery system and a multifunctional bio-scaffold that synergistically enhances the effects of CP and UC-MSCs, providing a novel strategy for wound treatment.

Keywords

In-situ cell electrospinning / Stem cell delivery / Chlorella pyrenoidosa / Living nanofiber scaffolds / Diabetic wound healing

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Funding

Grants from the National Key R&D Program of China(2023YFC2411303)

Shanghai Oriental Talent Program

National Natural Science Foundation of China(82372513)

RIGHTS & PERMISSIONS

Donghua University, Shanghai, China