Electrospinning Machine | In‑Situ Fabricated Living Nanofiber Scaffolds with Stem Cell‑Chlorella pyrenoidosa for Synergy Enhance Diabetic Wound Healing

Stem cell therapy has become a promising strategy for chronic wound management. However, its efficacy in diabetic wound healing is limited due to adverse effects from factors such as persistent hypoxia, excessive reactive oxygen species (ROS), and a prolonged inflammatory microenvironment. Developing repair materials that can adapt to these adverse microenvironments is expected to enhance stem cell survival and function, thereby improving therapeutic outcomes.

On September 10, 2025, Yuanyuan Liu from Shanghai University, Jiacan Su and Yuhai Ma from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and Shichu Xiao from the First Affiliated Hospital of Naval Medical University published a research paper titled "In-Situ Fabricated Living Nanofiber Scaffolds with Stem Cell-Chlorella pyrenoidosa for Synergy Enhance Diabetic Wound Healing" in the journal Advanced Fiber Materials. This study addresses the bottleneck of limited stem cell survival and function in diabetic wounds by innovatively proposing a synergistic therapy system combining stem cells and functionalized nanofiber scaffolds.

First, a three-dimensional gradient structured nanofiber scaffold of polyethylene oxide/polyvinyl butyral (PEO/PVB) was constructed via in-situ two-component alternating electrospinning technology. Combined with in-situ cell electrospinning, high-density, high-activity uniform loading of umbilical cord mesenchymal stem cells (UC-MSCs) was achieved, forming a "living nanofiber scaffold (LNFS)." Further integration of Chlorella pyrenoidosa (CP) endowed the scaffold with continuous oxygen supply and reactive oxygen species (ROS) scavenging functions, synergistically optimizing the wound microenvironment. In vivo experiments demonstrated that LNFS@CP significantly accelerated diabetic wound healing by improving exudate absorption, inflammation inhibition, collagen deposition, and angiogenesis.

Figure 1: Preparation of LNFS@CP using in-situ two-component alternating electrospinning technology.

As shown in Figure 1a, a portable electrospinning apparatus was used to achieve in-situ construction of LNFS@CP through alternating electrospinning technology, accelerating diabetic wound healing. Utilizing two-component alternating electrospinning technology, a composite multi-component gradient scaffold - LNFS@CP - was successfully prepared. This scaffold consists of nanofibers containing mussel adhesive protein (MP), PEO nanofibers loaded with UC-MSCs, and PEO nanofibers loaded with CP (Figure 1b). In vivo experiments demonstrated that the in-situ prepared LNFS@CP exhibited enhanced synergistic therapeutic effects, including oxygen production, ROS scavenging, inflammation inhibition, and promotion of angiogenesis, thereby improving the microenvironment and accelerating diabetic wound healing (Figure 1c).

Figure 2: In-situ alternating electrospinning technology constructs a two-component three-dimensional gradient structure scaffold, overcoming the mechanical and biological limitations of traditional single-component nanofiber scaffolds.

Figure 3: Combining in-situ cell electrospinning and alternating electrospinning technology achieves high-density, high-activity uniform distribution of UC-MSCs in three-dimensional scaffolds, overcoming the uneven cell distribution and inefficiency of traditional seeding methods.

Figure 4: CP proposes a "non-contact three-dimensional stem cell delivery" strategy, establishing a two-way synergistic therapy model of "microenvironment remodeling-stem cell function enhancement," providing a safe and novel engineered delivery platform for stem cell therapy.

Conclusion: This study proposes a "non-contact three-dimensional stem cell delivery" strategy, using a portable electrospinning device to construct in situ a multifunctional biological scaffold LNFS@CP that combines microenvironment regulation and stem cell function enhancement, providing an innovative solution for diabetic wound treatment. Furthermore, this work offers new insights into multi-dimensional synergistic interventions for tissue regeneration in complex pathological microenvironments, with significant clinical translation potential.

Paper link: https://link.springer.com/article/10.1007/s42765-025-00604-y