AniView Supports Biomaterial-Based Wound Repair Research: Fibrous scaffolds loaded with BMSC-derived apoptotic vesicles promote wound healing by inducing macrophage polarization

New progress has been made in biomaterial-based wound healing therapy through macrophage polarization regulation.

Researchers Ning Hu and Leilei Qin from the First Affiliated Hospital of Chongqing Medical University, together with Yonghua Yuan from Chongqing Medical University, have made new advances in the field of skin wound repair and regenerative medicine. Their findings have been published in “Genes & Diseases” (IF = 9.4, Q1 journal).

This study provides new insights into the development of BMSC-derived apoptotic body-loaded fibrous scaffolds for promoting wound healing through macrophage polarization regulation, offering a promising strategy for chronic wound treatment and immune imbalance-related diseases.

The skin is the largest organ in the human body and serves as the first line of defense against external damage. Following skin injury, the body initiates a series of precisely regulated repair processes, in which macrophages play a critical role. These immune cells exhibit remarkable plasticity and can differentiate into pro-inflammatory M1 macrophages or anti-inflammatory M2 macrophages depending on environmental signals. During normal wound healing, macrophages gradually transition from an inflammatory state in the early stage to a reparative state in the later stage, coordinating inflammation resolution, angiogenesis, and tissue remodeling. However, impaired macrophage polarization can lead to persistent inflammation, delayed healing, or chronic wound formation. Therefore, effectively promoting macrophage polarization toward the reparative M2 phenotype has become a key strategy for enhancing wound repair.

In recent years, mesenchymal stem cells (MSCs) have attracted significant attention in tissue regeneration due to their strong paracrine and immunomodulatory capabilities. Extracellular vesicles released by MSCs, particularly apoptotic bodies generated during apoptosis, have been shown to efficiently deliver bioactive molecules and regulate recipient cell functions. Previous studies have demonstrated that apoptotic bodies can be recognized and internalized by macrophages, promoting their transformation toward the M2 phenotype. However, the underlying mechanisms remain unclear. In addition, achieving sustained release and targeted delivery of apoptotic bodies at wound sites remains a major challenge for clinical translation.

In this study, the researchers successfully developed a polycaprolactone (PCL) fibrous scaffold loaded with bone marrow mesenchymal stem cell-derived apoptotic bodies (BMSC-ABs) and systematically elucidated its mechanism in promoting wound healing through macrophage polarization regulation. The scaffold enabled localized and sustained release of apoptotic bodies through electrospinning technology. Rich in microRNA miR-21a-5p, the released BMSC-ABs targeted and suppressed CCL-1 expression in macrophages, thereby driving the transition of M0 macrophages toward the reparative M2 phenotype.

The polarized M2 macrophages secreted anti-inflammatory factors, including IL-10 and TGF-β, effectively alleviating local inflammatory responses. Meanwhile, they enhanced the expression of angiogenic factors such as vascular endothelial growth factor (VEGF), synergistically promoting collagen deposition and new blood vessel formation. In animal models, the BMSC-AB-loaded scaffold significantly accelerated the healing process of full-thickness skin defects, demonstrating excellent biocompatibility and therapeutic safety.

This study is the first to reveal the molecular pathway by which apoptotic bodies regulate macrophage polarization through the miR-21a-5p/CCL-1 axis. Furthermore, it introduces a novel multifunctional composite material with sustained-release and synergistic therapeutic properties, providing important experimental evidence and strategic guidance for the treatment of chronic wounds and immune dysregulation-related diseases.

Experiments using AniView

In this study, the research team utilized AniView multimodal in vivo imaging system from Guangzhou Biolight Biotechnology to monitor the dynamic distribution and retention of BMSC-ABs at wound sites and surrounding tissues in mice. Experimental results showed that Cy7-NHS-labeled BMSC-ABs generated detectable fluorescence signals at the wound site for up to 2 days after administration. The signal intensity gradually decreased over time and dropped to less than 10% of the initial value at 2 days post-injection, indicating that locally injected BMSC-ABs could effectively remain at the wound area for a sufficient period to support therapeutic effects.

DOI: org/10.1016/j.gendis.2024.101388