Munthar Kadhim Abosaoda

Non-healing wounds, such as diabetic foot ulcers, burns, and pressure injuries, represent a persistent clinical challenge, affecting an estimated 2–5% of the global population and accounting for annual healthcare costs exceeding USD 25 billion. Their failure to heal is driven by unresolved inflammation, inadequate vascularization, and progressive disorganization of extracellular matrix (ECM) architecture, which collectively disrupt the coordinated cascade of tissue regeneration. Mesenchymal stem cell (MSC)-derived exosomes have emerged as a potent cell-free therapeutic approach capable of addressing these pathological barriers through multi-level biological modulation of immune, vascular, and stromal compartments. Preclinical studies demonstrate that topical or injectable administration of MSC-derived exosomes accelerates wound closure by 25–60% within 10–14 days compared to controls. Immunomodulatory effects include promoting macrophage polarization from M1 to M2 phenotypes, with reported increases in M2/M1 ratios of 1.5–3.2-fold, mediated by exosomal miRNAs (e.g., miR-223, miR-181c) and proteins that suppress NF-κB signaling. Angiogenesis is markedly enhanced, with microvascular density rising by 30–70%, driven by the transfer of VEGF, miR-126, and miR-21 to endothelial cells, thereby boosting migration and tube formation. Fibroblast activity is similarly upregulated, resulting in 1.4–2.0-fold increases in collagen deposition and restoration of the MMP/TIMP balance, leading to improved tensile strength and ECM integrity. Integration of biomaterial-assisted delivery platforms, including thermosensitive hydrogels, collagen scaffolds, and microneedle arrays, extends exosome retention and functional bioavailability at the wound site by 2–5 times compared to free vesicles. While early clinical trials report safety and feasibility, challenges in large-scale GMP manufacturing, batch-to-batch consistency, and regulatory harmonization. Overcoming these translational barriers through advances in bioengineering, genetic modification, and smart delivery systems may enable the evolution of MSC-derived exosomes into standardized, next-generation therapeutics for chronic, non-healing wounds.

Tumor metastasis is the primary cause of high mortality rates among cancer patients. Invasive tumor cells disseminate through the bloodstream as circulating tumor cells (CTCs) and subsequently colonize secondary organs. In addition to genetic mutations that govern biological processes, epigenetic alterations also regulate tumor cell gene expression and chromosome stability. Dysregulation of these patterns is pivotal to carcinogenesis, tumor progression, and metastasis. This narrative review initiates with a comprehensive overview of the biology of CTCs and the processes that contribute to epithelial-mesenchymal transition (EMT), immune surveillance, and colonization. Subsequently, the impact of epigenetic modifications in CTCs on these metastatic processes during CTC migration, survival, and dissemination will be examined. In addition, the paper presents the implications of targeting epigenetics in CTCs for cancer patients and introduces CTCs as new biomarkers for early detection, prognosis, and targeted therapies to improve patient outcomes. Graphical Abstract

Electrochemical sensor for malathion detection based on green g-C ₃ N ₄ @LiCoO ₂ nanocomposites.