Revolutionizing dermatology: harnessing mesenchymal stem/stromal cells and exosomes in 3D platform for skin regeneration.

Contemporary trends reveal an escalating interest in regenerative medicine-based interventions for addressing refractory skin defects. Conventional wound healing treatments, characterized by high costs and limited efficacy, necessitate a more efficient therapeutic paradigm to alleviate the economic and psychological burdens associated with chronic wounds. Mesenchymal stem/stromal cells (MSCs) constitute cell-based therapies, whereas cell-free approaches predominantly involve the utilization of MSC-derived extracellular vesicles or exosomes, both purportedly safe and effective. Exploiting the impact of MSCs by paracrine signaling, exosomes have emerged as a novel avenue capable of positively impacting wound healing and skin regeneration. MSC-exosomes confer several advantages, including the facilitation of angiogenesis, augmentation of cell proliferation, elevation of collagen production, and enhancement of tissue regenerative capacity. Despite these merits, challenges persist in clinical applications due to issues such as poor targeting and facile removal of MSC-derived exosomes from skin wounds. Addressing these concerns, a three-dimensional (3D) platform has been implemented to emend exosomes, allowing for elevated levels, and constructing more stable granules possessing distinct therapeutic capabilities. Incorporating biomaterials to encapsulate MSC-exosomes emerges as a favorable approach, concentrating doses, achieving intended therapeutic effectiveness, and ensuring continual release. While the therapeutic potential of MSC-exosomes in skin repair is broadly recognized, their application with 3D biomaterial scenarios remains underexplored. This review synthesizes the therapeutic purposes of MSCs and exosomes in 3D for the skin restoration, underscoring their promising role in diverse dermatological conditions. Further research may establish MSCs and their exosomes in 3D as a viable therapeutic option for various skin conditions.