Near-infrared controlled release of mesenchymal stem cells secretome from bioprinted graphenebased microbeads for nerve regeneration

Nerve damage is a prevalent and debilitating condition with limited treatment options. Recent years have seen an increased incidence of neural damage due to factors such as aging populations and traumatic brain injuries. Addressing the urgent need for effective therapies, this study explores the controlled delivery of mesenchymal stem cells (MSCs) secretome, a complex mixture of bioactive factors, which is currently being investigated for its potential in nerve regeneration. The secretome offers significant advantages over stem cells themselves, as it can be more easily characterized and controlled, enabling precise regulation of therapeutic interventions. However, the challenge lies in delivering the secretome specifically to the target anatomical region. To overcome this limitation, we propose a novel approach utilizing near-infrared (NIR) radiation-responsive bioprinted alginate-graphene oxide (AGO) microbeads. Graphene oxide (GO) is a highly biocompatible material with unique properties, including NIR responsiveness, enabling controlled release of therapeutic agents upon NIR exposure. We hypothesized that AGO microbeads could encapsulate MSCs secretome and release it in a controlled manner using NIR radiation. To investigate our hypothesis, controlled damage was induced to hippocampal neurons, and MSCs secretome was encapsulated within AGO microbeads. Subsequently, NIR radiation was applied to trigger the release of the secretome. We compared the efficacy of MSCs secretome with that of astrocytes, which also possess nerve growth and proliferation-promoting capabilities. Our findings demonstrated that the controlled release of MSCs secretome from AGO microbeads through non-invasive NIR radiation significantly promoted the proliferation and regeneration of neurons following nerve injury. AGO microbeads offer multiple advantages over conventional delivery methods, including precise control over the timing, location, and dosage of therapeutic agents. Furthermore, the potential for reduced immunogenicity and tumorigenicity enhances the safety profile of the therapy. Consequently, this study presents a promising avenue for the development of MSC-based therapies for nerve regeneration, with implications for the treatment of various neuropathies and injuries.