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 suchas aging populations and traumatic brain injuries. Addressing the urgent need foreffective therapies, this study explores the controlled delivery of mesenchymal stemcells (MSCs) secretome, a complex mixture of bioactive factors, which is currently beinginvestigated for its potential in nerve regeneration. The secretome offers significantadvantages over stem cells themselves, as it can be more easily characterized andcontrolled, enabling precise regulation of therapeutic interventions. However, thechallenge 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 agentsupon NIR exposure. We hypothesized that AGO microbeads could encapsulate MSCssecretome and release it in a controlled manner using NIR radiation. To investigateour hypothesis, controlled damage was induced to hippocampal neurons, andMSCs secretome was encapsulated within AGO microbeads. Subsequently, NIRradiation was applied to trigger the release of the secretome. We compared theefficacy of MSCs secretome with that of astrocytes, which also possess nerve growthand proliferation-promoting capabilities. Our findings demonstrated that thecontrolled release of MSCs secretome from AGO microbeads through non-invasiveNIR radiation significantly promoted the proliferation and regeneration of neuronsfollowing nerve injury. AGO microbeads offer multiple advantages over conventionaldelivery methods, including precise control over the timing, location, and dosageof therapeutic agents. Furthermore, the potential for reduced immunogenicity andtumorigenicity enhances the safety profile of the therapy. Consequently, this studypresents a promising avenue for the development of MSC-based therapies for nerveregeneration, with implications for the treatment of various neuropathies and injuries.