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International Journal of Bioprinting NIR-secretome release for nerve regeneration

of MSCs secretome, importantly, a significantly strong to the easy and repeatable production of alginate and GO,
recover of cell viability was observed in neural cells, which along with the easy storage and stability, future large-scale
reached 76% ± 1.8% (Figure 4D, p < 0.05, one-way ANOVA production of these AGO particles will be achievable. These
and Tukey’s post-hoc test). The production of ROS was also advantages make AGO microbeads a promising platform
monitored after neural damage and NIR irradiation. The for the development of MSC-based therapies for neuronal
release of culture medium mildly affected the production recovery after injury. This innovative approach holds
of free radicals, reducing the levels from 206% ± 28.4% of great potential for the treatment of various neuropathies
the positive control down to 180% ± 23.6% (Figure 4E, and injuries, offering new possibilities for enhancing
p < 0.05, one-way ANOVA and Tukey’s post-hoc test). The patient outcomes and quality of life. Further research is
release of ACM after NIR had an even stronger effect on warranted to explore the underlying mechanisms of action
ROS of neural cells, reducing their production to 160% ± and optimize the parameters of NIR-responsive delivery
29.5% (Figure 4F, p < 0.05, one-way ANOVA and Tukey’s systems. Future studies regarding the biodistribution of
post-hoc test). Finally, the release of MSCs secretome had microbeads after local injection will have to be performed.
the strongest effect even on the production of ROS, which The development of robust and safe MSC-based therapies
was significantly reduced to 126% ± 3.4% (Figure 4G, utilizing the controlled delivery of the secretome holds
p < 0.01, one-way ANOVA and Tukey’s post-hoc test). promise for addressing the unmet clinical needs in
Calcein staining furtherly confirmed viability and neuronal regeneration and providing effective treatments
ROS production data, indicating a significantly higher for patients with neurological disorders and injuries.
cell proliferation in neural cells after recovery with MSCs Acknowledgments
secretome with respect to the other treatments (Figure 5A
and B). Our findings demonstrate that the secretome of None.
MSCs holds immense regenerative potential for nerve
repair. Its controlled release from AGO microbeads Funding
showcases superior efficacy in enhancing cell viability Not applicable.
and reducing ROS production in damaged neural cells,
surpassing the effects observed with ACM and standard Conflict of interest
culture medium. These findings offer promising insights
into the therapeutic applications of MSC secretome in The authors declare no conflict of interest.
nerve regeneration, highlighting its significance in future
research and clinical interventions. Author contributions
4. Conclusion Conceptualization: Massimiliano Papi, Marco De Spirito
Formal analysis: Giordano Perini
Our study presents a novel approach for the controlled Investigation: Giordano Perini, Valentina Palmieri,
delivery of MSCs secretome for neuronal regeneration Marcello D’Ascenzo, Claudia Colussi
using NIR-responsive bioprinted AGO microbeads. By Methodology: Ginevra Friggeri, Alberto Augello, Lishan
encapsulating the MSCs’ secretome in AGO microbeads Cui
and utilizing NIR radiation, we successfully achieved the Writing – original draft: Giordano Perini
controlled release of therapeutic factors for promoting Writing – review & editing: Massimiliano Papi, Claudio
neuronal proliferation, survival, and viability. Our findings Grassi, Marco De Spirito
highlight the efficacy of the MSCs secretome in promoting
neural proliferation compared to the secretome derived Ethics approval and consent to participate
from astrocytes, a known promoter of nerve regeneration. Animal procedures (E18 isolation and neuronal cultures)
The controlled release of the MSCs secretome through were approved by the Ethical Committee of the Università
non-invasive NIR radiation from AGO microbeads Cattolica del Sacro Cuore (authorization n° 494/2022-
demonstrated significant benefits in terms of neuronal PR) and were fully compliant with Italian (Ministry of
proliferation and regeneration following induced toxicity. Health guidelines, Legislative Decree No. 116/1992) and
This approach offers advantages over conventional European Union (Directive No. 86/609/EEC) legislations
delivery methods, such as precise control over the timing, on animal research.
location, and dosage of therapeutic agents. The use of AGO
microbeads not only allows for controlled release but also Consent for publication
provides additional benefits, including potential reductions
in immunogenicity and tumorigenicity. Furthermore, due Not applicable.

Volume 10 Issue 1 (2024) 238 https://doi.org/10.36922/ijb.1045