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3D-Printed Perfusable Lab-on-a-Chip-Based Engineering of MSC-Derived Exosome-Enriched Vascularized Grafts for Skin
Shalini Dasgupta1, Jaideep Adhikari2, Priyanka Das3
1Center for Healthcare Science and Technology, Indian Institute of Engineering Science and Technology, Shibpur, Howrah 711103, India.
ACS Applied Bio Materials
|July 11, 2025
Summary
This study developed an exosome-enriched bioink for 3D bioprinting functional vascular channels. The novel biomaterial promotes cell differentiation and vascular network formation, crucial for regenerative medicine applications like skin grafts.
Area of Science:
- Regenerative Medicine
- Biomaterials Science
- Tissue Engineering
Background:
- Vascularization is essential for engineered tissues but remains a significant challenge.
- Current strategies for vascularization often yield limited efficacy and compromised cell viability.
- Developing perfusable vascular networks is critical for the success of implanted tissue constructs.
Purpose of the Study:
- To develop an exosome-enriched biocomposite bioink for fabricating perfusable 3D vascular channels.
- To investigate the potential of this bioink in promoting vasculogenesis and endothelial cell differentiation.
- To establish a functional, biomimetic niche for vascularized tissue regeneration.
Main Methods:
- Fabrication of 3D vascular channel scaffolds using an exosome-enriched bioink (chitosan, collagen, fibrinogen, vitamin D3, and stem cell-derived exosomes) via extrusion bioprinting.
- Coculture of human adult dermal fibroblasts and dental pulp stem cells within a dynamic lab-on-a-chip system.
- Transcriptomic and proteomic analyses to evaluate endothelial transdifferentiation, angiogenic, and vasculogenic marker expression.
Main Results:
- The exosome-enriched bioink significantly enhanced endothelial transdifferentiation and vasculogenic activity compared to controls.
- Transcriptomic analysis revealed upregulation of key angiogenic and vasculogenic markers.
- Proteomic validation confirmed robust expression and organized localization of vascular development markers, indicating early vascular morphogenesis and lumen formation.
Conclusions:
- The developed exosome-enriched biocomposite bioink successfully created a functional, perfusable, and biomimetic 3D vasculogenic niche.
- This approach offers a promising strategy for fabricating vascularized skin grafts.
- The findings advance the translational potential of regenerative tissue constructs by addressing critical vascularization challenges.
