Gelatin-based micro-hydrogel carrying genetically engineered human endothelial cells for neovascularization

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Cell delivery systems are crucial for therapeutic angiogenesis and long-term cell survival in transplantation.
• Micro-hydrogels offer a promising scaffold for supporting cell proliferation, attachment, and migration in ischemic conditions.

Purpose of the Study:

• To fabricate a gelatin methacrylate (GelMA)-based micro-hydrogel for efficient in vivo delivery of genetically engineered endothelial cells.
• To evaluate the efficacy of these micro-hydrogels in treating hindlimb ischemia by promoting neovascularization.

Main Methods:

• GelMA and alginate (ALG) mixtures were processed via electrospraying to form micro-hydrogels, followed by secondary crosslinking.
• Human umbilical vein endothelial cells (HUVECs) engineered to express vascular endothelial growth factor (VEGF) were seeded onto the micro-hydrogels.
• The fabricated micro-hydrogels with HUVECs were transplanted into a hindlimb ischemia mouse model.

Main Results:

• The GelMA micro-hydrogels supported the angiogenic response of HUVECs in a concentration-dependent manner.
• Transplantation of VEGF-secreting HUVEC-loaded GelMA micro-hydrogels effectively attenuated hindlimb ischemia.
• Restoration of blood flow and significant neovascularization were observed in the treated mice.

Conclusions:

• The developed GelMA micro-hydrogel fabrication strategy is a facile and robust method for creating efficient cell carriers.
• These ECM-based micro-hydrogels represent a novel platform for therapeutic neovascularization and tissue engineering applications.
• High-throughput fabrication of micro-hydrogels holds potential for treating various ischemic diseases.