Synergistic, shape-controlled endothelialized spheroid-hydrogel for wound healing

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Full-thickness skin defects require advanced skin substitutes with biomimetic properties for effective healing.
• Vascularized spheroids are promising building blocks for functional tissue repair constructs.
• Current spheroid biofabrication methods suffer from low throughput, poor uniformity, and limited control.

Purpose of the Study:

• To develop a novel biomanufacturing method and an integrated platform for shape-controlled spheroid fabrication and assembly.
• To address limitations in spheroid uniformity, controllability, and spatial arrangement for vascularized construct biomanufacturing.
• To establish an integrated technical framework for spheroid fabrication, culture, assembly, and in vivo application.

Main Methods:

• Developed a one-stop bioprinting platform for spheroids (OBPS) with real-time monitoring.
• Fabricated endothelialized spheroids via co-culture of human fibroblasts and human umbilical vein endothelial cells.
• Bioprinted spheroids and fibrinogen-supplemented gelatin methacryloyl hydrogel in situ onto full-thickness skin defects in nude mice.

Main Results:

• Shape-controlled endothelialized spheroids significantly accelerated wound closure in animal models.
• The bioprinted constructs suppressed inflammation and promoted neovascularization and collagen remodeling.
• Demonstrated excellent tissue integration and repair potential of the engineered spheroids.

Conclusions:

• The OBPS system provides a novel and effective approach for wound healing applications.
• This integrated biomanufacturing strategy enhances the potential of spheroids in tissue repair.
• The developed method offers improved control and efficiency in fabricating vascularized constructs for regenerative medicine.