In Situ Bioprinting Embryonic-Derived Stem Cells to Repair Human Ex Vivo Chondral Defects

Area of Science:

• Regenerative Medicine
• Biotechnology
• Tissue Engineering

Background:

• Cartilage defects, particularly in osteoarthritic (OA) joints, present significant clinical challenges.
• Current treatments for cartilage regeneration are limited, necessitating innovative approaches.
• In situ bioprinting offers a promising strategy for direct tissue repair within defects.

Purpose of the Study:

• To evaluate the feasibility of in situ bioprinting for regenerating cartilage lesions.
• To assess the combination of embryonic-derived mesenchymal stem cells (ES-MSCs) with fibrin-based bioinks for neocartilage formation.
• To utilize an integrated bioprinting platform for precise delivery into chondral defects in human OA tissue.

Main Methods:

• Employed a 6-axis bioprinting system with laser scanning to map and fill chondral defects.
• Encapsulated ES-MSCs in fibrinogen-based bioinks modified with nanocellulose and/or hyaluronic acid.
• Bioprinted constructs in vitro and ex vivo, followed by cross-linking and 8-week chondrogenic culture.

Main Results:

• Incorporating nanocellulose into fibrinogen bioinks significantly enhanced print fidelity.
• Bioprinted ES-MSCs generated cartilage-like neotissues, confirmed by Safranin O and collagen type II staining.
• Constructs showed upregulated chondrogenic gene expression and increased mechanical properties (up to ~150 kPa) over 8 weeks.

Conclusions:

• Demonstrated the feasibility of in situ bioprinting for neocartilage generation in human OA tissue.
• Validated the use of ES-MSCs within printable fibrin-based hydrogels for cartilage repair.
• The integrated bioprinting approach shows potential for effective treatment of chondral defects.