Cartilage tissue engineering combining microspheroid building blocks and microneedle arrays

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Scaffold-free cartilage tissue engineering offers advantages over traditional methods by avoiding issues related to scaffold materials.
• Controlling the shape and integration of scaffold-free constructs remains a significant challenge in the field.
• Microneedle arrays present a potential solution for precise spatial arrangement of cellular building blocks.

Purpose of the Study:

• To investigate the feasibility of using microneedle arrays for bioprinting scaffold-free cartilage tissue constructs.
• To develop a method for assembling cellular microspheroids into predefined shapes using robotic systems and computer vision.
• To evaluate the potential of these constructs for repairing cartilage defects both ex vivo and in vivo.

Main Methods:

• Human embryonic-derived mesenchymal stem cells (hESC-MSCs) and infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) were used to form 500 µm microspheroids.
• A robotic system with computer vision guided the assembly of microspheroids onto microneedle arrays in specific patterns.
• Constructs were cultured for fusion and then tested in human osteoarthritic cartilage explants or implanted into rabbit osteochondral defects.

Main Results:

• Microspheroids from both cell types successfully fused to form neotissues with defined shapes and sizes.
• IPFP-MSC constructs expressed high levels of chondrogenic markers and integrated with host cartilage in explant models.
• hESC-MSC constructs showed in vivo chondrogenesis by 2 weeks and mature cartilage regeneration with increased glycosaminoglycan deposition by 8 weeks in rabbit models.

Conclusions:

• Defined scaffold-free cartilage shapes can be constructed using bioprinting and fusion of cellular microspheroids.
• The microneedle array approach provides a viable method for creating precise scaffold-free cartilage constructs.
• This technology shows promise for the repair of osteoarthritic cartilage defects both ex vivo and in vivo.