High-stiffness, fast-crosslinking, cartilage matrix bioinks.

Current approaches to cartilage regeneration face limitations in scaffold mechanics and surgical delivery. While devitalized cartilage particles have been used to create scaffolds, these often lack the mechanical performance of native cartilage. Additionally, the slow crosslinking of methacryloyl-modified cartilage bioinks hinders clinical translation. Prior research has shown that injectable bioinks with rapid crosslinking could improve surgical handling and retention. However, no prior work had resolved the challenge of achieving both high stiffness and fast crosslinking in cartilage-derived bioinks. This gap motivated the development of a new bioink using thiol-ene click chemistry. The need for a material that mimics native cartilage stiffness while enabling rapid in situ crosslinking remained unmet. Researchers have explored various modifications to cartilage matrix, but none have achieved the mechanical and processing properties needed for clinical use. This paper introduces a novel approach that addresses these limitations.

The study aimed to develop a cartilage-derived bioink with high mechanical performance and rapid crosslinking. The specific problem addressed was the slow crosslinking time of methacryloyl-modified cartilage bioinks, which limits their clinical utility. The motivation stemmed from the need for a material that could be injected and crosslinked in situ within a short timeframe. The goal was to enable surgical placement and retention of the scaffold within any defect shape. The researchers sought to improve the mechanical properties of cartilage scaffolds while maintaining ease of delivery. A key objective was to test the effect of pentenoate modification on crosslinking speed and mechanical performance. The study also aimed to evaluate the impact of adding devitalized cartilage particles on printability and cell viability. By addressing these factors, the researchers hoped to advance the translational potential of cartilage matrix bioinks.

The researchers fabricated a pentenoate-modified solubilized devitalized cartilage (PSDVC) using thiol-ene click chemistry. This modification was designed to accelerate the crosslinking process compared to methacryloyl-modified cartilage (MeSDVC). The crosslinking times of PSDVC and MeSDVC were compared using a photoinitiator. The solid and fluid mechanics of the bioinks were characterized using rheological and compressive modulus tests. The researchers also evaluated the printability of the bioinks by assessing shape fidelity and clogging during extrusion. A pentenoate-modified hyaluronic acid (PHA) was used as a control to compare mechanical and printing properties. The effects of adding devitalized cartilage particles to PHA or PSDVC were also analyzed. The study combined material synthesis, mechanical testing, and bioprinting trials to evaluate the performance of the new bioink.

The PSDVC bioink demonstrated a significantly faster crosslinking time of approximately 1.7 minutes, compared to 4 minutes for MeSDVC. The compressive modulus of the crosslinked PSDVC was 3.12 ± 0.41 MPa, which is closer to native cartilage stiffness than other tested materials. The paste-like rheology of PSDVC before crosslinking allowed for good bioprintability and shape fidelity. The addition of devitalized cartilage particles improved the printed shape fidelity of PHA and PSDVC. However, the inclusion of DVC particles increased clogging during printing and reduced cell viability after bioprinting. The PHA bioink showed lower mechanical performance than PSDVC, highlighting the advantage of pentenoate modification. The study found that the fastest crosslinking and highest mechanical performance were achieved with PSDVC alone. These results suggest that PSDVC has potential for clinical translation due to its rapid crosslinking and high stiffness.

The authors propose that the PSDVC bioink may have translational potential for cartilage repair due to its rapid crosslinking and high mechanical performance. The study suggests that the thiol-ene modification enables faster in situ crosslinking than methacryloyl modification. The researchers observed that the compressive modulus of PSDVC after crosslinking was among the highest reported for cartilage-derived bioinks. The study also indicates that the paste-like rheology of PSDVC facilitates surgical delivery and retention. The addition of devitalized cartilage particles improved shape fidelity but reduced printability and cell viability. The findings suggest that further refinement is needed for DVC-containing bioinks to improve their clinical suitability. The authors conclude that the PSDVC alone offers the best combination of mechanical and processing properties for cartilage regeneration. These results support the potential of pentenoate-modified cartilage bioinks for future clinical applications.