Diels-Alder crosslinked HA/PEG hydrogels with high elasticity and fatigue resistance for cell encapsulation and articular cartilage tissue repair

The rapid restoration or regeneration of cartilage tissue biomechanical function remains a challenge, especially the replication of structural and mechanical properties using novel scaffold designs. A new class of cross-linked hydrogels with significantly improved mechanical properties has been synthesized by the Diels-Alder (DA) click reaction, which is widely used in drug delivery, sensor technology, and tissue engineering. However, the long gelation time of DA formed hydrogel is a big obstacle for cell encapsulation and restricts its application in the cytobiology field. In this research, a novel biological hydrogel was synthesized from hyaluronic acid (HA) and PEG by DA "click" chemistry. By simply tuning the furyl-to-maleimide molar ratio and the substitution degree of the furyl group, the value of the compressive modulus was controlled from 4.86 ± 0.42 kPa to 75.90 ± 5.43 kPa and the gelation time could be tuned from 412 min to 51 min at 37 °C. Moreover, the DA formed hydrogel was utilized to investigate the cell encapsulation viability and the influence of gelation time on encapsulated cell survival, and the results showed that a gelation time of about 1 h was suitable for cell viability, proliferation and chondrogenesis. Meanwhile, the HA/PEG hydrogel showed outstanding load-bearing and shape recovery properties even after 2000 loading cycles, mimicking the mechanical properties and behavior of articular cartilage. Therefore, the DA crosslinked HA/PEG hydrogel, with good mechanical properties and short gelation time, has significant potential applications in cartilage tissue engineering. This journal is