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 tong 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-mateimide 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 degrees 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.