可注射的 Diels-Alder 环加成水凝胶，具有可调节的凝胶化、刚度和降解性能，用于 T 淋巴细胞的持续释放

Engineered T-cell therapies have proven highly efficacious for the treatment of haematological cancers, but translation of this success to solid tumours has been limited, in part, due to difficulties in maintaining high doses at specific target sites. Hydrogel delivery systems that provide a sustained release of T-cells at the target site are emerging as a promising strategy.

Therefore, in this study we aimed to develop an injectable hydrogel that gels in situ via efficient Diels-Alder cycloaddition (DAC) chemistry and provides a sustained release of T-cells through gradual hydrolysis of the hydrogel matrix. Hydrogels were prepared via the DAC between fulvene and maleimide functionalised poly(ethylene glycol) (PEG) derivatives. By adjusting the concentration and molecular weight of the functionalised PEGs in the hydrogel formulation the in vitro gelation time ( T gel ), initial Young's modulus ( E ) and degradation time ( T d ) could be tailored from 15-150 min, 5-179 kPa and 7-114 h, respectively.

Prior to gelation, the formulations could be readily injected through narrow gauge (26 G) needles with the working time correlating closely with the T gel . A 5 wt% hydrogel formation with conjugated cyclic RGD motif was found to be optimal for the encapsulation and release of CD3 + T-cells with a near linear release profile and >70% cell viability over the first 4 d and release continuing out to 7 d. With their tuneable T gel , T d and stiffness, the DAC hydrogels provide the opportunity to control the release period and profile of encapsulated cells.