Biodegradable High-Strength Hydrogels with Injectable Performance Based on Poly(l-Glutamic Acid) and Gellan Gum

Currently, biodegradable hydrogels are one of the most promising materials in tissue engineering. From the perspective of clinical needs, hydrogels with high strength and minimally invasive implantation are preferred for the reconstruction of load-bearing tissues. In this work, a biodegradable, high-strength, and injectable hydrogel was developed by one-step photo-cross-linking of two biomacromolecules, polyethylene glycol acrylated poly(l-glutamic acid) (PLGA-APEG) and methacrylated gellan gum (GG-MA). The hydrogels, named as PLGA/GG hydrogels, exhibited high mechanical properties. The compression stress of the hydrogels was 0.53 MPa, and the fracture energy was 7.7 ± 0.2 kJ m^-2. Meanwhile, the storage modulus could reach 44.0 ± 0.6 kPa. The hydrogel precursor solution loaded with adipose-derived stem cells (ASCs) was subcutaneously injected into C57BL/6 mice and then cross-linked via in situ transdermal irradiation, which demonstrated the excellent injectability and subcutaneous gelatinization of PLGA/GG hydrogels as cell carriers. Furthermore, three-dimensional encapsulation of ASCs in hydrogels after 7, 14, and 21 days showed outstanding cytocompatibility, and the viability of ASCs was up to 84.0 ± 1.7%. The PLGA/GG hydrogels exhibited ideal behaviors of degradation, with 60 ± 5% of hydrogels degraded in phosphate buffered solution (PBS) after 11 weeks. H&E staining demonstrated that the hydrogels degraded gradually after 6 weeks and supported tissue invasion without inflammatory reactions, which indicated the laudable biodegradability of hydrogels. Hence, the biodegradable and high-strength hydrogels with well-performed injectability and biocompatibility possessed high potential applications in tissue engineering, especially in load-bearing tissue regeneration.