Dynamically Cross-Linked Granular Hydrogels for 3D Printing and Therapeutic Delivery

• Published in: ACS applied bio materials 2023-09, Vol.6 (9), p.3683-3695
• Main Authors: Lee, Hung-Pang, Davis, Ryan, Wang, Ting-Ching, Deo, Kaivalya A., Cai, Kathy Xiao, Alge, Daniel L., Lele, Tanmay P., Gaharwar, Akhilesh K.
• Format: Article
• Language: English
• Subjects: Biocompatible Materials - chemistry; Hydrogels - chemistry; Microgels; Printing, Three-Dimensional; Tissue Engineering - methods
• ISSN: 2576-6422; 2576-6422
• DOI: 10.1021/acsabm.3c00337

Granular hydrogels have recently emerged as promising biomaterials for tissue engineering and 3D-printing applications, addressing the limitations of bulk hydrogels while exhibiting desirable properties such as injectability and high porosity. However, their structural stability can be improved with post-injection interparticle cross-linking. In this study, we developed granular hydrogels with interparticle cross-linking through reversible and dynamic covalent bonds. We fragmented photo-cross-linked bulk hydrogels to produce aldehyde or hydrazide-functionalized microgels using chondroitin sulfate. Mixing these microgels facilitated interparticle cross-linking through reversible hydrazone bonds, providing shear-thinning and self-healing properties for injectability and 3D printing. The resulting granular hydrogels displayed high mechanical stability without the need for secondary cross-linking. Furthermore, the porosity and sustained release of growth factors from these hydrogels synergistically enhanced cell recruitment. Our study highlights the potential of reversible interparticle cross-linking for designing injectable and 3D printable therapeutic delivery scaffolds using granular hydrogels. Overall, our study highlights the potential of reversible interparticle cross-linking to improve the structural stability of granular hydrogels, making them an effective biomaterial for use in tissue engineering and 3D-printing applications.