Divalent Anion-Induced Biohydrogels with High Strength, Anti-swelling, and Bioactive Capability for Enhanced Skull Bone Regeneration

Increased intracranial pressure after traumatic braininjury (TBI)is an urgent problem in clinical practice. A pliable hydrogel is preferredfor cranioplasty applications after TBI since it can protect braintissue and promote bone healing. Nevertheless, biohydrogels for cranialbone regeneration still face challenges of poor mechanical properties,large swelling ratios, and low osteogenesis activity. Herein, inspiredby Hofmeister effects, biopolymer hydrogels composed of protein andpolysaccharides were treated with a Hofmeister series including aseries of monovalent and divalent anions. Our results reveal thatthe divalent anion-cross-linked biohydrogels exhibit stronger mechanicalproperties and lower swelling ratios compared with monovalent-aniontreated gels. Intriguingly, the divalent HPO4 (2-) anion induced biohybrid hydrogels with excellent mechanical behaviors(3.7 & PLUSMN; 0.58 MPa, 484 & PLUSMN; 76.7 kPa, and 148.3 & PLUSMN; 6.85 kJ/m(3)), anti-swelling capability (16.7%), and gradual degradationability, significantly stimulating osteogenic differentiation andin vivo cranial bone regeneration. Overall, this study may providenew insights into the design of biomimetic hydrogels for treatingcranial bone defects after TBI.