Construction of Zn²⁺ Chelated Dodecapeptide Assembled Hydrogel with Bio-Adhesive and Bone Regeneration Functions

Hydrogels constructed from peptide components often rely on β-sheet architectures for their assembly, yet the process of developing such materials in aqueous environments presents notable hurdles in the context of biological systems. To address this, a novel functional dodecapeptide has been developed, capable of self-assembling into supra-molecular hydrogels via zinc chelation interactions. Morphological observations revealed a compact meshwork structure in the hydrogel formed with 9 mM Zn²⁺, differing from the relatively sparse or excessively tangled fiber architectures seen at other zinc concentrations. Alkaline phosphatase activity, an early marker of osteoblast differentiation, was notably enhanced when MC3T3-E1 cells were cultivated for 72 h in the hydrogel extract containing 300 μg/mL of the peptide, 9 μg/mL ZnCl₂, and 18.93 μg/mL H₃BO₃. Furthermore, increased protein levels of p-p38/p38, p-ERK/ERK, and p-JNK1/2/3/JNK1/2/3 were observed in P-300-ZnB and P-300 B hydrogel-treated groups, suggesting an association with MAPK pathway activation. P-Zn-9 hydrogel also promoted MC3T3-E1 cell proliferation and demonstrated favorable biocompatibility in short-term in vitro and in vivo assays. Long-term toxicity and causal relationships via inhibitor studies remain to be investigated. These results offer a viable approach to endow zinc-chelating properties in the fabrication of assembled hydrogels, presenting an innovative and potential method for constructing injectable drug delivery systems and in situ bone repair through biomaterials in subsequent applications.