Integrated Design of a Mussel‐Inspired Hydrogel Biofilm Composite Structure to Guide Bone Regeneration

Abstract Ideal biomedically engineered hydrogels should imitate the physiological environment of natural bone tissue healing. The healing ability of soft tissue is stronger than that of bone tissue, thus leading to premature growth of soft tissue into the bone tissue area of the defect and resulting in poor bone tissue healing at the defect site. In addition, good cellular affinity is necessary to allow for postimplantation fusion with surrounding tissues. Inspired by the adhesion mechanism of natural mussels, a polydopamine‐polyacrylamide (PDA‐PAM) single‐network hydrogel and a PDA‐PAM/ACP hydrogel composed of amorphous hydroxyapatite (ACP) is designed to maintain sufficient free catechol groups in the hydrogel by preventing excessive oxidation of dopamine. The hydrogels are found to confer a strong healing ability without stimulation and to have cellular affinity. More notably, separation of the ACP layer and PDA‐PAM hydrogel is not easy to achieve in a synthetic hydrogel. It is found that the hydrogels (PDA‐PAM/ACP) promote bone formation. The gel up‐regulates the expression of osteogenic genes including alkaline phosphatase, runt‐related transcription factor 2, and osteocalcin. In vivo, 8‰ PDA‐PAM/ACP gel is found to effectively repair skull defects.