Membrane Wrapping Pathway of Injectable Hydrogels: From Vertical Capillary Adhesion to Lateral Compressed Wrapping.

Membrane wrapping pathway of injectable hydrogels (IHs) plays a vital role in the nanocarrier effectiveness and biomedical safety. Although considerable progress in understanding this complicated process has been made, the mechanism behind this process has remained elusive. Herein, with the help of large-scale dissipative particle dynamics simulations, we explore the molecular mechanism of membrane wrapping by systematically examining the IH architectures and hydrogel-lipid binding strengths. To the best of our knowledge, this is the first report on the membrane wrapping pathway on which IHs transform from vertical capillary adhesion to lateral compressed wrapping. This transformation results from the elastocapillary deformation of networked gels and nanoscale confinement of the bilayer membrane, and it takes long time for the IHs to be fully wrapped owing to the high energy barriers and wrapping-induced shape deformation. Collapsed morphologies and small compressed angles are identified in the IH capsules with a thick shell or strong binding strength to lipids. In addition, the IHs binding intensively to the membrane exhibit special nanoscale mixing and favorable deformability during the wrapping process. Our study provides a detailed mechanistic understanding of the influence of architecture and binding strength on the IH membrane wrapping efficiency. This work may serve as rational guidance for the design and fabrication of IH-based drug carriers and tissue engineering.