Hierarchically hollow microcapsules with antibacterial and angiogenic properties for abdominal wall defects treatment

Abstract

The utilization of mesh materials to repair abdominal wall defects (AWDs) is one of the most common operations in the surgical field. However, the repair efficiency for biological meshes is restricted by poor neovascularization and limited abilities to prevent bacterial contamination. To address these issues, we design a new type of hierarchically hollow microcapsules (HHMs) by microfluidics. The hollow mesoporous silica nanoparticles filled in the aqueous core of HHMs form the first hollow structure, while the polymer shell of HHMs with tailorable thickness forms the second hollow structure. Under the precise emulsification process of microfluidics, HHMs have a high monodispersity with the coefficient of variation value about 1.9%. Taking advantages of the hierarchically hollow structure, the resultant microcapsules can store large amounts of angiogenic molecules, and deliver these cargos in a controlled manner. In vitro experiments find that the bioactivities of angiogenic molecules are well preserved after microencapsulation and promote the capillary tube formation of endothelial cells. In addition, silver nanoparticles (AgNPs) are incorporated into the HHMs shell to provide antibacterial properties for these microcapsules. When AgNPs concentration set to 0.4‰, the colony counting is reduced by 99.8% for Gram-negative bacteria and 94.8% for Gram-positive bacteria, while the proliferation activity of normal cells remains more than 80.0%. In vivo experiments find that HHMs can facilitate the new blood vessel formation, restrain the bacteria adhesion, and decrease the inflammatory response after implantation into a rat model with AWDs. These unique characteristics of HHMs thus create a healthy environment for biological meshes to induce the regeneration of AWDs, accompanied by collagen deposition and granulation formation. Collectively, the proposed HHMs are promising devices in the application of defected tissue repair.