Adhesive liposomes loaded onto an injectable, self-healing and antibacterial hydrogel for promoting bone reconstruction

Abstract

Loading hydrogels with bioactive agents is an important method for expanding the functional application of hydrogels. However, how to improve the local administration and slow release of drugs from a hydrogel is a challenge when using hydrogels loaded with drugs. In this paper, we first developed adhesive liposomes (A-LIP) loaded with BMP-2. Then, we incorporated the A-LIP into PEG hydrogels based on the coordinated cross-linking principle of SH-PEG and Ag⁺, fabricating an injectable, antibacterial and self-healing multifunctional drug delivery system. The adhesive lipo-hydrogel (A-LIP-PEG) fabricated by mixing PEG hydrogels and adhesive liposomes can be locally injected into an osteoporotic fracture and bone marrow cavity, where A-LIP-PEG can release adhesive liposomes that adhere to the bone injury area and promote bone reconstruction. Based on the principle of electrostatic attraction, tissue nonspecific A-LIP were fabricated by grafting octadecylamine onto liposomes. Because of the coordination and cross-linking of thiolated polyethylene (SH-PEG) and Ag⁺, the A-LIP-PEG showed excellent injectability and self-healing properties; further, because of the presence of Ag⁺, the A-LIP-PEG showed effective inhibition of S. aureus and Escherichia coli. The liposomes released by the A-LIP-PEG were able to adhere to tissue. In vitro studies showed that A-LIP-PEG significantly promoted osteogenic differentiation and had no significant effect on cell proliferation. Compared with common lipo-hydrogel (LIP-PEG), the A-LIP-PEG had better tissue adhesion in vivo, which led to better osteogenic differentiation and faster local bone remodeling of osteoporotic fractures in rats. This research developed a novel hydrogel system with adhesive liposomes to expand the application of hydrogels.

Bone repair: Injectable hydrogels leave a lasting impression

Watery gels that fill cracks in fractured bones and release sticky bioagents to promote skeletal regrowth show promise in animal studies. Wenguo Cui from the Shanghai Jiao Tong University School of Medicine in China and colleagues have developed a spherical lipid vesicle or liposome that can encapsulate drugs, such as bone morphogenetic proteins, and slowly release them over time. The team modified the liposome’s structure to make it extra adhesive to tissue, and then mixed it into the porous structure of a hydrogel polymer containing antibacterial silver ions. The new material was fluid enough to be applied through a syringe, but remained firm once in place thanks to the gel’s network of self-healing bonds. X-ray analysis revealed that after 8 weeks, the gel had significantly improved bone mineralization in rat fractured femurs compared to controls.