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 crosslinking 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.

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

“…The system could be used for the treatment of bone cavity damage and reduces the risk of postoperative infections. The presence of silver ions in the adhesive liposome PEG gel system showed effective inhibition of S. aureus and E. coli pathogens [73].…”

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“…This system showed good potential for the repair of the local damaged bone cavity. [ 126 ] However, the A‐LIP released by A‐LIPPEG markedly increased the relative fluorescence intensity (100 ± 20%) as an indicator of osteocalcin (OCN) expression (green), whereas LIP‐PEG and control groups exhibited very weaker fluorescence intensity (46 ± 8%, and 4 ± 1%, respectively), indicating high potential of A‐LIPPEG for enhancement of the osteogenic differentiation of BMSCs (Figure 9F). The assessment of bone healing by micro‐CT scans demonstrated that mineralization and the healing of the fracture in the A‐LIP‐PEG treatment group were greater than the control and LIP‐PEG groups (Figure 9G).…”

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“…Staphylococcus aureus bacteria as a mouse model of skin infection Release of carboxyl-modified gold nanoparticles onto mouse skin [ 210] Adhesive cationic liposomes containing lecithin, cholesterol, and octadecylamine Ag + loaded thiolated polyethylene hydrogels Liposomes (A-LIP) loaded with bone morphogenetic protein 2 Local bone remodeling of osteoporotic fractures in rats [ 211] Polymersomes of the triblock copolymer PNAM-b-PChA-b-PNAM PVA hydrogel matrix C2C12 mouse myoblast cell line Release of the small cytotoxic depsipeptide drug thiocoraline [ 272] Polymersomes of the triblock copolymer PMOXA-b-PDMS-b-PMOXA…”

“…[210] This preparation sustained nanoparticle release within 24 h, without producing any toxic effect on the mouse skin within a 7-day treatment. Another recent demonstration of antibacterial applications is provided by the recent example of Liu et al, [211] who loaded octadecylamine grafted liposomes into Ag + loaded thiolated polyethylene hydrogels, obtaining an interesting system, which combines good self-healing with excellent antibacterial properties (tested on S. aureus and Escherichia coli) thanks to the presence of Ag + .…”