Abstract

This work describes the development of an injectable nanocomposite system based on a chitosan thermosensitive hydrogel combined with liposomes for regenerative medicine applications. Liposomes with good physicochemical properties are prepared and embedded within the chitosan network. The resulting nanocomposite hydrogel is able to provide a controlled release of the content from liposomes, which are able to interact with cells and be internalized. The cellular uptake is enhanced by the presence of a chitosan coating, and cells incubated with liposomes embedded within thermosensitive hydrogels displayed a higher cell uptake compared to cells incubated with liposomes alone. Furthermore, the gelation temperature of the system resulted to be equal to 32.6 °C; thus, the system can be easily injected in the target site to form a hydrogel at physiological temperature. Given the peculiar performance of the selected systems, the resulting thermosensitive hydrogels are a versatile platform and display potential applications as controlled delivery systems of liposomes for tissue regeneration.

Highlights

  • IntroductionLiposomes are nanocarriers made of single units that can self-assemble, driven by soft interactions

  • Accepted: 12 January 2022Liposomes are nanocarriers made of single units that can self-assemble, driven by soft interactions

  • Considering all the benefits offered by the resulting system, we propose the use of these hydrogels as a versatile platform that can be translated into the controlled release of extracellular vesicles (EVs), and they can be used as innovative translational biomaterials in the field of regenerative medicine

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Summary

Introduction

Liposomes are nanocarriers made of single units that can self-assemble, driven by soft interactions. Like cell membranes, they can be composed mainly of phospholipids and cholesterol (Figure 1). Phospholipids are amphiphilic macromolecules that exhibit both hydrophobic and hydrophilic behavior; once in contact with water, they tend to aggregate, forming lipid bilayer nanocarriers [1]. Liposomes have some interesting advantages: they are easy to prepare, versatile, highly biocompatible, and biodegradable [2,3]. They can be loaded with biologically active compounds that can be conveyed to a desired target. The cell–liposome interaction depends on liposomes’ physiochemical features such as size, shape, hydrophobicity, and surface charge. Neutral and negatively charged particles display poor cell interaction, whereas positively charged liposomes usually show enhanced cell interaction [3,4]

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