Abstract
Hyaluronic acid (HA) is a natural, linear, endogenous polysaccharide that plays important physiological and biological roles in the human body. Nowadays, among biopolymers, HA is emerging as an appealing starting material for hydrogels design due to its biocompatibility, native biofunctionality, biodegradability, non-immunogenicity, and versatility. Since HA is not able to form gels alone, chemical modifications, covalent crosslinking, and gelling agents are always needed in order to obtain HA-based hydrogels. Therefore, in the last decade, different strategies for the design of physical and chemical HA hydrogels have been developed, such as click chemistry reactions, enzymatic and disulfide crosslinking, supramolecular assembly via inclusion complexation, and so on. HA-based hydrogels turn out to be versatile platforms, ranging from static to smart and stimuli-responsive systems, and for these reasons, they are widely investigated for biomedical applications like drug delivery, tissue engineering, regenerative medicine, cell therapy, and diagnostics. Furthermore, the overexpression of HA receptors on various tumor cells makes these platforms promising drug delivery systems for targeted cancer therapy. The aim of the present review is to highlight and discuss recent advances made in the last years on the design of chemical and physical HA-based hydrogels and their application for biomedical purposes, in particular, drug delivery. Notable attention is given to HA hydrogel-based drug delivery systems for targeted therapy of cancer and osteoarthritis.
Highlights
Hydrogels are three-dimensional, hydrated polymeric networks, formed by crosslinked hydrophilic polymers with a high affinity for water and biological fluids, capable of absorbing from 10% up to thousands of times their dry weight in water [1]. Thanks to their unique properties such as biocompatibility, biodegradability, flexibility, softness, etc., hydrogels have been widely investigated for biomedical applications like cell therapy, tissue engineering, drug delivery, and diagnostics [2]
Hydrogels made of pectin, carboxymethylcellulose and propylene glycol or polyethylene glycol (PEG) and propylene glycol are used as wound dressings [3,4], keratin- or polyvinyl alcohol-based hydrogels as scaffolds for cell growth [5,6], PEG-based hydrogel (DEXTENZA®), recently approved by the Food and Drug Administration, as ophthalmic inserts, etc. [7]
Hyaluronic acid (HA) represents one of the most used in the design of hydrogels for biomedical applications due to its biocompatibility, native biofunctionality, biodegradability, non-immunogenicity, and versatility
Summary
Hydrogels are three-dimensional, hydrated polymeric networks, formed by crosslinked hydrophilic polymers with a high affinity for water and biological fluids, capable of absorbing from 10% up to thousands of times their dry weight in water [1]. In the extracellular matrix of most tissues it contributes to maintain the tissue’s mechanical integrity, homeostasis, viscoelasticity and lubrication thanks to its high molecular weight and its capacity to absorb a high quantity of water [12] It plays an important role in intracellular functions; it is able to regulate, due to its binding to cell surface specific receptors (such as CD44 or RHAMM), cell adhesion, migration, proliferation, and differentiation and, processes like inflammation, wound healing, tissue development, morphogenesis, tumor progression, and metastasis [13]. The aim of the present review is to highlight and discuss recent advances made in the last years on the design of chemical and physical HA-based hydrogels and their application for biomedical purposes, in particular, drug delivery
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