Abstract
Hyaluronic acid (HA) is a natural polyelectrolyte abundant in mammalian connective tissues, such as cartilage and skin. Both endogenous and exogenous HA produced by fermentation have similar physicochemical, rheological, and biological properties, leading to medical and dermo-cosmetic products. Chemical modifications such as cross-linking or conjugation in target groups of the HA molecule improve its properties and in vivo stability, expanding its applications. Currently, HA-based scaffolds and matrices are of great interest in tissue engineering and regenerative medicine. However, the partial oxidation of the proximal hydroxyl groups in HA to electrophilic aldehydes mediated by periodate is still rarely investigated. The introduced aldehyde groups in the HA backbone allow spontaneous cross-linking with adipic dihydrazide (ADH), thermosensitivity, and noncytotoxicity to the hydrogels, which are advantageous for medical applications. This review provides an overview of the physicochemical properties of HA and its usual chemical modifications to better understand oxi-HA/ADH hydrogels, their functional properties modulated by the oxidation degree and ADH concentration, and the current clinical research. Finally, it discusses the development of biomaterials based on oxi-HA/ADH as a novel approach in tissue engineering and regenerative medicine.
Highlights
Hyaluronic acid (HA) is a glycosaminoglycan comprising repeating disaccharide units of glucuronic acid and N-acetylglucosamine that is widely distributed in the extracellular matrix (ECM) and plays a vital role in vertebrate tissue morphogenesis [1]
This review focuses on the preparation and characterization of oxi-HA-based biomaterials, compares the properties and benefits of oxi-HA/adipic dihydrazide (ADH) regarding HA, presents clinical studies, and discusses the potential of oxi-HA/ADH-based biomaterials for tissue engineering and regenerative medicine
The structural changes and ADH cross-linking modulate functional properties, such as the gelation time, swelling, and stability of the oxi-HA/ADH hydrogels: the gelation time increases with increasing oxidation degree and ADH concentration; the moderate 65% oxidation degree and 4% ADH concentration produce the highest stability and least amount of swelling
Summary
Hyaluronic acid (HA) is a glycosaminoglycan comprising repeating disaccharide units of glucuronic acid and N-acetylglucosamine that is widely distributed in the extracellular matrix (ECM) and plays a vital role in vertebrate tissue morphogenesis [1]. The initial structural studies and evolution of analysis techniques boosted research on the macromolecular and physiological properties, followed by molecular recognition, cell biology, and HA metabolism These stages have extensive ramifications, and HA development from Balazs’ studies crowned HA for clinical applications [4]. Extensive studies of HA hydrogels have led to applications in tissue engineering and regenerative medicine [6,7], diagnostics [8], cell immobilization [9], separation of biomolecules or cells [10], and the regulation of biological adhesions as barrier materials [11] because of their desirable properties, such as adaptive chemistry, biodegradability, biocompatibility, viscoelasticity, and chondrogenic potential [12]. This review focuses on the preparation and characterization of oxi-HA-based biomaterials, compares the properties and benefits of oxi-HA/ADH regarding HA, presents clinical studies, and discusses the potential of oxi-HA/ADH-based biomaterials for tissue engineering and regenerative medicine
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