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.
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.
“…Polymeric hydrogels, a 3D hydrophilic polymer network, have been highlighted as an attractive candidate for 3D bioink materials owing to their structural and chemical similarity to the natural ECMs, simplicity of physicochemical modulation, and easy encapsulation of various therapeutic agents (i.e., drugs, genes, peptides, proteins, and cells). In particular, in situ cross-linkable hydrogels have been used extensively as bioinks, which show a sol-to-gel phase transition via various physical and chemical cross-linking reactions. − The target cells can be encapsulated easily within hydrogel matrices during in situ hydrogel formation. Although various in situ forming hydrogels have been developed as bioinks, the production of advanced bioink materials for precisely recapitulating ECM is still a challenge due to the complexity of native tissues and the delineation of intrinsic properties of laden cells.…”
Three-dimensional (3D) bioprinting has attracted considerable attention for producing 3D engineered cellular microenvironments that replicate complex and sophisticated native extracellular matrices (ECM) as well as the spatiotemporal gradients of numerous physicochemical and biological cues. Although various hydrogel-based bioinks have been reported, the development of advanced bioink materials that can reproduce the complexity of ECM accurately and mimic the intrinsic property of laden cells is still a challenge. This paper reports 3D printable bioinks composed of phenol-rich gelatin (GHPA) and graphene oxide (GO) as a component for a myogenesis-inducing material, which can form a hydrogel network in situ by a dual enzyme-mediated cross-linking reaction. The in situ curable GO/GHPA hydrogel can be utilized successfully as 3D-printable bioinks to provide suitable cellular microenvironments with facilitated myogenic differentiation of C2C12 skeletal myoblasts. Overall, we suggest that functional bioinks may be useful in muscle tissue engineering and regenerative medicine.
“…41 Thus, enzymolysis was selected as driving force to induce peptide bond breakage within hydrogel. 42 Figure 5(b) shows the degradation profiles of different hydrogels in PBS solution containing 6 μg/mL collagenase at 37°C. Though these kinds of hydrogels present distinct degradation behavior, they can completely degrade after 72 h, suggesting quick biodegradability of these hydrogels in human body.Figure 5.(a) Swelling ratios of various hydrogels in phosphate buffer solution (pH 7.4) at 37 °C, and (b) degradation behavior of different hydrogels.…”
In situ forming hydrogels with strong adhesive strength and antibacterial activity are of great interest to serve as tissue adhesive in fields like wound dressing and mass hemorrhage. In this study, hybrid hydrogel (GOHA) based on gelatin and oxidized hyaluronic acid was developed and endowed with excellent mechanical strength and tissue adhesion. According to our results, GOHA hydrogel exhibits a fast gelation time of around 60 s, robust compression strength of 223.43 ± 24.28 kPa, and strong adhesion of 14.33 ± 0.78 kPa to porcine skin, which is much higher than that of commercial fibrin glue (around 1.00 kPa). Meanwhile, through the loading of levofloxacin, obvious antibacterial activity can be obtained for wider applications. Notably, it would not compromise the hemocompatibility and cytocompatibility in vitro. In summary, this kind of hybrid hydrogel shows great potential as tissue adhesive in biomedical fields.
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