The self-crosslinking smart hyaluronic acid hydrogels as injectable three-dimensional scaffolds for cells culture

Abstract

Although the disulfide bond crosslinked hyaluronic acid hydrogels have been reported by many research groups, the major researches were focused on effectively forming hydrogels. However, few researchers paid attention to the potential significance of controlling the hydrogel formation and degradation, improving biocompatibility, reducing the toxicity of exogenous and providing convenience to the clinical operations later on. In this research, the novel controllable self-crosslinking smart hydrogels with in-situ gelation property was prepared by a single component, the thiolated hyaluronic acid derivative (HA-SH), and applied as a three-dimensional scaffold to mimic native extracellular matrix (ECM) for the culture of fibroblasts cells (L929) and chondrocytes. A series of HA-SH hydrogels were prepared depending on different degrees of thiol substitution (ranging from 10 to 60%) and molecule weights of HA (0.1, 0.3 and 1.0 MDa). The gelation time, swelling property and smart degradation behavior of HA-SH hydrogel were evaluated. The results showed that the gelation and degradation time of hydrogels could be controlled by adjusting the component of HA-SH polymers. The storage modulus of HA-SH hydrogels obtained by dynamic modulus analysis (DMA) could be up to 44.6 kPa. In addition, HA-SH hydrogels were investigated as a three-dimensional scaffold for the culture of fibroblasts cells (L929) and chondrocytes cells in vitro and as an injectable hydrogel for delivering chondrocytes cells in vivo. These results illustrated that HA-SH hydrogels with controllable gelation process, intelligent degradation behavior, excellent biocompatibility and convenient operational characteristics supplied potential clinical application capacity for tissue engineering and regenerative medicine.

A review of gradient stiffness hydrogels used in tissue engineering and regenerative medicine

“…Hydrogels of different storage modulus (up to 44.6 kPa) showed different gelation time and effect on chondrocytes properties. Cell initial density, culture time as well as hydrogel mechanical and biodegradation affect chondrocytes proliferation and morphology, which may due to the difference of degradation behavior of HA‐SH hydrogel and microenvironment surrounding the cells between in vivo and in vitro . Alginate hydrogels that form pores in situ are characterized and used as a physical scaffold for cell infiltration.…”

“…The delivery of chondrocytes was influenced by the storage modulus of hydrogels. In this research, the novel stiffness controllable self‐crosslinking smart hydrogels with in situ gelation properties showed convenient operational characteristics and supplied potential clinical application capacity for tissue engineering and regenerative medicine . Advances in biomaterial engineering allow the design of 3D hydrogel culture systems.…”

Photocrosslinked tyramine-substituted hyaluronate hydrogels with tunable mechanical properties improve immediate tissue-hydrogel interfacial strength in articular cartilage

“…To fully characterize the viscoelastic mechanical properties of TA-HA gels for use in soft tissue applications, the rheometric properties will need to be characterized. In a study by Bian et al[63], the storage modulus of self-crosslinking thiol substituted HA gels were measured. Gels with < 38% substitution had less than a 0.6 kPa change in the storage modulus between frequencies of 0.5 to 10 Hz.…”

An Extracellular Matrix‐Mimicking Hydrogel for Full Thickness Wound Healing in Diabetic Mice

“…Thiolated hyaluronic acid derivatives (HASH) were synthesized according to a previously reported method ( Scheme 1 ). Briefly, HA (1 g, 2.5 mmol disaccharide repeats) and NHS (575 mg, 5 mmol) were dissolved in 80 mL of deionized water for 30 min. Then EDCI (958 mg, 5 mmol) was added to the mixture, and kept stirring for 2 h. Specifically, CSA·HCl (855 mg, 7.5 mmol) was dissolved in 10 mL of dilute hydrochloric acid (HCL, pH 3.0), and then the CSA·HCl solution was added into HA solution.…”