ABSTRACT
In this study, the disulfide-linked hyaluronic acid (HA) hydrogels were optimised for potential application as a scaffold in tissue engineering through the Quality by Design (QbD) approach. For this purpose, HA was first modified by incorporating the cysteine moiety into the HA backbone, which promoted the formation of disulfide cross-linked HA hydrogel at physiological pH. Utilising a Design of Experiments (DoE) methodology, the critical factors to achieve stable biomaterials, i.e. the degree of HA substitution, HA molecular weight, and coupling agent ratio, were explored. To establish a design space, the DoE was performed with 65 kDa, 138 kDa and 200 kDa HA and variable concentrations of coupling agent to optimise conditions to obtain HA hydrogel with improved rheological properties. Thus, HA hydrogel with a 12 % degree of modification, storage modulus of ≈2321 Pa and loss modulus of ≈15 Pa, was achieved with the optimum ratio of coupling agent. Furthermore, biocompatibility assessments in C28/I2 chondrocyte cells demonstrated the non-toxic nature of the hydrogel, underscoring its potential for tissue regeneration. Our findings highlight the efficacy of the QbD approach in designing HA hydrogels with tailored properties for biomedical applications.
Subject(s)
Biocompatible Materials , Chondrocytes , Disulfides , Hyaluronic Acid , Hydrogels , Rheology , Tissue Engineering , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Hydrogels/chemical synthesis , Disulfides/chemistry , Chondrocytes/drug effects , Chondrocytes/cytology , Biocompatible Materials/chemistry , Biocompatible Materials/chemical synthesis , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Animals , Cell Line , Cell Survival/drug effects , Humans , Hydrogen-Ion ConcentrationABSTRACT
Tissue regeneration is a prominent area of research, developing biomaterials aimed to be tunable, mechanistic scaffolds that mimic the physiological environment of the tissue. These biomaterials are projected to effectively possess similar chemical and biological properties, while at the same time are required to be safely and quickly degradable in the body once the desired restoration is achieved. Supramolecular systems composed of reversible, non-covalently connected, self-assembly units that respond to biological stimuli and signal cells have efficiently been developed as preferred biomaterials. Their biocompatibility and the ability to engineer the functionality have led to promising results in regenerative therapy. This review was intended to illuminate those who wish to envisage the niche translational research in regenerative therapy by summarizing the various explored types, chemistry, mechanisms, stimuli receptivity, and other advancements of supramolecular systems.
