pH and redox sensitive albumin hydrogel: A self-derived biomaterial

The recent developments in biomaterial research have resulted in various innovative materials with clinical applications. However, intensive research is required for developing materials for therapeutic applications1. In the field of biomaterials research, hydrogels are known to deliver proteins, drugs, antibodies, DNA, growth factors and immunological molecules2,3. The preparation of hydrogels for biomedical applications depends on the functional properties, such as swelling, biocompatibility, biodegradability, non-toxicity and mechanical stability, of the materials. The various polymeric materials and cross-linking systems in hydrogels help in enhancing its delivery efficiency. Recently, stimuli-responsive hydrogels were reported to be an efficient delivery system of therapeutic molecules to the targeted site. This stimuli-responsive property can be integrated into hydrogels using appropriate functionalisation chemistry on the polymeric material4,5,6,7,8. Although the pH responsive property of hydrogels has been widely exploited, its redox response property has not been much reported9,10,11. This redox property can be achieved through functionalisation with thiol moieties to the polymer backbone of either natural or synthetic origin12,13,14,15,16,17. Natural materials are biocompatible and biodegradable compared to synthetic polymeric materials. Proteins, a natural material, can be effectively used due to their availability and unique structural properties. Various proteins, such as collagen, gelatin and albumin, are used in tissue engineering and drug delivery. Currently, autogenic sources are being explored for protein harvesting. Of these proteins, albumin can be used in various applications as they can be easily harvested from human blood plasma. Serum albumin, the most abundant globular protein in blood, consists of 580 amino acid residues (66 kDa) with 17 disulphide bridges and has 1 free sulphydryl group in a single polypeptide chain. The protein consists of 54% alpha helix and 40% beta structure18, and is about 50 g/L or two-third of plasma protein. It functions as a transport protein for numerous endogenous and exogenous substances. Studies have reported that albumin can be transformed into a hydrogel or any other biomaterials. Serum albumin has been widely used as a backbone material in the preparation of hydrogels, microspheres, nanoparticles and scaffolds using suitable cross-linkers such as glutaraldehyde19,20,21. However, although the addition of glutaraldehyde to hydrogel helps in crosslinking and imparting stability, its toxicity is of concern19. This problem can be overcome if the innate di-sulphide bridges of proteins are exploited in a suitable way through redox chemistry. Thus, the use of external cross-linkers can be avoided and a redox responsive property can be achieved22,23,24,25,26. Hence, there is a requirement for an autogenic material (i.e., a unique material derived from an individual’s blood protein–human serum albumins, HSA) in the preparation of stimuli-responsive hydrogels. Bovine serum albumin (BSA) could serve as a valuable alternate model to HSA due to its medical importance, low cost, high availability and about 76% similarity in molecular structure with HSA. Hence, in this study, we attempted to prepare pH and redox responsive self-derived BSA hydrogel using glutathione as a reducing agent. The hydrogel was further characterized for its physical and mechanical stability, biodegradability and in vitro and in vivo biocompatibility.