The numerous preparation techniques adopted are physical cross-linking, chemical cross-linking grafting polymerisation, and radiation cross-linking [19]. Based on the kinds of cross-link junctions, hydrogels can be classified into two groups: the chemically cross-linked and the physically cross-linked. Chemically cross-linked gels have stable junctions, in which covalent bonds are present between different polymer chains, thus leading to outstanding mechanical strength. Such modifications can increase the mechanical properties and viscoelasticity for uses in biomedical and pharmaceutical arenas [20]. Cross-linking is a stabilization procedure in polymer chemistry that resulting in the multi-dimensional extension of polymeric chains, leads to network structures. By crosslinking, hydrogels are formed into stable structures that differ from their raw materials. Though chemical cross-linking is an extremely inventive technique for the formation of hydrogels, the cross-linkers used in hydrogel preparation should be extracted from the hydrogels before use, due to their reported toxicity, whereas, in physically cross-linked gels, dissolution is prohibited by physical interactions, such as ionic interactions, hydrogen bonds or hydrophobic interactions [21, 22].

Injectable gels have numerous advantages over preformed implants, including their non-invasive introduction in vivo and the capability to be used to homogeneously macromolecules and encapsulate cells. The elastic characteristics of gel can be improved by variable the amount of concentration. Mechanical, biochemical and rheological properties of hydrogels are powerfully connected to their chemical composition, the way hydrogel is polymerized and density of cross linkers [23].

Despite considerable improvement in therapeutic approaches, skin disorders remain a challenging discussion. Over the past decade, research on hydrogel-based material for prepose of skin regeneration has become a promising approach [24].The incorporation of nanoparticles into the hydrogel and transfer in the damaging side as a wound dressing has shown acceptable results including, improving absorption of wound exudates, decreasing infections and adverse allergic effects influences improving wound regeneration [25]. Natural hydrogel polymers exhibit biological activities such as cell recruiting, improving neo-vasculature, and modulation of the inflammatory microenvironment [26, 27]. Among the natural hydrogels-based materials for skin tissue engineering, alginate has been considered a biocompatible and hemostatic polymer [27]. Due tothe poor mechanical characteristics of alginate, we hypothesized that the incorporation of Zinc-dopped laponite nanoparticles in alginate could improve mechanical properties and facilitate the fabrication of regular microporous structures that are suitable for cell nutrient transferring. Moreover, Curcumin (CUR) is documented as a harmless composite by the Food and Drug Administration (FDA) and, numerous preclinical and clinical studies assessed in this field. The wound healing process is a dynamic and complex process. During the inflammatory phase of wound healing CUR could regulate inflammation via regulating main signaling pathways and reducing concentration target molecules like TNF-and IL-1 and fibroblast recruiting, releasing protease and removing the rate of reactive oxygen species (ROS) as well [28]. In the proliferation stage, CUR also has a critical role in the differentiation of fibroblast and collagen synthesis, decreasing the level of the number of membrane matrix metallo-proteinases (MMPs) [29]. We hypothesized that the incorporation of Zinc-dopped laponite containing curcumin within alginate (Al/La/Zn-CUR) could promote the viability of the cell-encapsulated alginate, which in turn could fabricate the novel structure for maximum transporting nutrients and exit waste products in the wound site.

Our results were in line with the published literature data, emphasizing that the incorporation of Zinc-dopped laponite containing CUR within alginate could be beneficial in improving viability.

As mentioned above, due to the aforementioned fantastic alginate assets, hydrogels as promising constituents are highly suitable for diverse applications, particularly for diagnostic and therapeutic manners in biomedical areas. They not only can assist as a carrier to load and transfer remedy or protein to tissues [5, 30] but also can act as scaffold to replace damaged tissues and organs, helping as wound dressings, barriers, or adhesives membrane between material and tissue surfaces [31, 32]. Recently, tissue engineering technology has assisted in fabricate various commercial wound dressings based on natural and synthetic hydrogels [33]. Wound dressings based on biological nanocomposites have helped to increase wound healing managements [34, 35]. In a study that was prepared from a wound dressing based on zinc oxide- alginate, antibacterial outcomes, they had somewhat advanced antibacterial activities against S. aureus than E. coli.

Consequently, sodium alginate (SA)-Zinc oxide (ZnO) nanoparticle has the potential to be used as a wound healing material in biomedical applications [36]. Laponite is a nanomaterial with a disc-like crystal structure that has a large surface area compared to its volume. Duo to it exhibit unique properties like low toxicity when interacting with the body’s microenvironment is widely considered in regenerative medicine [37, 38]. Moreover, in the tissue engineering field, Laponite could suppress the immunological body responses and stimulate differentiation and proliferation of host cells, when applied as a vector. Also, this nanoparticle, when incorporated in hydrogel /scaffolds structure could increase mechanical resistance as well [39, 40].