**2. Advances in tailored hybrid alginate compositions in biotechnology applications**

The alginate and its derived composites have widespread uses from chromatography [23] and wound healing [24] to tissue engineering, drug delivery [25], enzyme immobilisation, and cell encapsulation (**Figure 3**) [26].

Alginate exhibits instantaneous gelation in the presence of multivalent cations such as divalent cations (Ca2+, Ba2+) [17, 27] and cationic polymers such as poly-L-lysine and chitosan [28, 29]. Due to its excellent gelation feature and biocompatibility, alginate has encapsulated a variety of entities as macroscopic alginate-based spheres such as beads and microcapsules [30]. There are two major classical strategies for encapsulating biomolecules in macroscopic alginate spheres. First is the general approach of dripping an alginate solution containing the biomolecules or cells of interest into a crosslinker solution, producing alginate beads instantaneously. In contrast, an inverse approach in which the viscous solution containing a crosslinker and biomolecules are added in drops into an alginate solution, yielding microcapsules having a viscous core and an alginate shell as shown in **Figure 4** [31]. These approaches are seamless and beneficial for active biomolecule immobilisation, but the associated undesirable leakage of the enclosed entity from the matrix limits their more comprehensive application [32]. Many attempts have continuously been made to address the leakage limitation associated with encapsulation approach. Such attempts


**Figure 3.** *Biotechnology applications of hybrid-alginate based systems.*

**Figure 4.**

*Two classical approaches of encapsulating biomolecules within macro/microscopic alginate spheres.*

include the use of nanoparticles to immobilise the enzyme followed by entrapment within the hydrogel [33], covalent immobilisation [34], covalent affinity immobilisation [35, 36], modulation of the pore of the alginate matrix with other materials such as polycations synthetic polymers [37], natural polymers [38], crosslinking agents [39], inorganics [40] among others.
