Definition/Introduction

Alginates are a family of compounds that naturally occur in the cell wall and extracellular matrix of various species of brown seaweed, often comprising up to 40% of the plant’s biomass. Some species of bacteria have also been found to produce alginates, including the commonly infectious Pseudomonas aeruginosa.[1] Alginates see extensive use in the cosmetics, food, and biomedical industries due to their physical properties and inherent biocompatibility. 

The building blocks of alginates are guluronic and mannuronic acid, both monosaccharides closely related to glucose. These building blocks form long chains that, with the addition of water, generate an anionic polysaccharide scaffold within an aqueous matrix. Varying the proportions of guluronic and mannuronic acid generates alginate compounds with differing physical and chemical properties.[2] With the addition of an ionic crosslinker such as calcium or barium, alginates form a resilient, flexible, solid/semisolid hydrogel. These hydrogels have been used extensively as a tissue interface in wound dressings and as a construct for encapsulating cells and other therapeutic compounds.

Issues of Concern

Fundamental Properties of Alginates

Biocompatibility

Various forms of alginate are approved by the FDA for use primarily as a thickening agent, and alginate is widely known to be biocompatible and biodegradable.[3] While some evidence indicates that alginate hydrogels are non-antigenic, in vivo research has shown that animals and humans alike often mount a generalized foreign body immune response when significant amounts of alginate are introduced into the physiologic environment. With that said, various materials have been studied as modifying and augmenting agents to reduce the immunogenicity of alginate, with varying promise[4].

Permeability

Alginates are hydrophilic by nature, and crosslinked hydrogels contain a significant aqueous component. Due to the structural chemistry of alginate scaffolds, water and other small molecules diffuse freely throughout the hydrogel. Because of this, many therapeutic compounds diffuse out of alginate hydrogels at predictable and consistent rates, making them useful biomaterial carriers in drug delivery.[5] Additionally, this characteristic allows alginate hydrogels to equilibrate with their environment to some extent, and consequently, alginate hydrogels can maintain a relatively physiologic internal environment in vivo conditions.[6]

Variability

Alginates crosslink to form hydrogels under a generally flexible set of conditions, which allows for significant variability in the composition and characteristics of the resultant biomaterial. A wide variety of compounds can be combined with alginates without disrupting their ability to crosslink, including therapeutic molecules, extracellular matrix components, and other biomaterials like chitosan. Various crosslinking agents and methods can be employed to generate hydrogels with a range of stiffness and degradative characteristics. This compositional flexibility allows alginate to act as a versatile, modifiable, biologically compatible biomaterial construct.[7]

Clinical Significance

Alginates in Wound Dressings

Alginate hydrogels have extensive utilization as wound interfaces in dressings intended to support healing following burns, pressure ulcers, venous ulcers, and other exudative cutaneous wounds. While the indications of alginate wound dressings are different in each of these contexts, a few underlying principles are generally relevant. Because alginates allow for the relatively free diffusion of water and solutes, alginate dressings are thought to generate a relatively physiologic environment at the wound interface that encourages healing. Additionally, some research postulates that calcium release from alginate hydrogels crosslinked with calcium stimulates coagulative pathways and which results in a healing response. While alginate dressings see extensive use in wound healing, few well-controlled studies definitively link their usage to improvements in outcomes.[8] It remains undetermined whether this is due to a lack of published evidence or a lack of benefit achieved with these dressings.

Alginates in Encapsulation

Modern drug delivery systems often utilize a “carrier” construct that protects and facilitates the delivery of the intended therapeutic compound(s). Because of their flexibility, modifiability, and well-studied biocompatibility, alginate-based hydrogels are often candidates for this application.[9] Therapeutic agents ranging from insulin to doxorubicin to entire cells and tissues have been encapsulated within alginate, delivered into the physiologic environment, and studied in preclinical and clinical trials. Because alginates can crosslink with agents that are generally compatible with physiologic function (like calcium chloride solutions), cells and tissues can be added to alginates before crosslinking, making alginate hydrogels particularly advantageous biomaterial constructs for living cell and organoid encapsulation.[10]

For patients with extensive cutaneous wounds, healthcare staff should consider alginate dressings as a means of maintaining a moist and semi-physiologic wound environment. However, it bears mentioning that a systematic review has failed to substantiate the superiority of alginate dressings over other dressing types.