Alginate-Based Biomaterials in Tissue Engineering and Regenerative Medicine

Abstract

Today, with the salient advancements of modern and smart technologies related to tissue engineering and regenerative medicine (TE-RM), the use of sustainable and biodegradable materials with biocompatibility and cost-effective advantages have been investigated more than before. Alginate as a naturally occurring anionic polymer can be obtained from brown seaweed to develop a wide variety of composites for TE, drug delivery, wound healing, and cancer therapy. This sustainable and renewable biomaterial displays several fascinating properties such as high biocompatibility, low toxicity, cost-effectiveness, and mild gelation by inserting divalent cations (e.g., Ca²⁺). In this context, challenges still exist in relation to the low solubility and high viscosity of high-molecular weight alginate, high density of intra- and inter-molecular hydrogen bonding, polyelectrolyte nature of the aqueous solution, and a lack of suitable organic solvents. Herein, TE-RM applications of alginate-based materials are deliberated, focusing on current trends, important challenges, and future prospects.

Keywords: alginate; biomaterials; biomedical engineering; hydrogels; regenerative medicine; scaffolds; tissue engineering.

Figure 1

(A) The conformation of monomers and block distribution of alginate. Adapted from Ref [18] with permission, Copyright 2020 Springer Nature, licensed under the terms of the Creative Commons Attribution License (CC BY). (B) The physical/chemical modification processes, 3D bioprinting techniques, and TE-RM applications of alginate hydrogels. Adapted from Ref. [19] with permission. Copyright 2023 Elsevier.

Figure 2

Typical crosslinking approaches to form alginate hydrogels. Adapted from Ref. [23] with permission. Copyright 2020 Elsevier.

Figure 3

(A–F) Typical fabrication methods used in synthesizing alginate-based nanomaterials. Adapted from Ref. [17] with permission. Copyright 2020 Elsevier.

Figure 4

(A) Scanning electron microscopy (SEM) image of electrospun nanofiber mesh, showing the smooth and bead-free nano-scaled fibers. (B) Hollow tubular implant without perforations constructed from nanofiber meshes. (C) Tubular implant with perforations. (D) The composite was constructed from an electrospun nanofiber mesh tube applied for repairing the bone defect. (E) Picture of the defect after placement of a perforated mesh tube; the alginate inside the tube can be seen through the perforations. (F) A specimen was taken down after one week and the mesh tube was cut open. The alginate was still present inside the defect, with a hematoma present at the bone ends. (G) The release kinetics of alginate >21 days (in vitro); sustained release of the rhBMP-2 could be detected during the first week. Adapted from Ref. [74] with permission. Copyright 2010 Elsevier.

Figure 5

(A) The representative corneal stroma structure (layers of the cornea and cellular structure of stroma). (B) The preparative process of (i) micro-patterned silk nanofibril (SNF) incorporated gelatin methacrylate (S/G) composite films through a micro-molding technique, under ultraviolet light, and (ii) double-layer micro-patterned S/G-sodium alginate (SA) film, after crosslinking of SA using CaCl₂ solution. GelMA: gelatin methacrylate. Adapted from Ref. [89] with permission. Copyright 2021 Elsevier.

Figure 6

(A) The preparative process of bioinspired alginate/gum Arabic hydrogels with sustained drug delivery behavior for chronic wound healing. (B) Atomic force microscopy (AFM) topographic micrograph of the sundew mucilage. (C) The hydrogels were generated by Ca²⁺-dependent crosslinking between sodium alginate and gum Arabic. Adapted from Ref. [96] with permission. Copyright 2017 American Chemical Society.