Alginate: Properties and biomedical applications

Polysaccharides, the most abundant biopolymers in nature, have attracted the attention of researchers and clinicians due to its practicality in biomedical and pharmaceutical sciences. These biomaterials have high bioavailability and play structural and functional roles in living organisms. Polysaccharides are classified into several groups based on their origin, including plant polysaccharides and marine polysaccharides (like chitosan, hyaluronic acid, dextran, alginates, etc.) with specific applications. These biopolymers possess unique physicochemical (such as surface functional groups, solubility, and stability), mechanical (like mechanical strength and tensile), and biomedical (such as antioxidant activity, biocompatibility, biodegradability, renewability, and non-immunogenicity) characteristics which have made them excellent platforms for a wide variety of biomedical and pharmaceutical applications. Ease of extraction and different preparation approaches are mentioned as other potential properties of polysaccharides that further improved their practicality in biomedical sciences. They have high drug/bioactive encapsulation capacity and sustained/controlled release manner in in vivo microenvironments. The anti-inflammatory and immunomodulation, stimuli-responsive drug/bioactive release, and passive and active drug/bioactive delivery are considered the potential features of these biopolymers in pharmaceutical sciences. Polysaccharides have indicated practical applications in biomedical sciences, including biosensors, tissue engineering, implantation, wound healing, vascular grafting, and vaccines. This review highlights the advances of polysaccharide-based materials in biomedical and pharmaceutical sciences.

Polyurethanes (PUs) have properties that make them promising in biomedical applications. PU is recognized as one of the main families of blood and biocompatible materials. PU plays a vital role in the design of medical devices in various medical fields. The structure of PU contains two segments: soft and hard. Its elastomeric feature is due to its soft segment, and its excellent and high mechanical property is because of its hard segment. It is possible to achieve specific desirable and targeted properties by changing the soft and hard chemical structures and the ratio between them. The many properties of PU each draw the attention of different medical fields. This work reviews PU highlighted properties, such as biodegradability, biostability, shape memory, and improved antibacterial activity. Also, because PU has a variety of applications, this review restricts its focus to PU’s prominent applications in tissue engineering, cardiovascular medicine, drug delivery, and wound healing. In addition, it contains a brief review of PU’s applications in biosensors and oral administration.

Alginates are one of the natural polysaccharides that are found in numerous applications in biomedical science and engineering. Alginates are attractive for wound healing, tissue engineering, and drug delivery applications. This is due to the favorable properties of alginates, including biocompatibility, low toxicity, abundant availability, and ease of gelation. Chemical functionalization like oxidation is one potential way to generate alginate derivatives with low molecular weight. This research studied the ratio of oxidation agent and sodium alginate as substrate. The oxidation reaction led to pyran ring opening and the formation of di-aldehyde, the so-called alginate dialdehyde (ADA) as much as 0.82 and 0.12 mol of aldehyde per mol repeating unit of alginate. The advantages of ADA are lower molecular weight and newly formed active aldehyde functional groups, which depend on the degree of oxidation. The new available functional groups open a new opportunity to conduct reductive amination reactions to graft a new targeting branch on the alginate structure. This reaction could be conducted using sodium cyanoborohydride, sodium borohydride, and picoline borane complex. The newly formed polymer product can be formed as hydrogel either using Schiff base reaction with gelatin to form crosslinking or with ionic crosslinker like calcium chloride. The resulting hydrogel is shear-thinning and self-healing, making it suitable for biomedical applications. The grafting study of ADA with plant lectin Wheat Germ Agglutinin (WGA), generated a microgel product suitable for curcumin encapsulation. The cytotoxicity study demonstrated that the microgels at low concentrations were suitable for the drug delivery matrix.

Adding carbonyl groups into the hydrogel matrix improves the stability and biocompatibility of the hydrogels, making them suitable for different biomedical applications. In this review article, we will discuss the use of hydrogels based on polysaccharides modified by oxidation, with particular attention paid to the introduction of carbonyl groups. These hydrogels have been developed for several applications in tissue engineering, drug delivery, and wound healing. The review article discusses the mechanism by which oxidized polysaccharides can introduce carbonyl groups, leading to the development of hydrogels through cross-linking with proteins. These hydrogels have tunable mechanical properties and improved biocompatibility. Hydrogels have dynamic properties that make them promising biomaterials for various biomedical applications. This paper comprehensively analyzes hydrogels based on cross-linked proteins with carbonyl groups derived from oxidized polysaccharides, including microparticles, nanoparticles, and films. The applications of these hydrogels in tissue engineering, drug delivery, and wound healing are also discussed.

Chapter 10 - Alginate microspheres: Synthesis and their biomedical applications

Polymeric hydrogels have drawn considerable attention as a biomedical material for their unique mechanical and chemical properties, which are very similar to natural tissues. Among the conventional hydrogel materials, self-healing hydrogels (SHH) are showing their promise in biomedical applications in tissue engineering, wound healing, and drug delivery. Additionally, their responses can be controlled via external stimuli (e.g., pH, temperature, pressure, or radiation). Identifying a suitable combination of viscous and elastic materials, lipophilicity and biocompatibility are crucial challenges in the development of SHH. Furthermore, the trade-off relation between the healing performance and the mechanical toughness also limits their real-time applications. Additionally, short-term and long-term effects of many SHH in the in vivo model are yet to be reported. This review will discuss the mechanism of various SHH, their recent advancements, and their challenges in tissue engineering, wound healing, and drug delivery.

Porous-based biomaterials for tissue engineering and drug delivery applications

Keratinous materials: Structures and functions in biomedical applications.

Chitosan (CS), a versatile biopolymer obtained through the deacetylation of chitin, has gained significant interest in biomedical and pharmaceutical applications due to its biocompatibility, biodegradability, and unique gel-forming capabilities. This review comprehensively analyzes CS-based gel development, covering its extraction from various natural sources, gelation mechanisms, and biomedical applications. Different extraction methods, including chemical, biological, and green techniques, are discussed regarding efficiency and sustainability. The review explores the physicochemical properties of CS that influence its gelation behavior, highlighting various gelation mechanisms such as physical, ionic, and chemical cross-linking. Recent advances in gel formation, including Schiff base reactions, Diels-Alder click chemistry, and thermosensitive gelation, have expanded the applicability of CS hydrogels. Furthermore, CS-based gels have demonstrated potential in wound healing, tissue engineering, drug delivery, and antimicrobial applications, offering controlled drug release, enhanced biocompatibility, and tunable mechanical properties. The incorporation of nanomaterials, bioactive molecules, and functional cross-linkers has further improved hydrogel performance. The current review underscores the growing significance of CS-based gels as innovative biomaterials in regenerative medicine and pharmaceutical sciences.

Recently, many studies have focused on carrageenan-based hydrogels for biomedical applications thanks to their intrinsic properties, including biodegradability, biocompatibility, resembling native glycosaminoglycans, antioxidants, antitumor, immunomodulatory, and anticoagulant properties. They can easily change to three-dimensional hydrogels using a simple ionic crosslinking process. However, there are some limitations, including the uncontrollable exchange of ions and the formation of a brittle hydrogel, which can be overcome via simple chemical modifications of polymer networks to form chemically crosslinked hydrogels with significant mechanical properties and a controlled degradation rate. Additionally, the incorporation of various types of nanoparticles and polymer networks into carrageenan hydrogels has resulted in the formation of hybrid platforms with significant mechanical, chemical and biological properties, making them suitable biomaterials for drug delivery (DD), tissue engineering (TE), and wound healing applications. Herein, we aim to overview the recent advances in various chemical modification approaches and hybrid carrageenan-based platforms for tissue engineering and drug delivery applications.

Chondroitin sulfate (CS), a naturally occurring glycosaminoglycan, is renowned for its biocompatibility, biodegradability, and considerable role in wound healing and drug delivery applications. In wound healing, CS fosters tissue regeneration by augmenting cell signaling, extracellular matrix remodeling, and accelerating tissue repair. As a drug delivery system, CS acts as an adaptable carrier, improving stability, bioavailability, and controlled release of therapeutic agents. Its ability to form hydrogels and nanoparticles enables prolonged, site-specific drug delivery, ensuring targeted therapeutic action at injury sites. Recent advancements have focused on CS-based formulations for chronic wound treatment, emphasizing its role in tissue regeneration and faster healing. The integration of CS with biomaterials like collagen and hydroxyapatite further optimizes therapeutic outcomes. In addition to CS, chondroitinase ABC (chABC) has gained attention for its potential in wound healing and drug delivery. chABC, an enzyme that degrades chondroitin sulfate chains, promotes tissue repair by breaking down inhibitory extracellular matrix components and promoting cell migration. The combination of CS and chABC could offer synergistic effects, enhancing wound healing and drug delivery efficiency. Challenges remain in optimizing formulations for clinical use, including stability, scalability, and regulatory issues, but the future potential for CS and chABC in therapy is significant.

The significance of electrospinning as a method to create fibrous scaffolds for biomedical engineering and drug delivery applications

Alginates are polysaccharides resourced from natural sources such as brown algae and bacteria. Alginate is a natural, biodegradable, biocompatible and non-toxic polymer possessing numerous specific physicochemical properties. These properties are responsible for its wide applications in the emerging area of biomedical sciences. Alginates undergo crosslinking with di- or tri-valent metal ions at room temperature to form uniform, transparent, thermo-irreversible gels which are insoluble in water. These properties also help in the preparation of various formulations of Alginate. Formulation of Alginate hydrogel, can be accomplished by employing physical or chemical cross-linking strategies. Alginate hydrogels owing to their inherent properties encompass tremendous potential and will have wide applications in Drug Delivery as well as Biomedical sciences. Therefore, in view of the vast literature support, we have discussed the applications of alginate hydrogels in drug delivery as well as biomedical sciences. Various properties of alginates, their hydrogels along with the various techniques employed for fabricating alginate hydrogels have been reviewed.Keywords AlginateHydrogelChemical and physical cross-linkingDrug delivery

Large-area alginate/PEO-PPO-PEO hydrogels with thermoreversible rheology at physiological temperatures

Collagen, a fundamental structural protein in the extracellular matrix (ECM), plays a critical role in tissue engineering, regenerative medicine, and biomaterial development. It is involved in various biological functions, including wound healing, musculoskeletal health, cardiovascular integrity, and cancer progression. Due to concerns related to disease transmission, ethical considerations, and religious constraints associated with mammalian collagen sources, marine-derived collagen (MDC), particularly from fish skin and scales, has emerged as a promising and sustainable alternative. MDC exhibits superior biocompatibility, biodegradability, and low immunogenicity, making it suitable for applications in wound healing, drug delivery, and tissue engineering. Various extraction techniques, including acid solubilization, enzymatic hydrolysis, and deep eutectic solvent extraction, ensure high purity and preserved bioactivity, while characterization methods such as FTIR, SEM, and XRD confirm its structural integrity. Additionally, MDC-based composite scaffolds and hydrogels enhance fibroblast proliferation, angiogenesis, and osteoblast differentiation, supporting regenerative medicine applications. In oncology, collagen remodeling has been linked to cancer metastasis, with metastatic cells exhibiting enhanced reorganization of type I collagen fibers, promoting invasiveness. Despite these advantages, challenges such as collagen quality inconsistencies, mechanical strength limitations, and the need for extensive in vivo studies remain. Future research should focus on optimizing extraction techniques, improving mechanical stability through cross-linking strategies, and integrating emerging technologies such as 3D collagen-based scaffolds, CRISPR-mediated genetic modifications, and AI-driven molecular modeling. With continued advancements, MDC holds significant potential as a sustainable and effective biomaterial for biomedical, clinical, and industrial applications. Keywords: Collagen, Marine-Derived Collagen (MDC), Tissue Engineering, Regenerative Medicine, Wound Healing, Biomaterials, Drug Delivery, Cancer Metastasis, Extracellular Matrix (ECM), 3D Scaffolds, CRISPR, AI-Driven Molecular Modeling, Biocompatibility, Biodegradability, Sustainable Biomaterials