Marine Algae-Derived Bioactive Compounds and Biomaterials: Pharmaceutical Applications and Therapeutic Advances in Medical and Dental Sciences

INTRODUCTION

Algae, derived from the Latin term historically associated with Hepaticae and introduced by Linnaeus in 1753, represent a diverse group of chlorophyll-containing organisms ranging from microscopic unicellular forms to giant seaweeds exceeding 70 M in length (El Gamal, 2010). They are broadly classified into macroalgae and microalgae, with macroalgae comprising green (Chlorophyceae), brown (Phaeophyceae), and red algae (Rhodophyceae). Marine algae grow rapidly without requiring freshwater, arable land, or fertilizers, making them an environmentally sustainable resource (Veluchamy et al., 2020). Rich in bioactive compounds such as carotenoids, omega-3 fatty acids, essential amino acids, vitamins, minerals, flavonoids, polysaccharides, tannins, and bromophenols, marine algae possess significant nutritional and therapeutic value (Achankunju et al., 2023; Kaliaperumal et al., 2015; Rashad et al., 2020). They are widely used in food, animal feed, fertilizers, traditional medicine, pharmaceuticals, cosmetics, textiles, and biofuel production (Duc et al., 2021; Kavitha et al., 2019). Algae also play a crucial ecological role by contributing to oxygen production and serving as the primary food source in marine ecosystems (Xie et al., 2022).

METHODOLOGY

A literature search was conducted from 2000 to 2025 using PubMed, Scopus, and Google Scholar to identify relevant studies on marine algae-derived bioactive compounds and their medical and dental applications. Retrieved articles were screened for relevance, relevant data were extracted, and the findings were narratively synthesized to provide a comprehensive overview of current evidence and emerging therapeutic applications.

Biocompatibility of marine algae

Marine algae exhibit strong biocompatibility, making them promising for biomedical applications. Brown algae-derived 3D scaffolds supported HFF cell proliferation with no adverse effects in rats, and purification of sodium alginate improved safety without altering its properties (Paudel et al., 2014). Red algae j-carrageenan hydrogels showed no cytotoxicity, low oxidative stress, and minimal inflammation in vivo (Popa et al., 2014). Green algae cellulose scaffolds from Cladophora and Ulva enhanced fibroblast viability and supported long-term growth (Bar-Shai et al., 2021). Microalgae like Spirulina, Chlorella, and diatoms were largely non-toxic in vitro and in vivo, with Spirulina-based treatments showing selective cancer cell toxicity and safe clearance in mice (Zhong et al., 2021).

Pharmacological activity and applications of marine algae in medical science

Marine algae are increasingly recognized for their wide-ranging medical applications due to their rich content of bioactive compounds (Table 1). For skin health, substances like fucoidans, fucoxanthin, and phlorotannins offer antioxidant, anti-inflammatory, and photoprotective benefits, while compounds such as ascophyllan support skin whitening and anti-cancer effects. Compounds like dieckol, fucoxanthin, and fucosterol reduce lipid peroxidation, DNA damage, and boost antioxidant enzymes. Red algae peptides, including those from Pyropia yezoensis, show strong ACE inhibition. Phlorotannins from Sargassum fusiforme and Ecklonia cava, like dieckol and phlorofucofuroeckol A, lower blood pressure and boost nitric oxide (Fernando et al., 2022).

Algae also show strong antidiabetic, antioxidant, and neuroprotective activities-helping regulate blood glucose, protect against oxidative stress, and improve cognitive function. Extracts from Ascophyllum nodosum, alginates, and agar aid in regulating glucose and starch digestion. Phlorofucofuroeckol-A and Ecklonia polyphenols help prevent diabetes complications by inhibiting AGE, ACE, and oxidative stress (Jimenez-Lopez et al., 2021).

Their anticancer properties are driven by compounds like fucoidan and phlorofucofuroeckol A, which inhibit cancer cell growth and enhance chemotherapy outcomes (Biris-Dorhoi et al., 2022). Compounds like fucofuroeckol-A enhance fungal susceptibility to treatments like fluconazole. Marine algae possess broad-spectrum antiviral properties by inhibiting viral entry, replication, and spread. Phlorotannins from Ecklonia cava inhibit HIV replication, while compounds like Griffithsin and ulvan target HSV and encephalitis viruses. Additionally, marine algae demonstrate antibacterial, and antiparasitic effects through mechanisms like disrupting cell membranes, inhibiting pathogen replication, and enhancing immune defense (Besednova et al., 2021). Beyond infection and chronic disease management, marine algae support cardiovascular health with antihypertensive, anticoagulant, and antihyperlipidemic properties, attributed to compounds like phlorotannins and sulfated polysaccharides (Seca et al., 2018).

Their anti-inflammatory, hepatoprotective, and anti-allergic effects further expand their therapeutic value. Wound healing is a complex process that benefits from suitable dressings like hydrogels, which provide mechanical support and maintain moisture. Alginate-based dressings, available as films, hydrogels, foams, and more, form gels upon contact with fluid and are highly absorbent but unsuitable for dry wounds. Compared to traditional dressings, alginate hydrogels are non-toxic, absorb water well, don’t stick to wound tissue, and enable lateral wicking by drawing exudate away from the wound to healthy skin, minimizing damage during removal (Thomas et al., 2011).

In biomedical engineering, marine-derived polysaccharides are used in drug delivery systems, wound healing, and tissue engineering due to their biocompatibility, biodegradability, and ability to mimic natural tissues. Carrageenan and fucoidan-based microspheres and nanoparticles provide tailored release and therapeutic effects like anticoagulation. Alginate encapsulation protects drugs, allowing delayed release and improved stability and efficacy. Marine biomaterials like κ-carrageenan hydrogels support cell growth, chondrogenesis, and matrix formation in tissue engineering. Alginate hydrogels provide biocompatible scaffolds resembling the extracellular matrix, ideal for bone regeneration. From enhancing immune function to supporting bone and liver health, algae-derived substances like fucoidan, carrageenan, alginate, and ulvan represent versatile and natural alternatives for a wide range of medical applications (Zhang et al., 2021).

Applications of marine algae in dental sciences

Marine algae have shown significant potential in dentistry due to their antimicrobial, anti-inflammatory, and anticariogenic properties (Table 2). Marine algae show strong antimicrobial activity against oral pathogens causing dental caries, including Streptococcus mutans and Candida albicans. Cariogenic bacteria like Streptococcus mutans and Lactobacillus metabolize sugars into acids, causing dental caries. Endotoxins, also known as Lipopolysaccharides (LPS), can trigger severe immune responses, leading to conditions like sepsis and septic shock. It has been found that marine algae extract, fucoidan, possesses such properties (Oka et al., 2020).

Ascophyllum nodosum (kelp) reduces dental plaque and calculus by breaking bonds on the tooth surfaces. Its antiplaque effects are attributed to esterified mannitol, laminaran, and sulfated uronic acids. This kelp can be used in powders, suspensions, or tablets. These properties make it a promising natural agent for dental hygiene products. Pleurochrysis carterae and Emiliania huxleyi also possess calcifying properties beneficial for tooth mineralization. Algae-derived compounds such as fucoidan, eckols, and chitooligosaccharides also support pulp regeneration, manage periodontitis, treat aphthous ulcers, and alleviate temporomandibular joint pain (Huang et al., 2021; Mikulewicz et al., 2015).

Moreover, algae-based materials like alginate play vital roles in advanced dental applications, including drug delivery, bioactive coatings, and tissue engineering. These biomaterials support endodontic healing, periodontal regeneration, and bone formation, while also offering innovative solutions for conditions like oral mucositis, oral submucous fibrosis, and salivary gland damage. Fucoidan reduces setting times, making it a promising additive for pulp-capping materials. Fucoidan, known for its anti-inflammatory and antioxidant properties, was shown to improve saliva flow, reduce fibrosis, increase mucin-rich tissue, and preserve salivary and myoepithelial cells, helping to alleviate salivary gland dysfunction after radioiodine therapy. Fucoidan from marine algae supports bone regeneration in periodontal therapy by enhancing osteocalcin release when combined with tricalcium phosphate-chitosan scaffolds. It stimulates osteogenic differentiation in human mesenchymal stromal cells. Fucoidan combined with polydopamine boosts alkaline phosphatase activity and upregulates key osteogenic markers in periodontal ligament stem cells.

Fucoidan combined with deoxycholic acid forms nano-micelles that enhance drug retention, accelerate healing, reduce inflammatory cell infiltration, and inhibit NF-κB activity, showing superior anti-inflammatory effects compared to standard cannabidiol treatments. Fucoidan shows therapeutic promise by targeting the MEG3 gene and myofibroblast markers, regulating miR-181a and Egr1 to inhibit fibrosis and improve OSF outcomes. Fucoidan injections reduce tooth movement during orthodontic retention by improving bone mineral density. It increases anti-inflammatory macrophages (F4/80+CD206+) and markers like IL-10 and arginase 1, while lowering pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) which enhances tooth stability via the STAT3 pathway. Their role in modulating inflammation, promoting cell proliferation, and inhibiting osteoclastic activity makes marine algae promising natural agents in both restorative and preventive dental care (Hudiyati et al., 2024).

Current marine algae-based dental products

Anil et al. explain that agar, from red algae, and alginate, from brown seaweeds are marine hydrocolloids used in dental impressions. Alginate impression material, which is inexpensive and easy to handle, and frequently used to make impressions in general clinical settings is extracted by crushing brown algae in hot alkaline solution to form sodium alginate, which is then filtered, acidified to alginic acid, and dehydrated with alcohol. Adding sodium carbonate converts it back to sodium alginate, dried and milled (Anil et al., 2017).

Alginate and carrageenan, extracted from brown and red seaweeds, respectively, are key ingredients in toothpaste for their gel-forming, stabilizing, and thickening properties. Carrageenan, especially iota type, is commonly added at ~1% for tooth decay treatment. Algal extracts like Laminaria japonica and Aphanizomenon flosaquae offer antimicrobial benefits and are used in dental gels. Fucoidan from marine algae is also incorporated into toothpaste formulations (Anil et al., 2017).

Seaweed-based chewing gums enriched with minerals help protect teeth from acid damage and promote remineralization. Algal extracts, such as from Enteromorpha linza and green algae species, show antimicrobial and antifungal effects against oral bacteria linked to tooth decay and gum disease. A study with 55 participants found E. linza mouthwash reduced gum bleeding, swelling, and plaque, matching commercial products. Methanol extracts of Ulva fasciata and others showed strong antibacterial activity (Mikulewicz et al., 2015).

Biopolymeric films, including polylactic acid, are used in dentistry for regeneration, drug delivery, and preventing caries and biofilms. They aid restorative, prosthetic, periodontal, and implant therapies, reducing corrosion and friction. Nanocapsules with bioadhesive properties are being developed (Sudhakar et al., 2024).

Bio-inks made from natural biopolymers like carrageenan and alginate offer biocompatibility and versatility for 3D printing in dentistry. They have excellent rheological properties and blend well with other materials. They are used for 3D models, guides, scaffolds, membranes, dentures, and prostheses in various dental fields, including oral surgery and prosthodontics (Sudhakar et al., 2024).

AlgiPore/C GRAFT/AlgOss (ACA) is a hydroxyapatite bioceramic from marine algae with a microporous structure that supports bone growth and implant osseointegration. Symbios® Biphasic BGM modifies ACA with ß-tricalcium phosphate for faster resorption and bone regeneration, though clinical data is limited. Biopolymer-based membranes are preferred for their biocompatibility and tissue-mimicking properties (Sudhakar et al., 2024).

CONCLUSION

Marine algae play a significant role in various fields due to their biocompatibility, biodegradability, anti-inflammatory, and antimicrobial effects. These natural resources are utilized in applications ranging from pharmaceuticals to food supplements, and notably in dentistry for periodontal therapy, bone regeneration, dental implant coatings, prevention of dental caries, etc, with compounds like alginate and fucoidan. Additionally, marine algae extracts have shown promise in treating conditions such as mucositis, and oral submucous fibrosis, and enhancing salivary flow in patients undergoing radioiodine therapy, offering innovative solutions for improving oral health and clinical outcome.