Alginate-based biomaterials in orthopedics: What are the prospects for bacterial alginate?

Abstract

The mini-review explores the potential use of alginates produced biotechnologically by bacteria for the development of various implantable biomaterials intended for bone and cartilage tissue regeneration in orthopedics: the recent studies on the use of algal alginate-based biomaterials in the form of hydrogels, scaffolds, and microparticles for medical applications are considered as a potential opportunity to use bacterial alginate for these applications, taking into account the advantages of biotechnological production of a polymer with desired properties. The methods of producing different alginate-based biomaterials, the manufacturing of implantable medical devices using them, and the surgical techniques for bone and cartilage tissue regeneration using these materials for orthopedic purposes are discussed.

Key Words: Bacterial alginate; Alginate; Tissue engineering; Bone; Cartilage; Regeneration; Hydrogels; Azotobacter; Pseudomonas; Wound

Core Tip: The mini-review explores the potential use of alginates produced biotechnologically by bacteria of genus Azotobacter and Pseudomonas for the development of various implantable hydrogel biomaterials intended for bone and cartilage tissue regeneration and wound healing in orthopedics.

INTRODUCTION

Hard tissues such as bone and cartilage play vital roles in the body by providing support, protecting organs and enabling movement[1]. Bone facilitates communication through muscle contraction, while cartilage cushions joints during movement[2,3]. Due to these crucial functions, regenerating bone and cartilage tissue presents a significant challenge in the fields of tissue engineering, regenerative medicine and orthopedics, as defects resulting from injury, disease and ageing affect millions of people every year. Despite their importance, bones have limited self-healing abilities and regenerating large bone defects remains difficult[4,5]. Cartilage also heals poorly due to low metabolic activity, a lack of blood supply and limited access to nutrients[6]. Therefore, new approaches are required to heal critical bone and cartilage defects and restore their functions. This issue is of great interest to the global orthopedic community due to high clinical demand.

One promising approach involves using exopolysaccharides as scaffolds for repairing bone and cartilage[7]. These biocompatible and biodegradable substances mimic the extracellular matrix (ECM), providing temporary mechanical support and making them ideal for tissue engineering[8]. Alginate, in particular, has gained attention as a key material for regenerating both bone and cartilage thanks to its gelling properties (Figure 1). It is an unbranched polysaccharide consisting of two monomers: Β-D-mannuronic acid and α-L-guluronic acid. These monomers form polymer chains of different lengths via 1-4 glycosidic bonds[9,10]. Interest in using alginate as a biomaterial for bone and cartilage regeneration mainly stems from its ionotropic gelation properties[11]. Its ability to gel in the presence of calcium ions is crucial for its use in various industries, including food, pharmaceuticals, and cosmetics (Figure 2)[12]. The basic principle of ionotropic gelling involves guluronic residues in the alginate binding to Ca²⁺ to form an egg-box structure[13]. This enables alginate chains containing guluronic units to aggregate and form hydrogels, which can be employed as thickeners, stabilizers, emulsifiers, gelling agents, and film formers[14].

Figure 1 Number of publications in the PubMed database from 2000 to 2024. A: Studies on bone repair using alginate as the main biomaterial; B: Studies on cartilage restoration (joints) using alginate as the main biomaterial.

Figure 2  The current application of alginate in various fields.

Currently, all alginate used in the food, pharmaceutical, perfume, cosmetic and medicinal industries is obtained from marine brown algae[15,16]. However, bacterial alginate has several advantages over algal alginate and could be used in a wider range of applications. In this minireview, we will demonstrate the advantages of bacterial alginate over algal alginate and explore its potential application in orthopedics as a hydrogel biomaterial.

ALGAL VS BACTERIAL ALGINATE

By the 2020s, the alginate market was worth around 10 billion dollars[17]. Currently, alginate is only produced commercially from brown algae[18]. However, there are disadvantages to obtaining alginate from algae. Firstly, the chemical composition of synthesized alginate chains depends on the metabolic needs of the organisms producing them. These needs are associated with changes in external conditions, such as seasonal changes, different development cycles and the time at which they are collected. Therefore, it is impossible to ensure quality control in the production of raw materials[19]. Secondly, the extraction process itself involves rough processing (acid or alkaline extraction), which leads to alteration (β-elimination) and partial destruction of the final product. In contrast, producing alginate from microorganisms such as Azotobacter bacteria involves controlled synthesis under laboratory conditions, ensuring consistency of production. One of our previous studies demonstrated the optimization of the alginate synthesis process by the Azotobacter vinelandii 12 bacterial strain. Three parameters that directly affect biopolymer metabolism were varied to maximize alginate production: Sucrose and phosphate concentrations in the medium, and the level of aeration (Figure 3)[10]. As shown in Figure 3, the alginate synthesis metabolic pathway consists of a cascade of enzymatic reactions. These begin with the algD dehydrogenase reaction, followed by alg8 chain polymerization[20-22], and end with the various MM modifications by acetylase complexes and epimerization. During this process, mannuron residues are converted to guluron residues[23-25]. The expression of all genes encoding enzymes of alginate synthesis can be directly regulated by external conditions such as the concentration of substances in the growth medium or the level of aeration[10]. Thus, in our laboratory, we were able to optimize the synthesis of bacterial alginate by the Azotobacter vinelandii 12 bacterium and obtain alginates with defined physicochemical properties, such as molecular weight (MW), M/G composition, and acetylation level, by cultivating and extracting the polymer under certain conditions[10,12]. The isolation and purification process (in our laboratory) for the polymer is also carried out under milder conditions, without the use of strong acids or alkalis. Initially, the bacterial biomass is dissolved in a strong ionic 1 M NaCl solution containing EDTA as a cation chelator. After centrifugation, the resulting supernatant is precipitated with alcohol to form a precipitate, which is then dried by lyophilization. The resulting dry precipitate is then purified by dissolution in a 1 M NaCl solution, followed by dialysis against 1 L of 0.1 M NaCl at 4 °C for 24 hours[10]. The purified bacterial alginate was much cleaner than commercial alginate from algae by further analysis of its chemical structure and assessment of cytotoxicity. Thirdly, bacterial alginate has unique physicochemical properties and improved functional characteristics, unlike algal alginate. The key difference is that bacterial alginate contains O-acetylated groups in the C2 and C3 positions of the mannuronic acid residues in the alginate chain[26]. This arrangement of acetyl groups improves the polymer's mechanical-viscosity properties and affects the interaction of calcium ions and the activity of mannuronate epimerase and mannuronate lyase enzymes[27]. Therefore, bacterial alginate has greater potential for use in various fields than algal alginate, particularly in orthopedics, where strong hydrogel polymers are important.

Figure 3  The metabolic pathway of alginate biosynthesis.

ALGINATE IN ORTHOPEDICS

Biomaterials based on alginate for bone tissue regeneration

Over the past five years, the number of studies on alginate as a biomaterial in the form of hydrogels, scaffolds or microparticles for bone repair has grown exponentially. The advantages of alginate gels include their ability to conform to irregularly shaped bone defects, the ease with which various cellular growth factors can be released, and the ease with which ligands can be attached to them, as demonstrated by peptide motif RGD attachment (Figure 4)[28,29].

Figure 4 Alginate-RGD hydrogels. A: Alginate-RGD hydrogel substrate for studying the adhesion of mesenchymal stem cells (MSCs) in 2D; B: Encapsulated MSCs in an alginate-RGD hydrogel for studying their differentiation in 3D.

A large number of alginate-based biomaterials for bone regeneration have been developed and investigated between 2020 and the present day. The most significant results are summarized in Table 1[30-38]. The table summarizes the descriptions of the three most common materials, as determined by studies conducted from 2020 to 2025: Pure alginate, alginate/chitosan (ALG/CHI), and alginate/hydroxyapatite (ALG/HA). As well as describing the materials themselves, the table describes the development of structures based on them, their physicochemical and mechanical properties, and their biological activity. As can be seen from the table, all developed scaffolds, whether pure alginate or alginate-based composite materials, have certain advantages. Garske et al[30] showed that alginate has good mechanical properties, which preserve the high viability of mesenchymal stem cells (MSCs) encapsulated in oxidized alginate porogen and restore a large volume fraction of bone tissue at the defect site. Composite materials, such as ALG/CHI with the addition of eggshell particles or beta-tricalcium phosphate, have significantly improved osteoconductive properties compared to pure polymer[33,34]. Works on creating scaffolds based on ALG/HA with the inclusion of a proteasome inhibitor have a dual therapeutic function: The simultaneous inhibition of tumours and the regeneration of bone defects[38]. This dual functionality is particularly important in cases of tumour-related bone defects or osteosarcoma, where primary and metastatic tumours inevitably arise[39,40].

Table 1 Summary of alginate-based biomaterials for bone regeneration.

Biomaterial	Development of structures (scaffolds)	Physicochemical and mechanical properties	Biological activity	Ref.
Alginate	Scaffold is an oxidised alginate porogen that contains encapsulated mesenchymal stromal cells (MSCs)	On evaluating the mechanical properties, the stiffness of the scaffold was found tobe 403 ± 3.0 kPa	The in vivo results of cell regeneration and migration showed that the defect area with scaffold had a higher number of cells. (lymphocyte-like and non-lymphocyte-like) compared to pure alginate hydrogel	[30,31]
	Hydrogel construction consisting of photocrosslinked, oxidised and methacrylated alginate	The chemical structure was confirmed using H¹-NMR and FTIR methods. Mechanical testing showed that the elastic modulus of the hydrogel containing 13.55% oxidised alginate was 1315.30 Pa ± 220.77 Pa	In vitro evaluation of the proliferation and osteogenic differentiation of BMMSCs showed that the hydrogel containing the most oxidised alginate produced the weakest results
ALG/CHI	3D-printing of ALG/CHI scaffold followed by impregnation with extract CQ	Mechanical properties showed that shear curves decreased with increasing velocity for all ALG/CHI samples. Evaluation of morphology demonstrated that the scaffolds had an average fibre diameter of 845.73 ± 66.96 μm, a pore size of 357.66 ± 34.78 μm and a contact wettability angle of 42.1° ± 0.7°	Evaluation of antioxidant activity showed that the SA/CHI/CQ scaffold produced the best results (23.00% ± 1.33%). Biocompatibility evaluation demonstrated that the survival rate of the Saos-2 cell line on the SA/CHI/CQ scaffold was higher than on the bare ALG/CHI scaffold	[32-34]
	ALG/CHI scaffold with embedded EPs	The porosity of the scaffold was 89% ± 5%, and the compressive modulus was 3.69 ± 0.70 kPa	Retention and viability of MSCs on the scaffolds showed: 53% ± 12% of cells were retained and 67% ± 17% of these were viable after 21 days
	Composite ALG/CHI/β-TCP scaffold were dissolved and mixed together followed by lyphiolization	The complex shear modulus of the scaffold was greater than 10 kPa at an angular frequency greater than 100 rad/s	In vivo results showed over 23% bone formation in relation to the defect area after 4 weeks and over 60% after 8 weeks with the melatonin-included scaffold
ALG/HA	A lyophilised scaffold based on hydroxyapatite nanoparticles in a gelatin/polyvinyl alcohol/alginate matrix	The hybrid scaffolds exhibited an ultimate compressive strength of 1.1 MPa and a porosity of 70% ± 9.2%	The scaffolds exhibited excellent antibacterial activity against strains of S. epidemidis and E. coli and showed zones of inhibition with diameters of 41.8 ± 0.1 mm and 41.5 ± 0.1 after 24 hours, respectively	[35-38]
	A PHB/HA/ALG scaffold seeded with MSCs	The porosity of the PHB/HA scaffolds was 88% ± 6% and the pore size was 104 ± 25 μm. The physicochemical and mechanical properties of the PHB/HA/ALG scaffold were as follows: Young's modulus - 178.5 ± 1.8 kPa and water absorption - 241% ± 21%	In vivo studies showed that scaffold seeded with MSCs exhibited better regenerative properties compared to other materials
	3D printing using bioink, ALG/GG/HA	The bioinks exhibited linear viscoelastic behaviour, with G′ being greater than G″ up to 100% strain	Evaluation of the viability of SaOs-2 cell line on different bioinks showed that the ink with lower HA content (1%) had a higher number of live cells at all time points
	An ALG/nHA composite hydrogel incorporating the proteasome inhibitor bortezomib has been developed	The water absorption of the composite scaffold was more than 1100% after 24 hours. The compression stress-strain curves of the scaffold had significantly higher values compared to pure alginate	The survival of MC3T3 cells decreased as the concentration of nucleosome inhibitor increased; in vitro and in vivo experiments showed that scaffolds have a pronounced antitumor effect

BMMSCs: Bone marrow mesenchymal stromal cells; ALG/CHI: Alginate/chitosan; CQ: Cissus quadrangularis; EPs: Eggshell particles; ALG/CHI/β-TCP: Alginate/Chitosan/Beta-tricalcium phosphate; MSCs: Mesenchymal stem cells; ALG/HA: Alginate/Hydroxyapatite; PHB/HA/ALG: Poly(3-hydroxybutyrate)/Hydroxyapatite/Alginate; ALG/GG/HA: Alginate/Gellan gum/Hydroxyapatite; ALG/nHA: Alginate/nanohydroxyapatite; E. coli: Escherichia coli.

In addition to the three aforementioned biomaterials, significant research has been conducted on alginate/gelatin and alginate/collagen hydrogel-based bone defect repair in recent years. To enhance the mechanical properties of the hydrogel, El-Bahrawy et al[35] developed a mixture of alginate and methacrylyol gelatin (GelMA), which was cross-linked using ultraviolet light. CaCO₃ and D-(+)-glucono delta-lactone (GDL) were then encapsulated within the developed hydrogel system. Adding methacrylate to the gelatin's chemical structure increased the stiffness of the final alginate and gelatin methacryloylamide (ALG/GelMA) hydrogel, giving it a Young's modulus of 68.37 ± 4.99 kPa after seven days. This high mechanical performance of the material influences the osteogenic phenotype of the MSCs. The indices of alkaline phosphatase activity were therefore highest in the group where the cells were cultured with ALG/GelMA hydrogels containing encapsulated CaCO₃ and GDL particles. In vivo experiments also demonstrated significantly better calvaria regeneration performance by this group in Sprague-Dawley rats[41]. Other studies in which the main biomaterial used to construct the scaffolds is alginate/gelatin have also demonstrated superior viscoelastic properties to classical hydrogels, promising biocompatibility results in vitro and in vivo, and regenerative properties in the osteogenic direction[42-45]. Thus, Miao et al[44] demonstrated the effectiveness of a 3D-printed alginate/gelatin hydrogel scaffold incorporating strontium ranelate particles (SR, 0.5 wt%) in healing skull defects in rats. Alginate/gelatin hydrogels can also act as drug or active agent carriers for bone regeneration. For example, in a recent study, Chinese scientists loaded vascular endothelial growth factors (VEGF) and bone morphogenetic protein-2 (BMP2) into ALG/GelMA microspheres[46]. The microspheres demonstrated good antibacterial properties and the ability to release drugs, while VEGF and BMP2 effectively stimulated angiogenesis and bone tissue repair[46].

The study of alginate/collagen hydrogels also shows great promise in the field of bone regeneration. A considerable number of publications are devoted to the release of strontium and other active substances from various alginate/collagen hydrogel modifications for bone tissue regeneration[47-49]. For example, Tharakan et al[48] demonstrated that such scaffolds exhibited a proliferative effect and osteoinductive properties at low concentrations of strontium calcium polyphosphate. In summary, it can be concluded that alginate-based biomaterials, from which composites, scaffolds and matrices are developed, have been widely used in bone tissue regeneration in recent years. This makes alginate a leading candidate for use in orthopedics in the future. However, it is worth noting that, the bacterial alginate has better physicochemical and mechanical properties than algal alginate, no studies have yet been conducted on its use in bone regeneration. Whereas, the biotechnological method makes it possible to obtain a polymer with a widely adjustable MW and monomeric composition, and, accordingly, mechanical properties, for example, to obtain alginates from which high-strength scaffolds for orthopedics can be manufactured. Therefore, studying bacterial alginate in bone regeneration is highly valuable in orthopedics and biomedicine in general.

Biomaterials based on alginate for cartilage tissue regeneration

Fewer studies have been conducted on cartilage regeneration using alginate than on bone regeneration. However, alginate is well suited as a basic material for cartilage joint healing due to its ability to form hydrogels and its similar mechanical properties. Cartilage is also a notable tissue, as it covers the ends of articulating bones in synovial joints and is a specialised tissue mainly composed of chondrocytes that produce a dense ECM[50]. The degradation of the ECM accompanying articular cartilage damage leads to common clinical problems[51]. Due to its biocompatibility, high water content and adjustable viscosity, alginate as a biomaterial is similar in its properties to ECM. It can therefore not only mimic ECM at the site of articular cartilage damage, but also be used as a complete scaffold for loading cells, active substances and drugs[52].

In recent years, injectable alginate-based hydrogels have become one of the most common approaches to cartilage joint healing[53-57]. All of these studies have a similar experimental design involving the following three steps: (1) The development of an alginate-based hydrogel; (2) The incorporation of active agents, such as adipose-derived stem cells (ADSCs) or 4-octylitaconate, into the composite hydrogel; and (3) The injection of the developed scaffold into the site of cartilage joint injury (Figure 5). For example, in Liao et al's study on the injection of alginate/gelatin microspheres containing ADSCs into the site of femoral trochlear cartilage injury in rats, it was demonstrated that the alginate/gelatin microspheres containing ADSCs produced superior cartilage healing results[54]. This was primarily evident in the fact that, 12 weeks after surgery, the defect site was almost completely filled with cartilage-like tissue, in contrast to the other experimental groups. There were also significantly higher scores on the International Cartilage Repair Society (ICRS) scale[58] and the modified Wakitani scale[59] in the alginate/gelatin group with ADSC inclusion[54]. Similarly, in related work by Chinese scientists, naringenin, a compound from the flavonoid group, was loaded into the alginate/bioglass hydrogel as the active ingredient instead of cells[57]. The results showed that the hydrogel scaffold with naringenin had better performance in both the ICRS and the histological evaluation of the cartilage repair model[57].

Figure 5  This is a summary of the development and application of alginate-based biomaterials as injectable hydrogels for cartilage regeneration.

In cartilage tissue engineering using alginate polymer, in addition to injected polymers, 3D printed engineering technologies are being actively developed in order to fabricate complete artificial cartilage[60,61]. A wide range of polymers with different physicochemical properties, such as chitosan[62], polyurethane[63], poly-ε-caprolactone[61], and others[64-66], are used for 3D printing in combination with alginate. These 3D scaffolds, developed using these polymers, meet the mechanical requirements of cartilage tissue (modulus of elasticity E ≈ 300 kPa), as demonstrated by 3D-printed ALG/CHI scaffolds[62]. These scaffolds demonstrated improved swelling and hydrophilicity, as well as good chondrocyte cell attachment and viability in vitro[62]. Another study involved a full in vivo investigation of the implantation of alginate-based 3D scaffolds in animals, in addition to in vitro experiments[65]. The scaffold developed from tempo-oxidized cellulose nanofibre, decellularized ECM and alginate not only demonstrated increased proliferation of bone marrow stromal cells and stimulated chondrogenesis, but also formed a newly formed cartilage-like tissue around itself during in vivo subcutaneous implantation in rats due to its suitable structure[65].

All these results show that alginate has comparable potential for use as a biomaterial in cartilage repair as in bone regeneration for orthopedics. Due to its similar mechanical properties to those of cartilage connective tissue, alginate has high chondrogenic potential, providing cells (chondrocytes) with a natural environment[66]. Thus, alginate, especially that of bacterial origin, has extensive potential in cartilage joint healing in osteoarthritis due to its better physicochemical and mechanical properties, which may provide new insights and treatment approaches in orthopedics.

THE CURRENT STATUS OF BACTERIAL ALGINATE APPLICATIONS IN BIOMEDICINE, WITH A FOCUS ON THEIR POTENTIAL IN ORTHOPEDICS

Despite the rapidly increasing interest in alginate in the field of orthopedics (Figure 1), only a couple of laboratories are currently conducting research on alginate of bacterial origin, not only in orthopedics, but in biomedicine in general.

The first research group to deal directly with the synthesis of bacterial alginate for use in dressings is located in Germany[67,68]. Hoefer et al[67] and Fischer et al[68] demonstrated the synthesis of alginate by the Azotobacter vinelandii ATCC 9046 bacterial strain, which was then used to produce alginate fibres by microextrusion. The physicochemical properties results showed that bacterial alginate had a higher MW than algal alginate and a higher degree of acetylation[67]. In summary, the gel dressings formed were stable hydrogels of sufficient shape and strength for wound healing. In vitro results showed that alginate bacterial dressings reduced the concentration of the pro-inflammatory cytokines TNF-α and IL-8[68]. Furthermore, microbial alginate was found to bind significantly more elastase and matrix metalloprotease-2 than marine alginate dressings[68]. Thus, German scientists have demonstrated that, as a biomedical material, microbial alginate has more advantages than seaweed alginate.

Our group is investigating the synthesis of bacterial alginate and its potential applications in different fields of medicine, including orthopedics, in parallel to a group of German scientists. For example, we have investigated the physicochemical properties of synthesized alginates produced by the bacterium Azotobacter vinelandii 12 by adjusting the cultivation conditions of these bacteria[10]. An evaluation of the physicochemical and mechanical properties showed that the microbial alginate had higher values for MW, viscoelasticity, water absorption, and gel formation than the algal alginate[10]. In vitro cytotoxicity evaluation on MSCs showed that both alginates (bacterial and algal) exhibited minimal cytotoxicity at all time points; however, bacterial alginate had a less negative effect on cell growth[10,69]. In one of our recent studies, we developed a poly(3-hydroxybutyrate) and alginate (PHB/ALG) construct as an intestinal patch for implantation into the large intestine of Wistar rats[70]. The results showed that the bacterial polymer-based PHB/ALG constructs had no adverse effect on the gut microbiota of the animals. This suggests that the PHB/ALG patch may be biocompatible with the gut microbiota. This makes the patch a promising candidate for the future invasive treatment of severe colonic diseases[70]. The possibilities demonstrated in this study of encapsulating live probiotic bacteria in bacterial alginate as part of an implantable scaffold can also be used in orthopedics as an alternative treatment for deep infected wounds, since the use of probiotics for wound treatment has become a promising area in traumatology[71].

The main limitations in the use of bacterial alginate in biomedicine, particularly in orthopedics, lie in the economic aspect and the difficulty of scaling up the synthesis process. As can be seen in Table 2, only two companies are currently producing bacterial alginate: Biosynth in Switzerland and USBiological Life Sciences in the United States. Order volumes are significantly lower than for similar alginate of algal origin because bacterial alginate is synthesized under strictly laboratory conditions in very small amounts. Furthermore, the full cycle of bacterial alginate production-synthesis, process optimization, and multi-stage extraction and purification of the polymer-makes the final cost much higher than that of algal alginate, which is produced on a large scale from harvested seaweed by rough extraction with alkalis or acids. It should also be noted that to obtain algal alginate of medical grade, a very complex and expensive purification procedure is required, without which alginate has increased cytotoxicity, which prevents its use for bone tissue engineering[72]. To obtain biocompatible bacterial alginate from biomass of Azotobacter sp. a much simpler cleaning procedure is required[10,69,70].

Table 2 Comparative costs of alginate produced by different companies from algae and bacteria.

	Volume, g	Cost, $	Manufacturing companies
Bacterial	5	950-1150	Biosynth (Switzerland), USBiological Life Sciences (United States)
Algal	25	≈ 18	Flinn Scientific (Canada), Carolina Biological Supply (United States)
	500	70-270	Merck (Germany), Snow Sea (Russia), Fisher Scientific International, Inc. (United States)
	1000	125-550	Merck (Germany), MSK Ingredients (United Kingdom), Fisher Scientific International, Inc. (United States)

Nevertheless, it should be acknowledged that the use of bacterial alginate in orthopedics may face the risk of immunogenicity due to the admixture of endotoxin if the technique of its removal is not well established. In addition, it is a completely new biomaterial, therefore, its certification, standardization, a full cycle of preclinical and clinical studies, industrial implementation, and regulatory approval will be required, which also takes time and carries risks for its introduction into clinical practice[73].

Nevertheless, the previous sections considered the use of algal alginate and various scaffolds based on it in orthopedics, and the results showed that alginate is a biocompatible polymer. This was demonstrated by the in vitro cytotoxicity test and in vivo tissue reaction, as well as by its biological activity-namely, the ability of cells to undergo osteogenic and chondrogenic differentiation in the presence of the alginate polymer. The results of our research group[10,12,69,70] and German scientists[67,68] showed that bacterial alginate is comparable to and superior to algal alginate in all respects: Physicochemical properties (MW, acetylation), mechanical properties, biocompatibility and proliferation.

Despite the limitations of scalability and economics, only a biotechnological method for producing alginate can provide the manufacturing of unique brands of medical grade alginate for use in orthopedics, e.g. alginate with an extremely high MW, high level of acetylation and desired M/G ratio. Such alginate has enhanced mechanical properties suitable for the manufacture of scaffolds and implants for the regeneration of bone and cartilage tissues while simultaneously replenishing mechanical properties due to damage to bone and cartilage[74]. Microbiological synthesis will also make it possible to create special brands of medical alginate with strictly defined properties for obtaining scaffolds and implants for orthopedics from it using rapid prototyping and electrospinning technologies[75].

This suggests that new approaches and strategies for invasive techniques in orthopedics can be developed based on highly purified microbial alginate, due to its superior qualities.

CONCLUSION

Different products in the form of hydrogels, scaffolds, and microparticles based on algal alginate and its composites with other biomaterials are increasingly used for bone and cartilage repair in orthopedics. The most important advantage of the biotechnological method of alginate production using controlled biosynthesis is the ability to obtain a polymer with specified properties, which is independent of marine weather conditions, climate change and environmental pollution, as in the case of algal alginate production. With good purification technology, this will allow the production of alginate biomaterials of medical grades, in particular, alginate biomaterial grades for various applications in orthopedics.

ACKNOWLEDGMENTS

Supported by Russian Science Foundation, No. 23-74-10027 in part of Section “ALGINATE IN ORTHOPEDICS”), and was carried out within the framework of government assignment of the Ministry of Science and Higher Education of the Russian Federation in all other parts.