Biomaterials either synthetic or natural based materials are widely used in various biomedical applications which to replacing damaged tissue or enhancing biological properties of human skeleton system. The past decade several researchers have been focused naturally derived biopolymer products with unique physicochemical properties and highly biocompatibility, biodegradability and non-toxic materials for drug delivery, biomedical and industrial applications (Raus et al., 2021; Reakasame and Boccaccini, 2018). Among them, the worldwide alginate is the abundant biopolymer major source of marine environmental and other cellulose materials. Sodium alginate is major contains of alginic acid, potassium, calcium, ammonium salts and propylene glycol alginate (Li et al., 2017). Those biomolecules is a very important biomedical application of wound healing, bone tissue engineering and cell culture. Alginates are mainly extracted from brown algae-cell membranes including Macrocystispyrifera, Lessonia, Ascophyllumnodosum, Laminaria Hyperborean, Sargassum, DurvilleaEclonia and also be produced bacterial species of Pseudomonas, Azotobactervinelandii(Szekalska et al., 2016). Which alginate contains up to 40% of their dry weights. Alginate is two disparate compositions contains of M-blockand G-block, that major backbone of their physicochemical properties, such as transformation of thesol /gel and water absorption as well as viscosity. The alginate polymer is viscosity depending on the pH of the solution, if pH value increasing which causes of decreasing in the viscosity due to their protonation of the carboxylate groups in the alginate. In commercial molecular weight of the sodium alginates have average between 33,000 and 400,000 g/mol (Watthanaphanit et al., 2018). The alginate is higher molecular weight based prepared materials had more viscous and an excellent gel forming properties. Alginates most considered due to the important biological properties of non-toxic, biocompatible and non-immunogenic (Fig.1). In this review, disused alginate based composite to be used for various recent biomedical applications in wound healing, tissue
Figure 1 Advantage of alginate
- Biomedical applications
2.1. Wound healing
In human skeleton has largest sensor system of skin and its play an important role of protection from the microbes, environmental factors, and also maintains electrolytes, body fluid and nutritional components. Wounds are defined based on the disruption of skin integrity and their function which leads to different causes such as surgery, trauma, burns and diabetes (Xu et al., 2015). Wound healing process is common in human life. But in current scenario healing process is difficult based on wound is acute or chronic. Moister based wound healing materials are potentially enhancing, the cells and enzymes, and also accelerates the proliferation of tissue its leads to promote wound healing. Wound healing dressing materials should be exhibiting the following characteristics: (1) fist stop blood bleeding and relief the pain; (2) absorb exudate body fluid and maintain wound moister environment; (3) easily to rejoining of health tissues; (4) gas permeability and good water vapor; (5) reduce the infection from the microbial contamination; (6) enhancing the formation of re-epithelialization and granulation rate; (7) most important of nontoxic and biocompatible of the prepared materials (Liang et al., 2019; Miguel et al., 2019). Most promising material of alginate is potential used for wound dressing development in the form of hydrogel, film, beads and forms, in this based materials good biological and physicochemical properties such as nontoxicity, biodegradability, excellent water absorption capacity, non-immunogenicity and hemostatic property (Rajpooot and Jain, 2020; Niu et al., 2019; Okur et al., 2019). Table 1 revealed recent literature of alginate based biomaterials for wound healing activity.
2.2. Tissue engineering
Tissue engineering is more important in biomedical field its tool for restoring or improving tissue or organs at specific defective area. Alginate based hydrogel can be synthesized different cross-linking techniques such as covalent crosslinking, ionic crosslinking, cell crosslinking, phase transition and free radical polymerization and its structure similar to extracellular matrices of living tissues (Costa et al., 2018; Lee et al., 2012; Tan and Marra, 2010). In currently more research emphasis is given in the field of tissue engineering, towards the healing of the damaged or injured tissues. Naturally bone tissue has greater ability to reconstruct of small damage, but large bone defects are required some additional treatment. Several critical bone diseases like bone cancer, osteoarthritis, osteoporosis, bone infection and major bone fracture it’s also needed extra treatment for complete
Table 1 Alginate based composite materials for wound dressing
|Alginate + gelatin
||Diniz et al., 2020
|Alginate + Chitosan
|Wrona et al., 2016
|Alginate + Activated charcoal
||Moisture absorbent wound
||Osmokrovic et al., 2019
|Alginate + Vancomycin
||Kurczewska et al., 2017
|Alginate + Nano – hydroxyapatite
||Zhang et al., 2017
|Alginate + Natural polyols (polypropylene
properties of dressing sheets
|Namviriyachote et al., 2019
|Alginate + Collagen @ polyacrylamide
|Mix with oxidized sodium alginate
as a new cross linker (COA) to formcomposite hydrogel
|Bai et al., 2018
|Alginate + Chinese nutgall
||Xue et al., 2019
|Alginate + Zinc ions (Zn2+)
||Osmokrovic et al., 2019
|Alginate + Poly (lactic-co-glycolic acid) Manuka honey
||Properly release ofoxygen to cells and tissues
||Nanm, et al., 2018
|Alginate + Silver nanoparticles (Ag NPs) and
||Namviriyachote et at., 2019
|Alginate + Halloysite nanotubes
||Kurczewska et al., 2017
|Alginate + gelatin + polyvinyl alcohol
||Maintain wound moistenvironment and absorb exudates and enhance interactionwith the tissues
||Satish et al., 2019
|Alginate + PVA + PVP
||Proliferation and adhesive properties
||Jin et at., 2016
Table 2 Alginate based composites for tissue engineering
|Vascular of adiposetissue
||Enhancing revascularization of adipose tissue when combinationof VEGF + alginatewith adipocytes.
||Ding et al., 2015
||Good development of left ventricular function in rats, Alginate hydrogel form.
||Rocca et al., 2016
||Improvement of stromal vascular function. 3D alginate spheroid combined with with humanfat-derived stromal vascular.
||Williams et at., 2013
||Propagating of epithelial therapeutic in cornea
||Wright et al at., 2012
||Proliferation of encapsulated HepG2/C3A liver cells for in vivo implantation
||Capone et al., 2013
||Promotes and proliferation of chondrocyte andchondrogenic phenotype.
||Mhanna et al., 2014
||Improved testicular tissue, the grafted combined with alginate hydrogel.
||Poels et al., 2016
Table 3 Alginate based composites for drug delivery
||Anticancer drug delivery
||Liu et al., 2017
||Enhance chemotherapeutic for colon cancer
||Hosseinifar et al., 2018
|Alginate+ Magnetic Alginate/Chitosan
||Sustained drug release and enhancing cytotoxicity against Human breastcancer.
||Sang et al., 2018
|Alginate+ Folate conjugated hyaluronic acid coatedalginate
|Antitumor and apoptosis activity against on coloncancer therapy.
||Shad et al., 2019
||Potential anti-tumor agent for breast cancer.
||Sun et al., 2017
|Alginate nanogel platform
||Inhibit tumor growth of breast cancer and improved life of cancerpatients.
||Enhance chemotherapeutic for Human tongue carcinoma.
||Shtenberg et al., 2018
|Alginate-PAMAM (G5) hybrid nanogel
||Reduced toxic and improvement of anticancer activity against Human breastcancer
||Matai et al., 2016
|Dual crosslinkedmethacrylated alginate(Alg-MA)
||Best anticancer activity of Human lungepithelial carcinoma cells.
||Chen et al 2014
|Chitosan-alginatepolyelectrolytemultilayer capsule filled with bovine
serum albumin gel (BSAgel-capsule
|An excellent efficacy of drug resistant breast cancer.
||Shen et al 2018
||Potential improves against for colon cancer.
||Dodov et al 2013
recovery of bone tissue (Kurowiak et al., 2020; Urtuvia et al., 2017). Alginate incorporated biomaterials are commonly used as a potential therapeutic agents for pain relieving, anti-inflammatory and along with anti-microbial. Alginate based hydrogels are attractive in wound healing, drug delivery and tissue engineering because of chemical structural similarity to the extracellular matrices in human tissues.
2.3. Drug delivery
Ensuring lowest therapeutic dosing molecules reaching to specifically targeted tissue or organ with minimum side effects and maximum effectiveness of thedrug it’s the major objective of the drug delivery system (Chawla et al. 2017). The generally drug delivery method has been through the oral route, administered orally, prolonged-release drug, face two challenges, an unpredictable rate of gastric emptying and short gastric residence time. Several method and material have been developed and tested for drug delivery applications. Among them, alginate based hydrogel has been most attractive because the easily gelation process it’s mainly used for sustained drug release and cell encapsulation. In current researchers have been reported several alginate based hydrogel drug delivery system for wound dressing applications (Tsujimotoet al., 2018). Table 3 showed current research reported of alginate based hydrogel or composite for drug delivery applications.
Alginates are natural biopolymer derived from various biological resources of marine algae and some other microbial sources, which have been traditionally, used many industrial applications of pharmaceutical, wound dressing, tissue engineering and drug delivery. Alginate based hydrogel materials possess good physicochemical properties such as nontoxicity, biocompatibility, biodegradability and excellent viscosity. In moreover, alginate incorporated films, beads, fibers, forms and hydrogel are also to be performed in vitro and in vivo studies its revealed exhibit cell proliferation of tissue, hemostatic and antibacterial activity have been reported pervious several researchers. In this review suggested alginate based hydrogel biomaterials are currently developed many promise materials and thus need to provide new approaches for treatment of biomedical applications in future options.
Funding: The authors received no specific funding for this work.
Conflicts of Interest: None
- Bai, Z., Dan, W., Yu, G., Wang, Y., Chen, Y., Huang, Y. Tough and tissue-adhesive polyacrylamide/collagen hydrogel with dopamine-grafted oxidized sodium alginate as crosslinker for cutaneous wound healing. RSC Adv 42 (2018) 23–32.
- Capone, S.H., Dufresne, M., Rechel, M., Fleury, M.J., Salsac, A.V., Paullier, P., Impact of alginate composition: from bead mechanical properties to encapsulated HepG2/C3A cell activities for in vivo implantation. PLoS One. 8 (2013) e62032.
- Chawla, G., Gupta, P., Bansal, A. Gastroretentive drug delivery system. In Progress in Controlled and Novel Drug Delivery; Jain, N.K., Ed.; CBS: New Delhi, India, (2004) 76–97
- Chen, Z. C., Fillmore, M. P., Hammerman, S. Kim, C.F., Wong, K.K., Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer. 14 (2014) 535.
- Costa, M., Marques, A., Pastrana, L., Teixeira, J., Sillankorva, S., Cerqueira, M. Physicochemical properties of alginate-based films: Effect of ionic crosslinking and mannuronic and guluronic acid ratio. Food Hydrocoll. 81 (2018) 442–448.
- Ding, S.L., Zhang. M.Y., Tang, S.J., Yang, H., Tan. W.Q, Effect of calcium alginate microsphere loaded with vascular endothelial growth factor on adipose tissue transplantation. Ann. Plast. Surg. 75 (2015) 644–51.
- Diniz, F., Maia, R., Rannier, R., Andrade, L., Severino, L. N. Silver nanoparticles-composing alginate/gelatine hydrogel improves wound healing in vivo, Nanomaterials (Basel), 23 (2020) 390.
- Dodov, M. G., Steffansen. B., M. Crcarevska, S. N. Geskovski, S. Dimchevska, Kuzmanovska, Goracinova, S.K. Wheat germ agglutinin-functionalisedcrosslinked polyelectrolyte microparticles for local colon delivery of 5-FU: in vitro efficacy and in vivo gastrointestinal distribution. J. Microencapsul. 643 (2013) 56.
- Hosseinifar, T. S., Sheybani, M., Abdouss, S.A.H., Najafabadi., Ardestani, M.S, Pressure responsive nanogel base on alginatecyclodextrin with enhanced apoptosis mechanism for colon cancer delivery. J Biomed Mater Res A. 106 (2018) 349–59.
- Jin, S.G., Kim, K.S., Kim, D.W., Kim, D.S., Seo, Y.G., Go, T.G., Youn, Y.S., Kim, J.O., Yong, C.S., Choi, H.G, Development of a novel sodium fusidate-loaded triple polymer hydrogel wound dressing: mechanical properties and effects on wound repair. Int. J. Pharm. 497 (1–2) (2016) 114–122.
- Kurczewska, J., Pecyna, P., Ratajczak, M., Gajecka, M. G. Schroeder, Halloysite nanotubes as carriers of vancomycin in alginate-based wound dressing. Saudi Pharm J. 25 (2017) 911–20.
- Kurczewska, J., Pecyna, P., Ratajczak, M., Gajecka, M., Schroeder. G, Halloysite nanotubes as carriers of vancomycin in alginate-based wound dressing. Saudi Pharm J. (2017)25 911–20.
- Kurowiak J, Kaczmarek-Pawelska A, Mackiewicz AG, Bedzinski R. Analysis of the degradation process of alginate-based hydrogels in artifcial urine for use as a bioresorbable material in the treatment of urethral injuries. Processes 8 (2020) 304–315
- Lee, K. Y., Mooney, D. J. Alginate: properties and biomedical applications. ProgPolym Sci. 37 (2012) 106–26.
- Li, X., Jiang, Y., Wang, F., Fan, Z., Wang, H., Tao, C., Wang, Z. Preparation of polyurethane/polyvinyl alcohol hydrogel and its performance enhancement via compositing with silver particles, RSC Adv. 73 (2017) 46480–46485.
- Liang, M., Chen, Z., Wang, F., Liu, L., Wei, R., Zhang, M. Preparation of self-regulating/ anti-adhesive hydrogels and their ability to promote healing in burn wounds, J Biomed Mater Res B ApplBiomater 107 (2019) 1471–1482.
- Liu, M., Song, X., Wen, Y., Zhu, J.L., Li, J, Injectable thermoresponsive hydrogel formed by alginate-gpoly (N isopropylacrylamide) that releases doxorubicin-encapsulated micelles as a smart drug delivery system. ACS Appl Mater Interfaces. 9 (2017) 35673–82.
- Matai, I., Gopinath, P,.chemically cross-linked hybrid nanogels of alginate and PAMAM dendrimers as efficient anticancer drug delivery vehicles. ACS BiomaterSci Eng. 2 (2016) 213–23.
- Mhanna, R., Kashyap, A., Palazzolo, G., Martin, Q.V., Becher, J. S., Moller, Chondrocyte culture in three-dimensional alginate sulfate hydrogels promotes proliferation while maintaining expression of chondrogenic markers. Tissue Eng Part A. 20 (2014) 1454–64.
- Miguel, S. P., Moreira, A. F., Correia, I. J. Chitosan based-asymmetric membranes for wound healing: a review, Int. J. Biol. Macromol. 127 (2019) 460–475
- Mirrahimi, M. Z., Abed, J., Beik, I., Shiri, A., Dezfuli, V., Mahabadi, S.S., Kamrava, H., Ghaznavi, A.S., Zadeh, A thermo-responsive alginate nanogel platform coloaded with gold nanoparticles and cisplatin for combined cancer chemophotothermal therapy. Pharmacol Res. 143 (2019) 178–85.
- Namviriyachote, N., Lipipun, Akhawattanangkul, V. Y., Charoonrut, P., Ritthidej, G.C., Development of polyurethane foam dressing containing silver and asiaticoside for healing of dermal wound. Asian J Pharm Sci 14 (2019) 63–77.
- Namviriyachote, N., Lipipun, V., Akkhawattanangkul, Y., Charoonrut, P., Ritthidej, G.C, Development of polyurethane foam dressing containing silver and asiaticoside for healing of dermal wound. Asian J Pharm Sci.14 (2019) 63–77.
- Nanm, A., Kam. A Influence of manuka honey on mechanical performance and swelling behaviour of alginate hydrogel film. IOP ConfSer Mater Sci Eng. 440 (2018) 012024.
- Niu, B., Jia, J., Wanga, H. Chen, S., Cao, W., Yan, J., Gong, X., Lian, X., Li, W., Fan, Y. In vitro and in vivo release of diclofenac sodium-loaded sodium alginate/carboxymethyl chitosan-ZnO hydrogel beads. Int. J. Biol. Macromol. 141 (2019) 141, 1191–1198.
- Okur, N. U., Hökenek, N., Okur, M., Ayla, S., Yoltas, A., Siafaka, P., Cevher, E. An alternative approach to wound healing field; new composite films from natural polymers for mupirocin dermal delivery. Saudi Pharm. J. 27 (2019) 738–752.
- Osmokrovic, A., Jancic, I., Castvan, I. J., Milenkovic, P. P., Obradovic, B, Novel composite zinc-alginate hydrogels with activated charcoal aimed for potential applications in multifunctional primary wound dressings. Hemijska Ind. 73 (2019) 37-46.
- Osmokrovic, A., Jancic, I., Castvan, I.J., Petrovic, P., Milenkovic, M., Obradovic, B. Novel composite zinc-alginate hydrogels with activated charcoal aimed for potential applications in multifunctional primary wound dressings. Hemijska. Ind. 73 (2019) 37–46.
- Poels, J., Ghannam, G.A., Decamps, A., Leyman, M., Rieux, A., Wyns, C, Transplantation of testicular tissue in alginate hydrogel loaded with VEGF nanoparticles improves spermatogonial recovery. J Control Rel 234 (2016) 79–89.
- Rajpooot, K., Jain, S., Oral delivery of pH-responsive alginate microbeads incorporating folic acid-grafted solid lipid nanoparticles exhibits enhanced targeting effect against colorectal cancer: A dual-targeted approach. Int. J. Biol. Macromol. 151 (2020) 830–844.
- Raus, R. A., Nawawi, W. M. F.W., Nasaruddin, R. R. Alginate and alginate composites for biomedical applications. Asian Journal of Pharmaceutical Sciences 16 (2021) 280–306
- Reakasame, S., Boccaccini, A. R. Oxidized alginate-based hydrogels for tissue engineering applications: a review. Biomacromolecules, 19 (2018) 3–21.
- Rocca, D.G., Willenberg, B.J., Qi, Y., Simmons, C.S., Rubiano, A., Ferreira, L.F, An injectable capillary-like microstructuredalginate hydrogel improves left ventricular function after myocardial infarction in rats. Int. J. Cardiol. 220 (2016) 149–54.
- Satish, A., Aswathi, R., Caroline Maria, J., Korrapati, P.S, Triiodothyronine impregnated alginate/gelatin/polyvinyl alcohol composite scaffold designed for exudateintensive wound therapy. Eur. Polym. J. 110 (2019) 252–264.
- Shad, P.M., Karizi, S.Z., Javan, R.S., Mirzaie, A., Noorbazargan, H., Akbarzadeh,.I., Rezaie, H., Folate conjugated hyaluronic acid coated alginate nanogels encapsulated oxaliplatin enhance antitumor and apoptosis efficacy on colorectal cancer cells (HT29 cell line). Toxicol in Vitro. 65 (2019) 104756.
- Shen, H. F., D., Yang, Yang, Z,. Yao, C., Ye,Y,. Li, X.W,. Wang, Wang, D.Z,. Yao, Y. Ye, Wan, X,. Chitosan–alginate BSA-gel-capsules for local chemotherapy against drug-resistant breast cancer. Drug Des DevelTher. 12 (2018) 921.
- Shtenberg, Y., Goldfeder, M. H., Prinz, J., Shainsky, Y., Ghantous, I.A., Naaj, A. Schroeder, H.B. Peled, Mucoadhesive alginate pastes with embedded liposomes for local oral drug delivery. Int J BiolMacromol. 111 (2018) 62.
- Song, W., Su, X., Gregory, D. A., Li, W., Cai, Z., Zhao, X, Magnetic alginate/chitosan nanoparticles for targeted delivery of curcumin into human breast cancer cells. Nanomaterials. 4 (2018) 907.
- Sun Z. Y., Zeng, Z., Huaiying, M., Xiaomin, S., Wen, S., Xiaoyu, X., Bio-responsive alginate-keratin composite nanogels with enhanced drug loading efficiency for cancer therapy. Carbohydr Polym.175 (2017) 159–69.
- Szekalska, M., Puciłowska, A., Szymanska, E., Ciosek, P., Winnicka, K. Alginate: current use and future perspectives in pharmaceutical and biomedical applications. Int J PolymSci (2016) 1–17.
- Tan, H., Marra, K. G. Injectable, biodegradable hydrogels for tissue engineering applications. Materials, 3 (2010) 1746–67.
- Tsujimoto, T., Sudo, H., Todoh, M., Yamada, K., Iwasaki, K., Ohnishi, T., Hirohama, N., Nonoyama, T., Ukeba, D., Ura, K. An acellularbioresorbable ultra-purified alginate gel promotes intervertebral disc repair: A preclinical proof-of-concept study. EBioMedicine 2018, 37, 521–534.
- Urtuvia V, Maturana N, Acevedo F, Peña C, Díaz-Barrera A (2017) Bacterial alginate production: an overview of its biosynthesis and potential industrial production. World J MicrobiolBiotechnol 33(2017)198–208.
- Watthanaphanit A, Supaphol P, Tamura H, Tokura S, Rujiravanit R. Fabrication, structure, and properties of chitin whisker-reinforced alginate nanocompositefbers. J ApplPolymSci 2008;110(2):890–9.
- Williams, S.K., Touroo, J.S., Church, K.H., Hoying, J.B., Encapsulation of adipose stromal vascular fraction cells in alginate hydrogel spheroids using a direct-write three-dimensional printing system. Biores Open Access. 2 (2013) 448–54.
- Wright, B., Cave, R.A., Cook, J.P., Khutoryanskiy, V.V., Mi, S., Chen, B., Enhanced viability of corneal epithelial cells for efficient transport/storage using a structurally modified calcium alginate hydrogel. Regen Med. 7 (2012) 295–307.
- Wrona, M. Wm, Kucharska, M., Struszczyk, M.H., Cichecka, M., Hałgas, B. W., Szymonowicz. M. Hemostatic, resorbable dressing of natural polymers-hemoguard. Autex Res J. 16 (2016) 29–34.
- Xu, R., Luo, G., Xia, H., He, W., Zhao, J., Liu, B., Tan, J., Zhou, Liu, D., Wang, Y., and Wu, J. Novel bilayer wound dressing composed of silicone rubber with particular micropores enhanced wound re-epithelialization and contraction, Biomaterials 40 (2015) 1–11
- Xue, W., Zhang, M., Zhao, F., Gao, J., Wang, L, Long-term durability antibacterial microcapsules with plant-derived Chinese nutgall and their applications in wound dressing. E-Polymers. 19 (2019) 268–76.
- Zhang, X., Huang, C., Zhao, Y., Jin, X, Preparation and characterization of nanoparticle reinforced alginate fibers with high porosity for potential wound dressing application. RSC Adv 76 (2017) 9349–58.