Authors
Drozd N. N.1
Belozerskaya G. G.1
Momot A. P.2
Logvinova Y. S.1
Kabak V. A.1
Nevedrova O. E.1
Barannikova L. V.1
Rossa A. A.1
1National Medical Research Center for Hematology, Russian Federation, Russia
2Altai Branch of the National Medical Research Center of Hematology, Russian Federation, Russia
Corresponding Author
Drozd Natalia; å-mail: drozd.n@blood.ru
Conflict of interest
None declared.
Funding
The study had no sponsorship.
Received
09.09.2025
Abstract
Abstract. Over the past few years, they have been intensively developing new promising nano-, micro-, and macro-dimensional biomaterials containing natural polysaccharides for use in order to eliminate bone tissue damage. The interest of researchers in this field is confirmed by the increasing number of publications every year. Objective. To analyze modern scientific research works devoted to the study of the effect of biomaterials containing natural polysaccharides on the restoration of bone tissue. Materials and Methods. The literature review is based on the analysis of data from databases eLibrary.ru, PubMed, Google Scholar, Scopus. Keywords used for the search: «natural polysaccharides» (native polysaccharides), «biomaterials» (biomaterials), «marine polysaccharides» (marine polysaccharides), «plant polysaccharides» (plant polysaccharides), «glycosaminoglycans» (glycose-minoglycans), «osteoconduction» (osteoconduction), «osteoinduction», «bone regeneration». Query dates are March-May 2025, query depth is 2020-2025. The results. According to the results of the publications, it is shown that the effectiveness of the in vitro and in vivo effects of biomaterials on bone tissue repair is associated not only with natural polysaccharides, the basis of the mold structure, but also with the introduction of biologically active compounds and cells into the structure. The forms of composite biomaterials with natural polysaccharides containing nanoparticles, nanocrystals, fibers, films, membranes, hydrogels, frameworks, sponges and affecting the regeneration of bone tissue are systematized. New experimental data show that the use of natural polysaccharides that mimic the bone matrix as the basis or components of biomaterials is a promising way to stimulate the restoration of bone defects and fractures, which contributes to further research in the field of developing new biomaterials for bone tissue repair. Conclusions. The creation of biomaterials containing natural polysaccharides is a promising direction for the development of therapeutic agents used to increase the efficiency of regeneration of bone tissue defects.
Key words
natural polysaccharides, biomaterials, bone tissue regeneration
DOI
References
1. Rizzo M. G., Briglia M., Zammuto V., Morganti D., Faggio C., Impellitteri F. et al. Innovation in Osteogenesis Activation: Role of Marine-Derived Materials in Bone Regeneration. Curr Issues Mol Biol. 2025;47(3):175. https://doi.org/:10.3390/cimb47030175
2. Žiaran S., Danišovič Ľ., Hammer N. Tissue engineering and regenerative medicine: advances, controversies, and future directions. Front Bioeng Biotechnol. 2025;13:1568490. https://doi.org/:10.3389/fbioe.2025.1568490
3. Jin A., Shao Y., Wang F., Feng J., Lei L., Dai M. Designing polysaccharide materials for tissue repair and regeneration. APL Materials. 2024;12(8): 080601. https://doi.org/:10.1063/5.0223937
4. Lv X., Yu H., Han J., Hou Y., Sun Y., Liu K. et al. Tunicate cellulose nanocrystals reinforced modified calcium sulfate bone cement with enhanced mechanical properties for bone repair. Carbohydr Polym. 2024;323:121380. https://doi.org/:10.1016/j.carbpol.2023.121380
5. Chen X., Wu T., Bu Y., Yan H., Lin Q. Fabrication and biomedical application of alginate composite hydrogels in bone tissue engineering: A review. International Journal of Molecular Sciences, 2024;25(14):7810. https://doi.org/:10.3390/ijms25147810.
6. Mohammed A., Naveed M., Jost N. Polysaccharides; classification, chemical properties, and future perspective applications in fields of pharmacology and biological medicine (a review of current applications and upcoming potentialities). J Polym Environ. 2021;29(8):2359-2371. https://doi.org/:10.1007/s10924-021-02052-2
7. Lekhavadhani S., Babu S., Shanmugavadivu A., Selvamurugan N. Recent progress in alginate-based nanocomposites for bone tissue engineering applications. Colloids Surf B Biointerfaces. 2025;250:114570. https://doi.org/:10.1016/j.colsurfb.2025.114570
8. Xu Q., Zhang Y. Research progress on the bioactivity of compound polysaccharides: A review. Int J Biol Macromol. 2025;306(Pt 3):141693. https://doi.org/:10.1016/j.ijbiomac.2025.141693.
9. Lu D., Zhang Y., Liang S., Li Y., Qing J., Gu L. et al. M2 Macrophages Guide Periosteal Stromal Cell Recruitment and Initiate Bone Injury Regeneration. Biomedicines. 2024;12(6):1205. https://doi.org/:10.3390/biomedicines12061205
10. Dang Y., Zhang Y., Luo G., Li D., Ma Y., Xiao Y. et al. The decisive early phase of biomaterial-induced bone regeneration. Appl Mater Today. 2024;38:102236. https://https://doi.org/:10.1016/j.apmt.2024.102236
11. Oliveira É. R., Nie L., Podstawczyk D., Allahbakhsh A., Ratnayake J., Brasil D. L. et al. Advances in growth factor delivery for bone tissue engineering. Int J Mol Sci. 2021;22(2):903. https://doi.org/:10.3390/ijms22020903
12. Ball J. R., Shelby T., Hernandez F., Mayfield C. K., Lieberman J. R. Delivery of growth factors to enhance bone repair. Bioengineering. 2023;10(11):1252. https://doi.org/:103390/bioengineering10111252
13. Shariati K., Bedar M., Huang K. X., Moghadam S., Mirzaie S., LaGuardia J. S. et al. Biomaterial Cues for Regulation of Osteoclast Differentiation and Function in Bone Regeneration. Advanced Therapeutics. 2025;8(1):2400296. https://doi.org/:10.1002/adtp.202400296
14. Lin X., Patil S., Gao Y. G., Qian A. The bone extracellular matrix in bone formation and regeneration. Front Pharmacol. 2020;11:757. https://doi.org/:10.3389/fphar.2020.00757
15. Ladeira B., Gomes M., Wei K., Custódio C., Mano J. Supramolecular assembly of multi-purpose tissue engineering platforms from human extracellular matrix. Biomaterials. 2025;320:123270. https://doi.org/:10.1016/j.biomaterials.2025.123270
16. Zheng Y., Ke Z., Hu G., Tong S. Hydrogel promotes bone regeneration through various mechanisms: a review. Biomed Tech (Berl). 2024;70(2):103-114. https://doi.org/:10.1515/bmt-2024-0391
17. Salbach-Hirsch J., Rauner M., Hofbauer C., Hofbauer L. C. New insights into the role of glycosaminoglycans in the endosteal bone microenvironment. Biol Chem. 2021;402(11):1415-1425. https://doi.org/:10.1515/hsz-2021-0174
18. Menezes R., Vincent R., Osorno L., Hu P., Arinzeh T. L. Biomaterials and tissue engineering approaches using glycosaminoglycans for tissue repair: Lessons learned from the native extracellular matrix. Acta Biomater. 2023;163:210-227. https://doi.org/:10.1016/j.actbio.2022.09.064
19. Li B., Li C., Yan Z., Yang X., Xiao W., Zhang D. et al. A review of self-healing hydrogels for bone repair and regeneration: Materials, mechanisms, and applications. Int J Biol Macromol. 2025;287:138323. https://doi.org/:10.1016/j.ijbiomac.2024.138323
20. Yang Y., Xu L., Wang J., Meng Q., Zhong S., Gao Y. et al. Recent advances in polysaccharide-based self-healing hydrogels for biomedical applications. Carbohydr Polym. 2022;283:119161. https://doi.org/:10.1016/j.carbpol.2022.119161
21. Mehreen A., Faisal M., Zulfiqar B., Hays D., Dhananjaya K., Yaseen F. et al. Connecting Bone Remodeling and Regeneration: Unraveling Hormones and Signaling Pathways. Biology (Basel). 2025;14(3):274. https://doi.org/:10.3390/biology14030274
22. Guo K., Li G., Yu Q., Yang Y., Liu H., Zhao Y. et al. Injectable hyaluronate-based hydrogel with a dynamic/covalent dual-crosslinked architecture for bone tissue engineering: Enhancing osteogenesis and immune regulation. Int J Biol Macromol. 2024;282(Pt 5):137249. https://doi.org/:10.1016/j.ijbiomac.2024.137249
23. Cai B., Fang J., Zhou S., Xie M., Zhang K., Li J. et al. Enzyme-crosslinked hyaluronic acid hydrogel scaffolds for BMSCs microenvironment and wound healing. Int J Biol Macromol. 2025;295:139566. https://doi.org/:10.1016/j.ijbiomac.2025.139566
24. Zhang Y., Xie Y., Hao Z., Zhou P., Wang P., Fang S. et al. Umbilical mesenchymal stem cell-derived exosome-encapsulated hydrogels accelerate bone repair by enhancing angiogenesis. ACS Appl. Mater. Interfaces. 2021;13(16):18472–18487. https://doi.org/:10.1021/acsami.0c22671
25. Xu C., Li Z., Kang M., Chen Y., Sheng R., Aghaloo T. et al. Hydrogel-integrated exosome mimetics derived from osteogenically induced mesenchymal stem cells in spheroid culture enhance bone regeneration. Biomaterials. 2025;317:123088. https://doi.org/:10.1016/j.biomaterials.2025.123088
26. Zhang Y., Fang M., Zhu J., Li T., Li N., Su B. et al. Exosome-loaded hyaluronic acid hydrogel composite with oxygen-producing 3D printed polylactic acid scaffolds for bone tissue repair and regeneration. Int J Biol Macromol. 2024;274(Pt1):132970. https://doi.org/:10.1016/j.ijbiomac.2024.132970
27. Wang Y., Feng Z., Liu X., Yang C., Gao R., Liu W. et al. Titanium alloy composited with dual-cytokine releasing polysaccharide hydrogel to enhance osseointegration via osteogenic and macrophage polarization signaling pathways. Regenerat Biomat. 2022;9:rbac003. https://doi.org/:10.1093/rb/rbac003
28. Yin W., Chen X., Bai L., Li Y., Chen W., Jiang Y. et al. BBPs-functionalized tetrahedral framework nucleic acid hydrogel scaffold captures endogenous BMP-2 to promote bone regeneration. Biomaterials. 2025;319:123194. https://doi.org/:10.1016/j.biomaterials.2025.123194
29. Wang J., Liu M., Yang C., Huang X., Lin C., Zhu Y. et al. Photocrosslinked gelatin methacryloyl/hyaluronic acid methacryloyl composite hydrogels loaded with bone morphogenetic protein 2-black phosphorus nanosheets for bone regeneration. J Biomater Sci Polym Ed. 2025:1-23. https://doi.org/:10.1080/09205063.2025.2489846
30. Choi S., Lee J.S, Shin J., Lee M.S., Kang D., Hwang N.S. et al. Osteoconductive hybrid hyaluronic acid hydrogel patch for effective bone formation. J Contr Release. 2020;327:571–583: https://doi.org/:10.1016/ j.jconrel.2020.09.006
31. Van der Heide D., Hatt L.P., Della Bella E., Hangartner A., Lackington W.A., Yuan H. et al. Characterization and biological evaluation of 3D printed composite ink consisting of collagen, hyaluronic acid and calcium phosphate for bone regeneration. Carbohydr Polym Technol Appl. 2024;7:100518. https://doi.org/:10.1016/j.carpta.2024.100518
32. Hsia T., Lin Z., Xia Y., Shu R., Xie Y. A photoresponsive recombinant human amelogenin-loaded hyaluronic acid hydrogel promotes bone regeneration. J Periodontal Res. 2024;59(3):589–598. https://doi.org/:10.1111/jre.13235
33. Yu L., Wang W., Lv C., Chen Q., Yang P., Qi Z. et al. Dual functional hydrogel of osteoclastic-inhibition and osteogenic-stimulation for osteoporotic bone defect regeneration. Mater Today Bio. 2025;31:101550. https://doi.org/:10.1016/j.mtbio.2025.101550
34. Guo J., Zhang T., Li M., Wang Q., Ding X. Synergistic interactions between physical exercise intervention, innovative materials, and neurovascular coupling in bone repair and injury recovery: a comprehensive review. Biomed Mater. 2025;20(3):032002. https://doi.org/:10.1088/1748-605X/adc5c0
35. Zhang L., Fan J., Ding L., Zhang P., Ye J., Lu T. Enhanced bone regeneration via surface functionalization of biphasic calcium phosphate scaffolds with dopamine-modified hyaluronic acid hydrogel or mg-doped calcium silicate. Int J Biol Macromol. 2025;308(Pt 2):142561. https://doi.org/:10.1016/j.ijbiomac.2025.142561
36. Xu C., Li W., Mao J., Liu Z., Lao A., Mao L. et al. Using chondroitin sulfate lithium hydrogel for diabetic bone regeneration via regulation of macrophage polarization. Carbohydr Polym. 2025;347:122787. https://doi.org/:10.1016/j.carbpol.2024.122787
37. Ao Q., Wang S., He Q., Ten H., Oyama K., Ito A. et al. Fibrin glue/fibronectin/heparin-based delivery system of BMP2 induces osteogenesis in MC3T3-E1 cells and bone formation in rat calvarial critical-sized defects. ACS Appl Mater Interfaces. 2020;12(11):13400-13410. https://doi.org/:10.1021/acsami.0c01371
38. Shettigar R.S., Swathika R., Shetty A., Amrath Rai B. K., Mathew Aranjani J., Mutalik S., et al. Chitosan-based injectable nanocomposite hydrogels for bone tissue regeneration and bone tissue engineering. Intern J Polym Mater Polym Biomater. 2025;1-24. https://doi.org/:10.1080/00914037.2025.2493910
39. Wang S., Lei H., Mi Y., Ma P., Fan D. Chitosan and hyaluronic acid based injectable dual network hydrogels – Mediating antimicrobial and inflammatory modulation to promote healing of infected bone defects. Int J Biol Macromol. 2024;274(Pt 1):133124. https://doi.org/:10.1016/j.ijbiomac.2024.133124
40. Zhou T., Wang F., Liu K., Zhou H., Shang J. An injectable carboxymethyl chitosan-based hydrogel with controlled release of BMP-2 for efficient treatment of bone defects. Int J Biol Macromol. 2024;282(Pt 5):137120. https://doi.org/:10.1016/j.ijbiomac.2024.137120
41. Wang Z., Chu Y., Du J., Hu Y., Wang H., Liu H. et al. Accelerating repair of infected bone defects through post-reinforced injectable hydrogel mediated antibacterial/immunoregulatory microenvironment at bone-hydrogel interface. Carbohydr Polym. 2025;351:123082. https://doi.org/:10.1016/j.carbpol.2024.123082.
42. Sun B., Wang H., Xiao B., Yan H., Wu H., Zhang R. et al. Bioactive composite hydrogel with effects of robust promoting osteogenesis and immunomodulation for osteoporotic bone regeneration. Chem Engineer J. 2023;476:146743. https://doi.org/:10.1016/j.cej.2023.146743
43. Jiang M., Pan Y., Liu Y., Dai K., Zhang Q., Wang J. Effect of sulfated chitosan hydrogel on vascularization and osteogenesis. Carbohydr Polym. 2022;281:119059. https://doi.org/:10.1016/j.carbpol.2021.119059
44. Chen J., Guan X., Chen L., Zheng B., Li F., Fang C. et al. Customized Hydrogel System for the Spatiotemporal Sequential Treatment of Periodontitis Propelled by ZEB1. Adv Sci (Weinh). 2025:2503338. https://doi.org/:10.1002/advs.202503338
45. Xu H., Luo H., Chen J., Chen G., Yu X., Ye Z. BMP-2 releasing mineral-coated microparticle-integrated hydrogel system for enhanced bone regeneration. Front Bioeng Biotechnol. 2023;11:1217335.https://doi.org/: 10.3389/fbioe.2023.1217335
46. Zhang B., Zhou J., Li Y., Chen J., Zhang Y. Bioactive modification of cyclic olefin copolymer (COC) film surfaces by hyaluronic acid and chitosan for enhanced cell adhesion. Int J Biol Macromol. 2024;281(PtI):136169. https://doi.org/:10.1016/j.ijbiomac.2024.136169
47. Wan L., Liu F., Wang A., He Y., Pan J., Liu Y. et al. PI3K/Akt pathway-mediated enhancement of bone and vascular regeneration by gelatin/hyaluronic acid/exosome composite scaffold in bone tissue engineering. Biomater Adv. 2025;166:214064. https://doi.org/:10.1016/j.bioadv.2024.214064
48. Behere I., Vaidya A., Ingavle G. Chondroitin Sulfate and Hyaluronic Acid-Based PolyHIPE Scaffolds for Improved Osteogenesis and Chondrogenesis In Vitro. ACS Appl Bio Mater. 2024;7(8):5222–5236. https://doi.org/:10.1021/acsabm.4c00393
49. Zhang Y., Zhou X., Liu Q., Shen M., Liu Y., Zhang X. Simultaneous co-assembly of collagen and glycosaminoglycans to build a biomimetic extracellular matrix for bone regeneration. Int J Biol Macromol. 2024;279(Pt 3):135535. https://doi.org/:10.1016/j.ijbiomac.2024.135535
50. Rachmiel D., Anconina I., Rudnick-Glick S., Halperin-Sternfeld M., Adler-Abramovich L., Sitt A. Hyaluronic acid and a short peptide improve the performance of a PCL electrospun fibrous scaffold designed for bone tissue engineering applications. Int J Mol Sciences. 2021;22(5):2425. https://doi.org/:10.3390/ijms22052425
51. Gong C., Yang J., Zhang X., Wei Z., Wang X., Huang X. et al. Functionalized Magnesium Phosphate Cement Induces In Situ Vascularized Bone Regeneration via Surface Lyophilization of Chondroitin Sulfate. Biomedicines. 2023;12(1):74. https://doi.org/:10.3390/biomedicines12010074
52. Li M., Liu J., Li Y., Chen W., Yang Z., Zou Y. et al. Enhanced osteogenesis and antibacterial activity of dual-functional PEEK implants via biomimetic polydopamine modification with chondroitin sulfate and levofloxacin. J Biomater Sci Polym Ed. 2024;35(18):2790-2806. https://doi.org/:10.1080/09205063.2024.2390745
53. Xu Z., Chen S., Feng D., Liu Y., Wang Q., Gao T. et al. Biological role of heparan sulfate in osteogenesis: A review. Carbohydr Polym. 2021 Nov 15;272:118490. https://doi.org/:10.1016/j.carbpol.2021.118490
54. Shaffer K.J., Smith R.A., Daines A.M., Luo X., Lu X., Tan T.C. et al. Rational synthesis of a heparan sulfate saccharide that promotes the activity of BMP2. Carbohydr Polym. 2024;333:121979. https://doi.org/:10.1016/j.carbpol.2024.121979.
55. Rahimi M., Mir S. M., Baghban R., Charmi G., Plummer C. M., Shafiei-Irannejad V.et al. Chitosan-based biomaterials for the treatment of bone disorders. Int J Biol Macromol. 2022;215:346–367. https://doi.org/:10.1016/j.ijbiomac.2022.06.079
56. Kudiyarasu S., Karuppan Perumal M.K., Rajan Renuka R., Manickam Natrajan P. Chitosan composite with mesenchymal stem cells: Properties, mechanism, and its application in bone regeneration. Int J Biol Macromol. 2024;275(Pt 1):133502. https://doi.org/:10.1016/j.ijbiomac.2024.133502
57. Li Y., Li X., Zhu L., Liu T., Huang L. Chitosan-based biomaterials for bone tissue engineering. Int J Biol Macromol. 2025;304(Pt 2):140923. https://doi.org/:10.1016/j.ijbiomac.2025.140923.
58. Gutiérrez-Sánchez M., Flores-Rocha S., Pozos-Guillén A., Flores H., Escobar-Barrios V., Palestino-Escobedo A.G. et al. Design, characterization, and biocompatibility of chitosan-nano-hydroxyapatite/tricalcium phosphate sponges. Tissue Cell. 2025;94:102804. https://doi.org/:10.1016/j.tice.2025.102804
59. Danagody B., Bose N., Sudhakar S., Selvaraj V., Rajappan K. Emerita Analoga Shell-Derived CS/GO Composite Incorporated into a Biomimetic PAN Nanofiber Membrane for Enhanced Bone Tissue Regeneration. ACS Appl Bio Mater. 2025;8(4):3239–3253. https://doi.org/: 10.1021/acsabm.4c01963
60. Li M., Jia W., Zhang X., Weng H., Gu G., Chen Z. Hyaluronic acid oligosaccharides modified mineralized collagen and chitosan with enhanced osteoinductive properties for bone tissue engineering. Carbohydr Polym. 2021;260:117780. https://doi.org/:10.1016/j.carbpol.2021.117780
61. Patil B. D., Chamate K. P., Bhosale N. V., Desai N. V., Kadam P. V., Sanap A. et al. A Comprehensive Exploration of Polymeric 3D Sponges for Regeneration of Bone. Regener Engineer Translat Med. 2025;1–34. https://doi.org/:10.1007/s40883-024-00377-7
62. Paraš S., Petrović B., Mitić D., Lazarević M., Popović Bajić M., Živković M. et al. Three-Dimensional-Printed Bone Grafts for Simultaneous Bone and Cartilage Regeneration: A Promising Approach to Osteochondral Tissue Engineering. Pharmaceutics. 2025;17(4):489. https://doi.org/:10.3390/pharmaceutics17040489
63. Yuan L., Zhong S., Ahmad S., Tian D., Ao C. How to select agroforestry waste biomass for electrospinning and its potential application in bone tissue engineering. Carbohydr Polym. 2025;348(PtB):122921. https://doi.org/:10.1016/j.carbpol.2024.122921
64. Lungu A., Dobrișan M. R., Cernencu A. I., Iovu H., Stancu I. C., Olăreț E. et al. GelMA–pectin–polyhedral silsesquioxane nanocomposites for 3D bioprinting of osteogenesis-stimulating scaffolds loaded with BMP-2. Int J Bioprint, 2025;6571. https://doi.org/:10.36922/ijb.6571
65. Li B., Gao Y., Luo X., Hu C., Deng M., Chen J. et al. Cellulose-mediated mechanical property tuning in small intestinal submucosal matrix to enhance stem cell osteogenic differentiation. Int J Biol Macromol. 2025;295:139575. https://doi.org/:10.1016/j.ijbiomac.2025.139575
66. Sreedharan M., Vijayamma R., Liyaskina E., Revin V. V., Ullah M. W., Shi Z. et al. Nanocellulose-based hybrid scaffolds for skin and bone tissue engineering: a 10-year overview. Biomacromolecules. 2024;25(4):2136–2155. https://doi.org/:10.1021/asc.biomac.3c00975
67. Mv S., Parcha S.R. In vitro study of dimethyl glutamate incorporated chitosan/microfibrillated cellulose based matrix in addition of H and Zr on osteoblast cells. Int J Biol Macromol. 2025;289:138889. https://doi.org/:10.1016/j.ijbiomac.2024.138889
68. Yang J., Han Y., Zhang L., Ding Q., Sun S., Zhang S. et al. Taxifolin-loaded cellulose/l-arginine-chitosan hydrogel promoting bone defect repair through osteogenesis and angiogenesis. Int J Biol Macromol. 2024;283(Pt3):137843. https://doi.org/:10.1016/j.ijbiomac.2024.137843
69. Yang M., Cai X., Wang C., Li P., Chen S., Liu C. et al. Humidity-Responsive Amorphous Calcium–Magnesium Pyrophosphate/Cassava Starch Scaffold for Enhanced Neurovascular Bone Regeneration. ACS Appl Mater Interfaces. 2024;16(28):35964–35984. https://doi.org/:10.1021/acsami.4c03204
70. Chen X., Xu C., Geng T., Geng Y., Li Z., Li Y. et al. Injectable Self-Healing Oxidized Starch/Gelatin Hybrid Hydrogel for Preventing Aseptic Loosening of Bone Tissue Engineering. ACS Appl Mater Interfaces, 2024;16(5):5368–5381. https://doi.org/:10.1021/acsami.3c12605
71. Machado A., Pereira I., Pereira J. E., Maltez L., Brandão A., Alvites R. et al. Dextrin hydrogel loaded with a macroporous Bonelike® scaffold and dental pulp stem cells for critical-sized defect repair. Materialia, 2023;30:101859. https://doi.org/:10.1016/j.mtla.2023.101859
72. Zhang Y., Fang M., Yu L., Liu X., Wang J., Li N. et al. Enhanced cellular viability and osteogenic activity in oxygen-self-generating and magnetically responsive alginate microgels as advanced cell carriers. Biomater Adv. 2025;170:214198. https://doi.org/:10.1016/j.bioadv.2025.214198
73. Quan H., Ren C., Xie H., He Z., Ding H., Li J. et al. An injectable hydrogel loaded with miRNA nanocarriers promotes vessel-associated osteoclast (VAO)-mediated angiogenesis and bone regeneration in osteonecrosis of the rat femoral head. Biomaterials. 2025;320:123252. https://doi.org/:10.1016/j.biomaterials.2025.123252
74. Liying Q., Yining Y., Yongjian S., Guojiang H., Wenli D., Baoqin H. et al. Incorporation of carboxymethyl chitosan (CMCS) for the modulation of physio-chemical characteristics and cell proliferation environment of the composite hydrogel microspheres. Biomed Mater. 2024;19(6). https://doi.org/:10.1088/1748-605X/ad7565
75. Li Y., Liu J., Wei J., Yuan L., Hu J., Dai S. et al. Porous Hydrogels Prepared by Two-Step Gelation Method for Bone Regeneration. J Funct Biomater. 2025;16(3):100. https://doi.org/:10.3390/jfb16030100
76. Lee S., Park H., Yun H.S., Kang B.J. Alginate Beads Encapsulating Hydroxyapatite Microparticle and BMP-2 for Long Bone Defect Regeneration: A Pilot Study. In Vivo. 2025;39(2):732-741. https://doi.org/:10.21873/invivo.13877
77. Wu T., Liu L., Gao Z., Cui C., Fan C., Liu Y. et al. Extracellular matrix (ECM)-inspired high-strength gelatin-alginate based hydrogels for bone repair. Biomater Sci. 2023;11(8):2877–2885. https://doi.org/:10.1039/d3bm00213f
78. Park B., Yu S.N., Kim S.H., Lee J., Choi S.J., Chang J.H. et al. Inhibitory Effect of Biotransformed-Fucoidan on the Differentiation of Osteoclasts Induced by Receptor for Activation of Nuclear Factor-κB Ligand. J Microbiol Biotechnol. 2022;32(8):1017–1025. https://doi.org/:10.4014/jmb.2203.03001
79. Amupama D.V.K., Udduttula A., Jaiswal A.K. Unveiling the secrets of marine-derived fucoidan for bone tissue engineering-A review. Front Bioeng Biotechnol. 2023;10:1100164. https://doi.org/:10.3389/fbioe.2022.1100164
80. Dadashi Ouranj Z., Hosseini S., Alipour A., Homaeigohar S., Azari S., Ghazizadeh L. et al. The potent osteo-inductive capacity of bioinspired brown seaweed-derived carbohydrate nanofibrous three-dimensional scaffolds. Mar Life Science Technol. 2024;6(3):515-534. https://doi.org/:10.1007/s42995-024-00241-1
81. Kwack K.H., Ji J.Y., Park B., Heo J.S. Fucoidan (Undaria pinnatifida)/Polydopamine Composite-Modified Surface Promotes Osteogenic Potential of Periodontal Ligament Stem Cells. Mar Drugs. 2022;20(3):181. https://doi.org/:10.3390/md20030181
82. Lu H.T., Huang G.Y., Chang W.J., Lu T.W., Huang T.W., Ho M.H. et al. Modification of chitosan nanofibers with CuS and fucoidan for antibacterial and bone tissue engineering applications. Carbohydr Polym. 2022;281:119035. https://doi.org/:10.1016/j.carbpol.2021.119035
83. Udayakumar S., Girigoswami A., Girigoswami K. Biological activities of carrageenan from red algae: a mini review. Curr Pharmacol Reports, 2024;10(1):12–26. https://doi.org/:10.1007/s40495-023-00348-6
84. Zhang H., Ding S., Xue H., Wang S, Quan X., Zhang D. et al. Injectable organic-inorganic hybrid hydrogels for bone defect repair. Front Bioeng Biotechnol. 2025;13:1563546. https://doi.org/:10.3389/fbioe.2025.1563546
85. Haroon B., Sohail M., Minhas M.U., Mahmood A., Hussain Z., Ahmed Shah S. et al. Nano-residronate loaded κ-carrageenan-based injectable hydrogels for bone tissue regeneration. Int J Biol Macromol. 2023;251:126380. https://doi.org/:10.1016/j.ijbiomac.2023.126380
86. Kikionis S., Iliou K., Karra A.G., Polychronis G., Choinopoulos I., Iatrou H. et al. Development of Bi- and Tri-Layer Nanofibrous Membranes Based on the Sulfated Polysaccharide Carrageenan for Periodontal Tissue Regeneration. Mar Drugs. 2023;21(11):565. https://doi.org/:10.3390/md21110565.
87. Sudhakar M. P., Ali S., Chitra S. Scrutinizing the effect of rGO-cuttlefish bone hydroxyapatite composite infused carrageenan membrane towards wound reconstruction. Int J Biol Macromol. 2024;262(Pt2):130155. https://doi.org/:10.1016/j.ijbiomac.2024.130155
88. Vargas-Osorio Z., González Castillo E.I., Mutlu N., Vidomanová E., Michálek M., Galusek D. et al. Tailorable mechanical and degradation properties of KCl-reticulated and BDDE-crosslinked PCL/chitosan/κ-carrageenan electrospun fibers for biomedical applications: Effect of the crosslinking-reticulation synergy. Int J Biol Macromol. 2024;265(Pt1):130647. https://doi.org/:10.1016/j.ijbiomac.2024.130647
89. Bajpai D., Kaarthikeyan G. Development and evaluation of alginate-and carrageenan-incorporated scaffold for bone regeneration: an in vitro study. Cureus, 2024;16(5):e61139. https://doi.org/:10.7759/cureus.61139
90. Loukelis K., Papadogianni D., Chatzinikolaidou M. Kappa-carrageenan/chitosan/gelatin scaffolds enriched with potassium chloride for bone tissue engineering. Int J Biol Macromol. 2022;209(Pt B):1720–1730. https://doi.org/.org/:10.1016/j.ijbiomac.2022.04.129
