Synthesis and properties of hydrogels based on collagen–pectin–methyl methacrylate copolymers synthesized in the presence of triethylborane

Collagen–pectin–methyl methacrylate copolymers were synthesized in an acetic acid dispersion in the presence of a triethylboron amine complex. The synthesis temperature was found to have little effect on the copolymer composition, while its morphology changed significantly. By using the amine complex in combination with p-quinone during the synthesis of collagen–pectin–methyl methacrylate copolymers, it was possible to vary the copolymer composition, the molecular weight of grafted polymethyl methacrylate, and the resulting morphology depending on the structure of the p-quinone used. Hydrogels based on the synthesized copolymers were formed in the presence of glutaric aldehyde. Their moisture-absorbing properties and stability in buffer solutions make them promising base materials for regenerative medicine. The absence of cytotoxicity and the stimulatory effect of the obtained materials on the growth of human dermal fibroblasts were demonstrated by the MTT assay. The analysis of biocidal activity indicates that collagen–pectin–methyl methacrylate hydrogels have a clear potential as fungusresistant bactericidal materials.

1. Liu L., Fan X., Lu Q., Wang P., Wang X., Han Y., Wang R., Zhang C., Han S., Tsuboi T., Dai H., Yeow J., Geng H. Antimicrobial research of carbohydrate polymer- and protein-based hydrogels as reservoirs for the generation of reactive oxygen species: A review. Int. J. Biol. Macromol., 2024, vol. 260, pt. 1, art. 129251. https://doi.org/10.1016/j.ijbiomac.2024.129251.

2. Zhang R., Liu X., Zhang W., Cui B., Du Y., Huang Y., Li W., Liu Q., Ren C., Tang Z. A review of polysaccharide-based hydrogels: From structural modification to biomedical applications. Int. J. Biol. Macromol., 2025, vol. 310, pt. 4, art. 143519. https://doi.org/10.1016/j.ijbiomac.2025.143519.

3. Guo Y., Zhao C., Yan C, Cui L. Construction of cellulose/carboxymethyl chitosan hydrogels for potential wound dressing application. Cellulose, 2021, vol. 28, no. 15, pp. 10013–10023. https://doi.org/10.1007/s10570-021-04149-2.

4. Huang W., Wang Y., Huang Z., Wang X., Chen L., Zhang Y., Zhang L. On-demand dissolvable self-healing hydrogel based on carboxymethyl chitosan and cellulose nanocrystal for deep partial thickness burn wound healing. ACS Appl. Mater. Interfaces, 2018, vol. 10, no. 48, pp. 41076−41088. https://doi.org/10.1021/acsami.8b14526.

5. Espinales C., Romero-Peña M., Calderón G., Vergara K., Cáceres P.J., Castillo P. Collagen, protein hydrolysates and chitin from by-products of fish and shellfish: An overview. Heliyon, 2023, vol. 9, no. 4, art. e14937. https://doi.org/10.1016/j.heliyon.2023.e14937.

6. Ozogul F., Cagalj M., Šimat V., Ozogul Y., Tkaczewska J., Hassoun A., Kaddour A.A., Kuley E., Rathod N.B., Phadke G.G. Recent developments in valorisation of bioactive ingredients in discard/seafood processing by-products. Trends Food Sci. Technol., 2021, vol. 116, pp. 559–582. https://doi.org/10.1016/j.tifs.2021.08.007.

7. Siddiqui S.A., Rahmadhia S.N., Nair S., Sabu S., Ahmad A., Sasidharan A. Unlocking the extraction potential of bionanomaterials from aquatic sources and byproducts – a comprehensive review. Process Saf. Environ. Prot., 2024, vol. 191, pt. A, pp. 959–982. https://doi.org/10.1016/j.psep.2024.08.035.

8. Wang M., Cheng Y., Li X., Nian L., Yuan B., Cheng S., Wang S., Cao C. Effects of microgels fabricated by microfluidic on the stability, antioxidant, and immunoenhancing activities of aquatic protein. J. Future Foods, 2025, vol. 5, no. 1, pp. 57–67. https://doi.org/10.1016/j.jfutfo.2024.01.005.

9. Mehvari F., Ramezanzade V., An J., Kim J., Dinari M., Kim J.S. Biopolymer-based hydrogels for biomedical applications: Bioactivity and wound healing properties. Coord. Chem. Rev., 2024, vol. 518, art. 216093. https://doi.org/10.1016/j.ccr.2024.216093.

10. Alsalhi A. Applications of selected polysaccharides and proteins in dentistry: A review. Int. J. Biol. Macromol., 2024, vol. 260, pt. 1, art. 129215. https://doi.org/10.1016/j.ijbiomac.2024.129215.

11. Alqahtani N.F. Functionalized imidazolium ionic liquids-modified chitosan materials: From synthesis approaches to applications. React. Funct. Polym., 2024, vol. 194, art. 105779. https://doi.org/10.1016/j.reactfunctpolym.2023.105779.

12. Yang R., Xia C., Mei C., Li J. Integration of biopolymers in polyacrylic acid hydrogels: Innovations and applications in bioresources and bioproducts. J. Bioresour. Bioprod., 2025, vol. 10, no. 2, pp. 145–169. https://doi.org/10.1016/j.jobab.2024.12.005.

13. Hou X., Lin L., Li K., Jiang F., Qiao D., Zhang B., Xie F. Towards superior biopolymer gels by enabling interpenetrating network structures: A review on types, applications, and gelation strategies. Adv. Colloid Interface Sci., 2024, vol. 325, art. 103113. https://doi.org/10.1016/j.cis.2024.103113.

14. Patel D.K., Jung E., Priya S., Won S.-Y., Han S.S. Recent advances in biopolymer-based hydrogels and their potential biomedical applications. Carbohydr. Polym., 2024, vol. 323, art 121408. https://doi.org/10.1016/j.carbpol.2023.121408.

15. Kuznetsova Yu.L., Lobanova K.S., Gushchina K.S., Vedernikova N.V., Rumyantseva V.O., Mitin A.V., Khmelevskiy K.P., Vavilova A.S., Semenycheva L.L. Peculiarities of formation of 3D structures for regenerative medicine based on collagen, pectin, and acrylic monomers in the presence of a triethylboron complex with hexamethylenediamine. Polym. Sci., Ser. D., 2025, vol. 18, no. 1, pp. 190–197. https://doi.org/10.1134/S1995421224702101.

16. Kuznetsova Y.L., Gushchina K.S., Lobanova K.S., Chasova V.O., Egorikhina M.N., Grigoreva A.O., Malysheva Y.B., Kuzmina D.A., Farafontova E.A., Linkova D.D., Rubtsova Y.P., Semenycheva L.L. Scaffold chemical model based on collagen–methyl methacrylate graft copolymers. Polymers, 2023, vol. 15, no. 12, art. 2618. https://doi.org/10.3390/polym15122618.

17. Armarego W.L.F., Chai C.L.L. Purification of Laboratory Chemicals. 7th ed. Waltham, MA, Butterworth-Heinemann, 2013. 1024 p.

18. Semenycheva L.L., Astanina M.V., Kuznetsova Y.L., Valetova N.B., Geras’kina E.V., Tarankova O.A. Method for production of acetic dispersion of high molecular fish collagen. Patent RF no. 2567171. Byull. FIPS, 2015, no. 31. (In Russian)

19. Morozov L.A. Metody analiza akrilatov i metakrilatov [Methods for Analysis of Acrylates and Methacrylates]. Moscow, Khimiya, 1972. 232 p. (In Russian)

20. State Standard R ISO 10993-5:2009. Medical devices. Biological evaluation of medical devices. Part 5: Tests for in vitro cytotoxicity. Moscow, Standartinform, 2010. 10 p. (In Russian)

21. Egorikhina M.N., Kobyakova I.I., Charykova I.N., Linkova D.D., Rubtsova Y.P., Farafontova E.A., Aleynik D.Ya. Application of hydrogel wound dressings in cell therapy-approaches to assessment in vitro. Int. J. Burns Trauma, 2023, vol. 13, no. 2, pp. 13–32.

22. State Standard 9.049-91. Unified system of corrosion and ageing protection. Polymer materials and their components. Methods of laboratory tests for mould resistance. Moscow, Izd. Stand., 1992. 14 p. (In Russian)

23. Kuznetsova Y., Gushchina K., Sustaeva K., Mitin A., Egorikhina M., Chasova V., Semenycheva L. Grafting of methyl methacrylate onto gelatin initialed by tri-butylborane– 2,5-di-tert-butyl-p-benzoquinone system. Polymers, 2022, vol. 14, no. 16, art. 3290. https://doi.org/10.3390/polym14163290.

24. Kuznetsova Yu.L., Gushchina K.S., Lobanova K.S., Rumyantseva V.O., Egorikhina M.N., Farafontova E.A., Rubtsova Yu.P., Semenycheva L.L. Synthesis of grafted copolymers of cod collagen and acrylamides in the presence of alkylborane – p-quinone system. Proc. Univ. Appl. Chem. Biotechnol., 2024, vol. 14, no. 3, pp. 305–321. https://doi.org/10.21285/achb.938. (In Russian)

25. Köster R., Amen K.-L., Dahlhoff W.V. Borverbindungen, XXX. O-Dialkylborylierungen von sacchariden und polyolen. Justus Liebigs Ann. Chem., 1975, Bd. 1975, H. 4, S. 752–788. https://doi.org/10.1002/jlac.197519750417.

26. Allies P.G., Brindley P.B. Mechanism of autoxidation of trialkylboranes. J. Chem. Soc., B, 1969, pp. 1126–1131. https://doi.org/10.1039/J29690001126.

27. Liu S., Zheng Z., Li M., Wang X. Effect of oxidation progress of tributylborane on the grafting of polyolefins. J. Appl. Polym. Sci., 2012, vol. 125, no. 5, pp. 3335–3344. https://doi.org/10.1002/app.34232.

28. Zaremskii M.Yu., Odintsova V.V., Plutalova A.V., Gurskii M.E., Bubnov Yu.N. Reactions of initiation and reinitiation in polymerization mediated by organoborane–oxygen systems. Polym. Sci., Ser. B, 2018, vol. 60, no. 2, pp. 162–171. https://doi.org/10.1134/S1560090418020082.

29. Dodonov V.A., Kuznetsova Yu.L., Vilkova A.I., Skuchilina A.S., Nevodchikov V.I., Beloded L.N. Uncontrolled pseudoliving free-radical polymerization of methyl methacrylate in the presence of butyl-p-benzoquinones // Russ. Chem. Bull., 2007, vol. 56, no. 6, pp. 1162–1165. https://doi.org/10.1007/s11172-007-0176-z.

30. Dodonov V.A., Kuznetsova Yu.L., Lopatin M.A., Skatova A.A. Reactions of poly(methyl methacrylate) radicals with some p-quinones in the presence of tri-n-butylboron in methyl methacrylate polymerization. Russ. Chem. Bull., 2004, vol. 53, no. 10, pp. 2209–2214. https://doi.org/10.1007/s11172-005-0101-2.

31. Kuznetsova Yu.L., Chesnokov S.A., Zaitsev S.D., Dodonov V.A. Photopolymerization of methyl methacrylate in the presence of the tri-n-butyl boron–p-quinone system. Polym. Sci., Ser. B, 2010, vol. 52, nos. 3–4, pp. 129–135. https://doi.org/10.1134/S1560090410030024.

32. Pegoretti A., Dong Y., Slouf M. Biodegradable matrices and composites. Front. Mater., 2020, vol. 7, art. 265. https://doi.org/10.3389/fmats.2020.00265.

33. Perez-Puyana V., Jiménez-Rosado M., Romero A., Guerrero A. Crosslinking of hybrid scaffolds produced from collagen and chitosan. Int. J. Biol. Macromol., 2019, vol. 139, pp. 262–269. https://doi.org/10.1016/j.ijbiomac.2019.07.198.

34. Murav’ev I.A. Biofarmatsevticheskie osnovy tekhnologii lekarstv i ikh ispol’zovanie v deyatel’nosti aptechnykh uchrezhdenii GAPU MZ SSSR [Biopharmaceutical Principles of Drug Technology and Their Use in the Work of Pharmacy Institutions of the Chief Pharmacy Directorate of the Ministry of Health of the USSR]. Pyatigorsk, PFI, 1983. 42 p. (In Russian)