Characteristics of interpenetrating hydrogels based on fibrin and high molecular weight polyvinyl alcohol

Aim. In an in vitro experiment, to study the properties of the IPN hydrogel fibrin/high-molecular polyvinyl alcohol with an increased number of cryocycles and fibrinogen concentrations to assess the prospects for its use in the creation of small-diameter vascular prostheses.

Materials and Methods. One-component samples of fibrin hydrogels containing 40 and 50 mg/ ml fibrinogen, PVA polymer (146000-186000 Da) 30 and 40 mg/ml and the corresponding groups of IPN hydrogel samples were polymerized: fibrin 40 mg/ml and PVA 30 mg/ml (F40P30), fibrin 40 mg/ ml and PVA 40 mg/ml (F40P40), fibrin 50 mg/ml and PVA 30 mg/ml (F50P30), fibrin 50 mg/ml and PVA 40 mg/ml (F50P40). PVA was cryostructured for 5 cycles.

The structural properties of the samples were studied using SEM, histological staining of sections with hematoxylin and eosin, and IR spectroscopy. Biological properties were assessed by the viability, number and metabolic activity of cells colonized on the materials. The physical and mechanical properties of the samples were characterized by tensile strength, relative elongation and Young's modulus. The hemocompatibility of materials was assessed by contact activation of platelets and the percentage of erythrocyte hemolysis.

Results. Sequential polymerization of fibrin and high-molecular-weight PVA produced an IPN hydrogel with a uniform distribution of components in the thickness and lower surface, but a predominant presence of PVA on the upper surface. The structural heterogeneity of the material affected the biological properties. The lower surface of IPN hydrogels showed higher biocompatibility compared to the upper surface.

The strength of IPN hydrogels increased with increasing PVA molecular weight, concentration and number of cryocycles, but did not reach a. mammaria. Hydrogels do not hemolyze red blood cells and do not activate platelets.

Conclusion. Using a technique of sequential polymerization of fibrin and high molecular weight PVA over five cryocycles, a double-sided IPN hydrogel with high biocompatibility on the lower side and improved strength was obtained. However, the physical and mechanical characteristics of IPN hydrogel were weaker than a. mammaria, which requires new solutions.

1. Suamte L, Tirkey A, Barman J, Jayasekhar Babu P. Various manufacturing methods and ideal properties of scaffolds for tissue engineering applications. Smart Materials in Manufacturing. 2023;1:100011. https://doi.org/10.1016/j.smmf.2022.100011

2. Crosby CO, Stern B, Kalkunte N, Pedahzur S, Ramesh S, Zoldan J. Interpenetrating polymer network hydrogels as bioactive scaffolds for tissue engineering. Rev Chem Eng. 2022;38(3):347-361. https://doi.org/10.1515/revce-2020-0039

3. Valdoz JC, Johnson BC, Jacobs DJ, Franks NA, Dodson EL, Sanders C, Cribbset CG, Ryal PV. The ECM: To Scaffold, or Not to Scaffold, That Is the Question. Int J Mol Sci. 2021;22(23):12690. https://doi.org/10.3390/ijms222312690

4. Matveeva VG, Khanova MU, Antonova LV, Barbarash LS. Fibrin – a promising material for vascular tissue engineering. Russian Journal of Transplantology and Artificial Organs. 2020;22(1):196-208. (In Russian). https://doi.org/10.15825/1995-1191-2020-1-196-208

5. Park CH, Woo KM. Fibrin-Based Biomaterial Applications in Tissue Engineering and Regenerative Medicine. Adv Exp Med Biol. 2018;1064:253-261. https://doi.org/10.1007/978-981-13-0445-3_16

6. Bidault L, Deneufchatel M, Vancaeyzeele C, Fichet O, Larreta-Garde V. Self-supported fibrin-polyvinyl alcohol interpenetrating polymer networks: an easily handled and rehydratable biomaterial. Biomacromolecules. 2013;14(11):3870-3879. https://doi.org/10.1021/bm400991k. https://pubmed.ncbi.nlm.nih.gov/24050436/

7. Bidault L, Deneufchatel M, Hindié M, Vancaeyzeele C, Fichet O, Larreta-Garde V. Fibrin-based interpenetrating polymer network biomaterials with tunable biodegradability. Polymer. 2015;62:19-27. https://doi.org/10.1016/j.polymer.2015.02.014

8. Matveeva VG, Rezvova MA, Glushkova TV, Sergeeva AV, Krivkina EO, Antonova LV, Barbarash LS. Structure and properties of a hydrogel with an interpenetrating polymer network fibrin/polyvinyl alcohol as a modifying coating for small-caliber vessel prostheses. Circulatory pathology and cardiac surgery. 2023;27(2):74-86. (In Russian). https://doi.org/10.21688/1681-3472-2023-2-74-86

9. Antonova LV, Matveeva VG, Khanova MYu, Barbarash OL, Barbarash LS. Method for the manufacture of autologous fibrin with controlled fibrinogen content without the use of exogenous thrombin. Patent RU №2758260 C1. 27.10.2021 (In Russian). Available at: https://elibrary.ru/download/elibrary_47122803_25649697.PDF. Accessed: 04.11.2024.

10. Blat A, Dybas J, Chrabaszcz K, Bulat K, Jasztal A, Kaczmarska M, Pulyk R, Popiela T, Slowik A, Malek K, Adamski MG, Marzec KM. FTIR, Raman and AFM characterization of the clinically valid biochemical parameters of the thrombi in acute ischemic stroke. Sci Rep. 2019;9:15475. https://doi.org/10.1038/s41598-019-51932-0

11. Sa’adon S, Ansari MNM, Razak SIA, Anand JS, Nayan NHM, Ismail AE, Khan MUA, Haider A. Preparation and Physicochemical Characterization of a Diclofenac Sodium-Dual Layer Polyvinyl Alcohol Patch. Polymers. 2021;13:2459. https://doi.org/10.3390/polym13152459

12. Choo K, Ching YC, Chuah CH, Julai S, Liou NS. Preparation and Characterization of Polyvinyl Alcohol-Chitosan Composite Films Reinforced with Cellulose Nanofiber. Materials (Basel). 2016;9(8):644. https://doi.org/10.3390/ma9080644

13. Dattola E, Parrotta EI, Scalise S, Perozziello G, Limongi T, Candeloro P, Coluccio ML, Maletta C, Bruno L, De Angelis MT, Santamaria G, Mollace V, Lamanna E, Fabrizio EDi, Cuda G. Development of 3D PVA scaffolds for cardiac tissue engineering and cell screening applications. RSC Adv. 2019;9(8):4246-4257. https://doi.org/10.1039/c8ra08187e

14. Sanz-Horta R, Matesanz A, Gallardo A, Reinecke H, Jorcano JL, Acedo P, Velasco D, Elvira C. Technological advances in fibrin for tissue engineering. J Tissue Eng. 2023;14:20417314231190288. https://doi.org/10.1177/20417314231190288

15. Jin SG. Production and application of biomaterials based on polyvinyl alcohol (PVA) as wound dressing. Chem Asian J. 2022;17:e202200595. https://doi.org/10.1002/asia.202200595

16. Mariani E, Lisignoli G, Borzì RM, Pulsatelli L. Biomaterials: Foreign bodies or tuners for the immune response? Int J Mol Sci. 2019;20(3):636. https://doi.org/10.3390/ijms20030636

17. Micol LA, Ananta M, Engelhardt EM, Mudera VC, Brown RA, Hubbell JA, Frey P. High-density collagen gel tubes as a matrix for primary human bladder smooth muscle cells. Biomaterials. 2011;32(6):1543- 1548. https://doi.org/10.1016/j.biomaterials.2010.10.028

18. Levina EM, Kharitonova MA, Rovensky YA, Vasiliev JM. Cytoskeletal control of fibroblast length: experiments with linear strips of substrate. J Cell Sci. 2001;114(Pt 23):4335-4341. https://doi.org/10.1242/jcs.114.23.4335.