The growing number of female reproductive system disorders creates a need for novel treatment methods. Tissue engineering brings hope for patients, which enables damaged tissue reconstruction. For this purpose, epithelial cells are cultured on three-dimensional scaffolds. One of the most promising materials is chitosan, which is known for its biocompatibility and biodegradability. The aim of the following study was to verify the potential of chitosan-based biomaterials for pelvic organ prolapse regeneration. The scaffolds were obtained under microwave-assisted conditions in crosslinking reactions, using dicarboxylic acids and aminoacid as crosslinkers, including l-glutamic acid, adipic acid, malonic acid, and levulinic acid. The products were characterized over their physicochemical and biological properties. FT-IR analysis confirmed formation of amide bonds. The scaffolds had a highly porous structure, which was confirmed by SEM analysis. Their porosity was above 90%. The biomaterials had excellent swelling abilities and very good antioxidant properties. The cytotoxicity study was performed on vaginal epithelial VK2/E6E7 and human colon cancer HCT116 cell lines. The results showed that after certain modifications, the proposed scaffolds could be used in pelvic organ prolapse (POP) treatment.

Department of Biotechnology and Physical Chemistry Faculty of Chemical Engineering and Technology Cracow University of Technology Warszawska 24 Street 31 155 Cracow Poland

Faculty of Mining and Geology Technical University of Ostrava 708 00 Ostrava Czech Republic

Gynecology and Oncology Department Jagiellonian University Collegium Medicum Kopernika 23 31 501 Kraków Poland

Transplantology Department Jagiellonian University Collegium Medicum Wielicka 265 30 663 Kraków Poland

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Stangel-Wójcikiewicz K., Jarocha D., Piwowar M., Jach R., Uhl T., Basta A., Majka M. Autologous muscle-derived cells for the treatment of female stress urinary incontinence: A 2-year follow-up of a Polish investigation. Neurourol. Urodyn. 2014;33:324–330. doi: 10.1002/nau.22404. PubMed DOI

Wu J.M., Vaughan C.P., Goode P.S., Redden D.T., Burgio K.L., Richter H.E., Markland A.D. Prevalence and trends of symptomatic pelvic floor disorders in US women. Obs. Gynecol. 2014;123:141–148. doi: 10.1097/AOG.0000000000000057. PubMed DOI PMC

Stangel-Wójcikiewicz K., Stec M., Nikolavsky D., Chancellor M.B. Cellular therapy for treatment of stress urinary incontinence. Curr. Stem. Cell. Res. 2010;5:57–62. doi: 10.2174/157488810790442840. PubMed DOI

Stangel-Wójcikiewicz K., Piwowar M., Jach R., Majka M., Basta A. Quality of life assessment in female patients 2 and 4 years after muscle-derived cell transplants for stress urinary incontinence treatment. Ginekol. Pol. 2016;87:183–189. doi: 10.17772/gp/61330. PubMed DOI

Pence J.C., Clancy K.B., Harley B.A. The induction of pro-angiogenic processes within a collagen scaffold via exogenous estradiol and endometrial epithelial cells. Biotechnol. Bioeng. 2015;112:2185–2194. doi: 10.1002/bit.25622. PubMed DOI PMC

Dällenbach P. To mesh or not to mesh: A review of pelvic organ reconstructive surgery. Int. J. Womens Health. 2015;7:331–343. doi: 10.2147/IJWH.S71236. PubMed DOI PMC

Barski D., Deng Y. Management of Mesh Complications after SUI and POP Repair: Review and Analysis of the Current Literature. BioMed Res. Int. 2015;2015:831285. doi: 10.1155/2015/831285. PubMed DOI PMC

Blaivas J.G., Purohit R.S., Benedon M.S., Mekel G., Stern M., Billah M., Bendavid R., Iakovlev V. Safety considerations for synthetic sling surgery. Nat. Rev. Urol. 2015;12:481–509. doi: 10.1038/nrurol.2015.183. PubMed DOI

Mangır N., Hillary C.J., Chapple C.R., MacNeil S. Oestradiol-releasing biodegradable mesh stimulates collagen production and angiogenesis: An approach to improving biomaterial integration in pelvic floor repair. Eur. Urol. Focus. 2019;5:280–289. doi: 10.1016/j.euf.2017.05.004. PubMed DOI

Alperin M. Collagen scaffold: A treatment for large mesh exposure following vaginal prolapse repair. Int. Urogynecol. J. 2014;25:1597–1599. doi: 10.1007/s00192-014-2427-5. PubMed DOI PMC

Mangera A., Bullock A.J., Roman S., Chapple C.R., MacNeil S. Comparison of candidate scaffolds for tissue engineering for stress urinary incontinence and pelvic organ prolapse repair. BJU Int. 2013;112:674–685. doi: 10.1111/bju.12186. PubMed DOI

Roman S., Mangera A., Osman N.I., Bullock A.J., Chapple C.R., MacNeil S. Developing a tissue engineered repair material for treatment of stress urinary incontinence and pelvic organ prolapse-which cell source? Neurourol. Urodyn. 2014;33:531–537. doi: 10.1002/nau.22443. PubMed DOI

Wang X., Chen Y., Fan Z., Hua K. Comparing different tissue-engineered repair materials for the treatment of pelvic organ prolapse and urinary incontinence: Which material is better? Int. Urogynecol. J. 2018;29:131–138. doi: 10.1007/s00192-017-3406-4. PubMed DOI

Shi L.B., Cai H.X., Chen L.K., Wu Y., Zhu S.A., Gong X.N., Xia Y.X., Ouyang H.W., Zou X.H. Tissue engineered bulking agent with adipose-derived stem cells and silk fibroin microspheres for the treatment of intrinsic urethral sphincter deficiency. Biomaterials. 2014;35:1519–1530. doi: 10.1016/j.biomaterials.2013.11.025. PubMed DOI

Grooms T.N., Vuong H.R., Tyo K.M., Malik D.A., Sims L.B., Whittington C.P., Palmer K.E., Matoba N., Steinbach-Rankins J.M. Griffithsin-Modified Electrospun Fibers as a Delivery Scaffold To Prevent HIV Infection. Antimicrob. Agents. Chem. 2016;11:6518–6531. doi: 10.1128/AAC.00956-16. PubMed DOI PMC

Younes I., Rinaudo M. Chitin and Chitosan Preparation from Marine Sources. Structure, Properties and Applications. Mar. Drugs. 2015;13:1133–1174. doi: 10.3390/md13031133. PubMed DOI PMC

Rinaudo M. Chitin and chitosan: Properties and applications. Prog. Polym. Sci. 2006;31:603–632. doi: 10.1016/j.progpolymsci.2006.06.001. DOI

Rong H.C., Hwa H.D. Effect of molecular weight of chitosan with the same degree of deacetylation on the thermal, mechanical, and permeability properties of the prepared membrane. Carbohydr. Polym. 1996;29:353–358. doi: 10.1016/S0144-8617(96)00007-0. DOI

Mima S., Miya M., Iwamoto R., Yoshikawa S. Highly deacetylated chitosan and its properties. J. Appl. Polym. Sci. 1983;28:1909–1917. doi: 10.1002/app.1983.070280607. DOI

Smith J., Wood E., Dornish M. Effect of chitosan on epithelial cell tight junctions. Pharm. Res. 2004;21:43–49. doi: 10.1023/B:PHAM.0000012150.60180.e3. PubMed DOI

Patil S.V., Nanduri L.S.Y. Interaction of chitin/chitosan with salivary and other epithelial cells—An overview. Int. J. Biol. Macromol. 2017;104:1398–1406. doi: 10.1016/j.ijbiomac.2017.03.058. PubMed DOI

Choi J.S., Yoo H.S. Pluronic/chitosan hydrogels containing epidermal growth factor with wound-adhesive and photo-crosslinkable properties. J. Biomed. Mater. Res. A. 2010;95:564–573. doi: 10.1002/jbm.a.32848. PubMed DOI

Wetta L.A., Gerten K.A., Wheeler T.L., Holley R.L., Varner R.E., Richter H.E. Synthetic graft use in vaginal prolapse surgery: Objective and subjective outcomes. Int. Urogynecol. J. 2009;20:1307–1312. doi: 10.1007/s00192-009-0953-3. PubMed DOI PMC

Kaczmarek B., Sionkowska A., Osyczka A.M. Scaffolds based on chitosan and collagen with glycosaminoglycans crosslinked by tannic acid. Polym. Test. 2018;65:163–168. doi: 10.1016/j.polymertesting.2017.11.026. DOI

Kaya M., Baran T., Asan-Ozusaglam M., Cakmak Y.S., Tozak K.O., Mol A., Mentes A., Sezen G. Extraction and characterization of chitin and chitosan with antimicrobial and antioxidant activities from cosmopolitan Orthoptera species (Insecta) Biotechnol. Bioproc. Eng. 2015;20:168–179. doi: 10.1007/s12257-014-0391-z. DOI

Piątkowski M., Janus Ł., Radwan-Pragłowska J., Bogdał D., Matysek D. Biodegradable, pH-sensitive chitosan beads obtained under microwave radiation for advanced cell culture. Colloids Surface B. 2018;164:324–331. doi: 10.1016/j.colsurfb.2018.01.061. PubMed DOI

Radwan-Pragłowska J., Piątkowski M., Janus Ł., Bogdał D., Matysek D. Biodegradable, pH-responsive chitosan aerogels for biomedical applications. RSC Adv. 2017;7:32960–32965. doi: 10.1039/C6RA27474A. DOI

Piątkowski M., Kitala D., Radwan-Pragłowska J., Janus Ł., Klama-Baryła A., Łabuś W., Tomanek E., Glik J., Matýsek D., Kawecki M. Chitosan/aminoacid hydrogels with antimicrobial and bioactive properties as new scaffolds for human mesenchymal stem cells culture applicable in wound healing. Express Polym. Lett. 2018;11:100–112. doi: 10.3144/expresspolymlett.2018.8. DOI

Piątkowski M., Radwan-Pragłowska J., Janus Ł., Bogdał D., Matysek D., Cablik V. Microwave-assisted synthesis and characterization of chitosan aerogels doped with Au-NPs for skin regeneration. Polym. Test. 2019;73:366–376. doi: 10.1016/j.polymertesting.2018.11.024. DOI

Kallak T.K., Uvnäs-Moberg K. Oxytocin stimulates cell proliferation in vaginal cell line Vk2E6E7. Post Reprod. Health. 2017;23:6–12. doi: 10.1177/2053369117693148. PubMed DOI

Fan F.-Y., Chiu C.-C., Tseng C.-L., Lee H.-S., Pan Y.-N., Yang K.-C. Glycosaminoglycan/chitosan hydrogel for matrix-associated autologous chondrocyte implantation: An in vitro study. J. Med. Biol. Eng. 2014;34:211–217. doi: 10.5405/jmbe.1516. DOI