Biocompatible compositions based on chitosan and copolymer (lactide–titanium oxide) for engineering of tissue substitutes for wound healing


The optically transparent biocompatible, biodegradable, wound-healing materials were obtained based on chitosan and poly(lactide–titanium oxide). The optical transmittance of these films was more than 70% in the visible light region. The decreasing of the films transmittance by ~ 5–10% was observed under its UV irradiation as a result of the one-electron transition Ti4+ + e− ⇄ Ti3+. The tensile strength of the samples was up to 117 MPa. The investigation of the materials biocompatibility on experimental animals demonstrated the positive blood parameters and the absence of the inflammation process in the animals’ organisms, allergic reactions and stress after implantation of film and non-toxicity of the composite. The materials can be bioutilized and are biodegradable. The fibroblast cells (hTERT BY-5ta) adhesion and proliferation on the films surface were demonstrated in vitro. The films exhibited the UV-induced antibacterial properties.

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  1. 1.

    Peden M, Oyegbite K, Ozanne-Smith J et al (2008) World report on child injury prevention. World Health Organization, Switzerland

    Google Scholar 

  2. 2.

    Sheikh Z, Najeeb Sh, Khurshid Z, Verma V, Rashid H, Glogauer M (2015) Biodegradable materials for bone repair and tissue engineering applications. Materials 8:5744–5794.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Roslan AN (2013) Biodegradable films from poly (lactic acid) (PLA)-chitosan-polyethylene glycol (PEG): fabrication and evaluation of mechanical properties. UMP, Kuantan, Pahang

    Google Scholar 

  4. 4.

    Toncheva A, Spasova M, Paneva D, Manolova N, Rashkov I (2014) Polylactide (PLA)-based electrospun fibrous materials containing ionic drugs as wound dressing materials: a review. Int J Polym Mater Polym Biomater 63(13):657–671.

    CAS  Article  Google Scholar 

  5. 5.

    Pihlajamaki HK, Salminen ST, Tynninen O, Bostman OM, Laitinen O (2010) Tissue restoration after implantation of polyglycolide, polydioxanone, polylevolactide, and metallic pins in cortical bone: an experimental study in rabbits. Calcif Tissue Int 87:90–98.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Archana D, Singh BK, Dutta J, Dutta PK (2013) In vivo evaluation of chitosan–PVP–titanium dioxide nanocomposites as wound dressing material. Carbohydr Polym 95:530–539.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Poonguzhali R, Basha SK, Kumari VS (2017) Synthesis and characterization of chitosan-PVP-nanocellulose composites for in vitro wound dressing application. Int J Biol Macromol 105:111–120.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Stagnaro P, Schizzi I, Utzeri R, Marsano E, Castellano M (2018) Alginate-polymethacrylate hybrid hydrogels for potential osteochondral tissue regeneration. Carbohydr Polym 185:56–62.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Kailani MH, Jafar H, Awidi A (2016) Synthetic biomaterials for skin tissue engineering. In: Albanna MZ, James H (eds) Skin tissue engineering and regenerative medicine. Academic Press, London, pp 163–183

    Google Scholar 

  10. 10.

    Chena Q, Bruyneel A, Carr C, Czernuszka J (2013) Bio-mechanical properties of novel bi-layer collagen-elastin scaffolds for heart valve tissue engineering. Procedia Eng 59:247–254.

    CAS  Article  Google Scholar 

  11. 11.

    Barenghi R, Beke S, Romano I, Gavazzo P, Vassalli Farkas B, Brandi F, Scaglione S (2014) Elastin-coated biodegradable photopolymer scaffolds for tissue engineering applications. Biomed Res Int.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    León-Mancilla BH, Araiza-Téllez MA, Flores-Flores JO, Pina-Barba MC (2016) Physico-chemical characterization of collagen scaffolds for tissue engineering. J Appl Res Technol 14:77–85.

    Article  Google Scholar 

  13. 13.

    Fan X, Chen C, Hea X, Li N, Huanga J, Tang K, Li Y, Wang F (2016) Nano-TiO2/collagen-chitosan porous scaffold for wound repairing. Int J Biol Macromol 91:15–22.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Bitar KN, Raghavan S, Zakhem E (2014) Tissue engineering in the gut: developments in neuro musculature. Gastroenterology 146(7):1614–1624.

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Karimi A, Navidbakhsh M, Faghihi S (2014) Fabrication and mechanical characterization of a polyvinyl alcohol sponge for tissue engineering applications. Perfusion 29(3):231–237.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Kim J, Lee CM (2017) Wound healing potential of a polyvinyl alcohol-blended pectin hydrogel containing Hippophae rahmnoides L. extract in a rat model. Int J Biol Macromol 99:586–593.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Golafshan N, Rezahasani R, Esfahani TM, Kharaziha M, Khorasani SN (2017) Nanohybrid hydrogels of laponite: PVA-alginate as a potential wound healing material. Carbohydr Polym 176(15):392–401

    CAS  Article  Google Scholar 

  18. 18.

    Venkatesan J, Bhatnagar I, Manivasagan P, Kanga KH, Kim SK (2015) Alginate composites for bone tissue engineering: a review. Int J Biol Macromol 72:269–281.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Hancı D, Altun H (2015) Effectiveness of hyaluronic acid in post-tonsillectomy pain relief and wound healing: a prospective, double-blind, controlled clinical study. Int J Pediatric Otorhinol 79(9):1388–1392.

    Article  Google Scholar 

  20. 20.

    Dahlgren LA, Milton SC, Boswell SG, Werre SR, Brewster CC, Jones CS, Crisman MK (2016) Evaluation of a hyaluronic acid-based biomaterial to enhance wound healing in the equine distal limb. J Equine Vet Sci 44:90–99.

    Article  Google Scholar 

  21. 21.

    Dai T, Tanaka M, Huang Y-Y, Hamblin MR (2011) Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects. Expert Rev Anti Infect Ther 9(7):857–879.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Ahmed Sh, Ali AA, Sheikh J (2018) A review on chitosan centred scaffolds and their applications in tissue engineering. Int J Biol Macromol 116:849–862.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Samadi S, Moradkhani M, Beheshti B, Irani M (2018) Aliabadi M (2018) Fabrication of chitosan/poly(lactic acid)/grapheme oxide/TiO2 composite nanofibrous scaffolds for sustained delivery of doxorubicin and treatment of lung cancer. Int J Biol Macromol 110:416–424.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Balagangadharan K, Dhivya S (2017) Selvamurugan N (2017) Chitosan based nanofibers in bone tissue engineering. Int J Bio Macromol 104:1372–1382.

    CAS  Article  Google Scholar 

  25. 25.

    Jennings JA, Bumgardner JD (2017) Chitosan based biomaterials: fundamentals, vol 1. Woodhead Publishing, Cambridge.

    Google Scholar 

  26. 26.

    Miguel SP, Moreira AF, Correia IJ (2019) Chitosan based-asymmetric membranes for wound healing: a review. Int J Biol Macromol 127:460–475.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Biranje SS, Madiwale PV, Patankar KC, Chhabra R, Dandekar-Jain P, Adivarekar RV (2019) Hemostasis and anti-necrotic activity of wound-healing dressing containing chitosan nanoparticles. Int J Biol Macromol 121:936–946.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Liu X, Niu Y, Chen KC, Chen Sh (2017) Rapid hemostatic and mild polyurethane-urea foam wound dressing for promoting wound healing. Mat Sci Eng C 71:289–297.

    CAS  Article  Google Scholar 

  29. 29.

    Lee SM, Park IK, Kim YS, Kim HJ, Moon H, Mueller S, Jeong Y-I (2016) Physical, morphological, and wound healing properties of a polyurethane foam-film dressing. Biomater Res 20:15–26.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Rinaudo M (2006) Chitin and chitosan: properties and applications. Prog Polym Sci 31:603–632.

    CAS  Article  Google Scholar 

  31. 31.

    Chang SH, Lin HT, Wu GJ, Tsai GJ (2015) pH Effects on solubility, zeta potential, and correlation between antibacterial activity and molecular weight of chitosan. Carbohydr Polym 134:74–81.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Kim S-E (2010) Chitin, chitosan, oligosaccharides and their derivatives: biological activities and applications, 1st edn. CRC Press, London

    Google Scholar 

  33. 33.

    Muzzarelli RAA (2009) Chitins and chitosans for the repair of wounded skin, nerve, cartilage and bone. Carbohydr Polym 76:167–182.

    CAS  Article  Google Scholar 

  34. 34.

    Smith AM, Moxon S, Morris GA (2016) Biopolymers as wound healing materials. Wound Healing Biomater 2:261–287.

    Article  Google Scholar 

  35. 35.

    Farah S, Anderson DG, Langer R (2016) Physical and mechanical properties of PLA, and their functions in widespread applications—a comprehensive review. Adv Drug Deliv Rev 107:367–392.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Kean T, Thanou M (2010) Biodegradation, biodistribution and toxicity of chitosan. Adv Drug Deliv Rev 62(1):3–11.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Park SY, Park HJ, Lin XQ, Sano Y (2000) Characterization of chitosan film and structure in solution. Hydrocolloids 1:199–204.

    CAS  Article  Google Scholar 

  38. 38.

    Pippi P (2017) Post-surgical clinical monitoring of soft tissue wound healing in periodontal and implant surgery. Int J Med Sci 14(8):721–728.

    Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Smith JK, Bumgardner JD, Courtney HS, Smeltzer MS, Haggard WO (2010) J Biomed Mater Res B Appl Biomater 94(1):203–211.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Guo S, DiPietro LA (2010) Factors affecting wound healing. J Dent Res 89(3):219–229.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Fujishima A, Zhang X, Tryk D (2007) Heterogeneous photocatalysis: from water photolysis to applications in environmental clean up. Int J Hydrog Energy 14:2664–2672.

    CAS  Article  Google Scholar 

  42. 42.

    Behera SS, Das U, Kumar A, Bissoyi A, Singh AK (2017) Chitosan/TiO2 composite membrane improves proliferation and survival of L929 fibroblast cells: application in wound dressing and skin regeneration. Int J Biol Macromol 98:329–340.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Srikanth B, Goutham R, Narayan RB, Ramprasath A, Gopinath KP, Sankaranarayanan AR (2017) Recent advancements in supporting materials for immobilised photocatalytic applications in waste water treatment. J Environ Manag 200:60–78.

    CAS  Article  Google Scholar 

  44. 44.

    Fujishima A, Rao TN, Tryk DA (2000) Titanium dioxide photocatalysis. J Photochem Photobiol C Photochem Rev 1:1–21

    CAS  Article  Google Scholar 

  45. 45.

    Ahmed AY, Kandiel TA, Oekermann T (2011) Photocatalytic activities of different well-defined crystal TiO2 surfaces: anatase versus rutile. J Phys Chem Lett 2:2461–2465.

    CAS  Article  Google Scholar 

  46. 46.

    Volchegorskii IA, Nalimov AG, Iarovinskii BG, Lifshits RI (1989) Comparison of various approaches to the determination of the products of lipid peroxidation in heptane-isopropanol extracts of blood. Vopr Med Khim 35:127–131

    CAS  PubMed  Google Scholar 

  47. 47.

    Lvovskaya EI, Volchegorsky IA, Shemyarov SE (1991) Spectrophometric estimation of the final lipoperoxidation products. Vopr Med Chem 4:92–93 (In Russian, English abstract)

    Google Scholar 

  48. 48.

    Glantz SA (2012) Primer of biostatistics, Seven edn. McGraw-Hill, New York, p 327

    Google Scholar 

  49. 49.

    Liu Zh-T, Li Ch-Y, Chen J-D, Liu W-L, Tsai Ch-Y, Ko B-T (2017) Titanium, aluminum and zinc complexes containing diamine-bis(benzotriazole phenolate) ligands: synthesis, structural characterization and catalytic studies for ring-opening polymerization of ε-caprolactone. J Mol Struct 1134:395–403.

    CAS  Article  Google Scholar 

  50. 50.

    Cheshmedzhieva D, Angelova I, Ilieva S, Georgiev GS, Galabov B (2012) Initiation of ring-opening polymerization of lactide: the effect of metal alkoxide catalyst. Comput Theor Chem 995:8–16.

    CAS  Article  Google Scholar 

  51. 51.

    Li W, Zhang Ch, Chi H, Li L, Lan T, Han P, Chen H, Qin Y (2017) Development of antimicrobial packaging film made from poly(lactic acid) incorporating titanium dioxide and silver nanoparticles. Molecules 22(7):1170–1185.

    CAS  Article  PubMed Central  Google Scholar 

  52. 52.

    Kim Y, Verkade JG (2005) Living polymerization of lactide using titanium alkoxide catalysts. Macromol Symp 224(1):105–118.

    CAS  Article  Google Scholar 

  53. 53.

    Salomatina EV, Bityurin NM, Gulenova MV et al (2013) Synthesis, structure, and properties of organic–inorganic nanocomposites containing poly(titanium oxide). J Mater Chem C 39(1):6375–6385.

    CAS  Article  Google Scholar 

  54. 54.

    Liao H-T, Wu Ch-S (2008) New biodegradable blends prepared from polylactide, titanium tetraisopropylate, and starch. J App Polym Sci 108(4):2280–2289.

    CAS  Article  Google Scholar 

  55. 55.

    Chiang PC, Whang WT (2003) The synthesis and morphology characteristic study of BAO-ODPA polyimide/TiO2 nano hybrid films. Polymer 44:2249–2254.

    CAS  Article  Google Scholar 

  56. 56.

    Shao PL, Mauritz KA, Moore RB (1996) Perfluorosulfonate ionomer]/[SiO2-TiO2] nanocomposites via polymer in situ sol-gel chemistry: sequential alkoxide procedure. J Polym Sci Part B Polym Phys 34:873–882.;2-N

    CAS  Article  Google Scholar 

  57. 57.

    Gallagher AJ, Anniadh AN, Bruyere K, Otténio M, Xie H, Gilchrist MD (2012) Dynamic tensile properties of human skin. In: IRCOBI conference IRC-12-59, pp 494–502

  58. 58.

    Joodaki H, Panzer MB (2018) Skin mechanical properties and modeling: a review. Proc Inst Mech Eng [H] 232(4):323–343.

    Article  Google Scholar 

  59. 59.

    Bain BJ (2008) Blood cells: a practical guide, 4th edn. Wiley-Blackwell, Willey

    Google Scholar 

  60. 60.

    Shurygina IA, Shurygin MG, Ayushinova NI, Kanya OV (2012) Fibroblasts and their role in the development of connective tissue. Sib Med J (Irkutsk) 3:8–12

    Google Scholar 

  61. 61.

    Howling GI, Dettmar PW, Goddard PA, Hampson FC, Dornish M, Wood EJ (2001) The effect of chitin and chitosan on the proliferation of human skin fibroblasts and keratinocytes in vitro. Biomaterials 22:2959–2966.

    CAS  Article  PubMed  Google Scholar 

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This work was carried out with financial supporting of the Ministry of Education and Science of the Russian Federation (Contract No. 4.3760.2017/PCh).

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Correspondence to L. A. Smirnova.

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Salomatina, E.V., Lednev, I.R., Silina, N.E. et al. Biocompatible compositions based on chitosan and copolymer (lactide–titanium oxide) for engineering of tissue substitutes for wound healing. Polym. Bull. 77, 5083–5101 (2020).

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  • Chitosan
  • Poly(lactide–titanium oxide)
  • Biocompatible materials
  • Antibacterial properties
  • Fibroblast adhesion