Skip to main content

Advertisement

SpringerLink
Log in

Quaternised chitosan composites with in situ precipitated nano calcium phosphate for making bioactive and degradable tissue engineering scaffolds

  • Original Paper
  • Published:
Journal of Polymer Research Aims and scope Submit manuscript

Abstract

Bioactive composites of chitosan with calcium phosphate mineral particles are considered good platform for guided bone regeneration (GBR) scaffolds. Obtaining uniform distribution of particles in the scaffold is a challenge because during the compositing process, the acidic nature of chitosan affects the stability of calcium phosphate particles. This work presents a viable process to obtain chitosan based porous scaffold with uniformly distributed nanoparticles of calcium phosphates. The base material is prepared by quaternizing chitosan (QC) so that it forms a solution in the neutral pH. QC solution is supersaturated with calcium and phosphate ions before lyophilizing to make thin porous sheets. Subjecting the sheet to ammonia treatment will precipitate calcium phosphate nanoparticles homogeneously in the mass. The composition and micromorphology of the composite were characterized. Tensile strength, water uptake and degradation of the material were determined in vitro. In the in vitro bioactivity test using simulated body fluid, the composite showed apatitic layer on the surface. The material passed the criteria of in vitro cytocompatibility, and showed good adhesion with human periodontal ligament cells. The mechanical properties, bioactivity, cytocompatibility and cell response of the quaternised chitosan composite with nano calcium phosphate, suggest its use as GBR scaffolds.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16

Similar content being viewed by others

References

  1. Pradhan S, Brooks AK, Yadavalli VK (2020) Nature-derived materials for the fabrication of functional biodevices. Materials Today Bio 7:100065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Pang Y, Qin A, Lin X, Yang L, Wang Q, Wang Z, Shan Z, Li S, Wang J, Fan S, Hu Q (2017) Biodegradable and biocompatible high elastic chitosan scaffold is cell-friendly both in vitro and in vivo. Oncotarget 8:35583

    Article  PubMed  PubMed Central  Google Scholar 

  3. Tao F, Cheng Y, Shi X, Zheng H, Du Y, Xiang W, Deng H (2020) Applications of chitin and chitosan nanofibers in bone regenerative engineering. Carbohyd Polym 230:115658

    Article  CAS  Google Scholar 

  4. Cheung RC, Ng TB, Won JH, Chan WY (2015) Chitosan: an update on potential biomedical and pharmaceutical applications. Mar Drugs 13:5156–5186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Foster LJ, Ho S, Hook J, Basuki M, Marcal H (2015) Chitosan as a biomaterial: Influence of degree of deacetylation on its physiochemical, material and biological properties. PLoS ONE 10:e0135153

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Zhou Y, Gao HL, Shen LL, Pan Z, Mao LB, Wu T, He JC, Zou DH, Zhang ZY, Yu SH (2016) Chitosan microspheres with an extracellular matrix-mimicking nanofibrous structure as cell-carrier building blocks for bottom-up cartilage tissue engineering. Nanoscale 8:309–317

    Article  CAS  PubMed  Google Scholar 

  7. Jiang Y, Deng Y, Tu Y, Ay B, Sun X, Li Y, Wang X, Chen X, Zhang L (2019) Chitosan-based asymmetric topological membranes with cell-like features for healthcare applications. J Mater Chem B 7:2634–2642

    Article  CAS  PubMed  Google Scholar 

  8. Szymańska E, Winnicka K (2015) Stability of chitosan—a challenge for pharmaceutical and biomedical applications. Mar Drugs 13:1819–1846

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Rodríguez-Vázquez M, Vega-Ruiz B, Ramos-Zúñiga R, Saldaña-Koppel DA, Quiñones-Olvera, LF (2015) Chitosan and its potential use as a scaffold for tissue engineering in regenerative medicine. BioMed Res Int

  10. Madera-Santana TJ, Herrera-Méndez CH, Rodríguez-Núñez JR (2018) An overview of the chemical modifications of chitosan and their advantages. Green Materials 6:131–142

    Article  Google Scholar 

  11. Brasselet C, Pierre G, Dubessay P, Dols-Lafargue M, Coulon J, Maupeu J, Vallet-Courbin A, De Baynast H, Doco T, Michaud P, Delattre C (2019) Modification of chitosan for the generation of functional derivatives. Appl Sci 9:1321

    Article  CAS  Google Scholar 

  12. Cho J, Grant J, Piquette-Miller M, Allen C (2006) Synthesis and physicochemical and dynamic mechanical properties of a water-soluble chitosan derivative as a biomaterial. Biomacromol 7:2845–2855

    Article  CAS  Google Scholar 

  13. Luo Y, Wang Q (2014) Recent development of chitosan-based polyelectrolyte complexes with natural polysaccharides for drug delivery. Int J Biol Macromol 64:353–367

    Article  CAS  PubMed  Google Scholar 

  14. Zhang Y, Zhang M (2001) Synthesis and characterization of macroporous chitosan/calcium phosphate composite scaffolds for tissue engineering. J Biomed Mater Res: An Official J Soc Biomater, The Japanese Soc Biomater, and The Australian Soci Biomater and the Korean Soc Biomater 55:304–312

    Article  CAS  Google Scholar 

  15. Yokogawa Y, Nishizawa K, Nagata F, Kameyama T (2001) Bioactive Properties of Chitin/Chitosan—Calcium Phosphate Composite Materials. J Sol-Gel Sci Technol 21:105–113

    Article  CAS  Google Scholar 

  16. Salama A (2021) Recent progress in preparation and applications of chitosan/calcium phosphate composite materials. Int J Biol Macromol 178:240–252

    Article  CAS  PubMed  Google Scholar 

  17. Guo S, He L, Yang R, Chen B, Xie X, Jiang B, Weidong T, Ding Y (2020) Enhanced effects of electrospun collagen-chitosan nanofiber membranes on guided bone regeneration. J Biomater Sci Polym Ed 31:155–168

    Article  CAS  PubMed  Google Scholar 

  18. Ma S, Chen Z, Qiao F, Sun Y, Yang X, Deng X, Cen L, Cai Q, Wu M, Zhang X, Gao P (2014) Guided bone regeneration with tripolyphosphate cross-linked asymmetric chitosan membrane. J Dent 42:1603–1612

    Article  CAS  PubMed  Google Scholar 

  19. Lee EJ, Shin DS, Kim HE, Kim HW, Koh YH, Jang JH (2009) Membrane of hybrid chitosan–silica xerogel for guided bone regeneration. Biomaterials 30:743–750

    Article  CAS  PubMed  Google Scholar 

  20. Ramesh S, Lungaro L, Tsikritsis D, Weflen E, Rivero IV, Elfick AP (2018) Fabrication and evaluation of poly (lactic acid), chitosan, and tricalcium phosphate biocomposites for guided bone regeneration. J Appl Polym Sci 135:46692

    Article  CAS  Google Scholar 

  21. Chen TW, Chang SJ, Niu GC, Hsu YT, Kuo SM (2006) Alginate-coated chitosan membrane for guided tissue regeneration. J Appl Polym Sci 102:4528–4534

    Article  CAS  Google Scholar 

  22. Polo-Corrales L, Latorre-Esteves M, Ramirez-Vick JE (2014) Scaffold design for bone regeneration. J Nanosci Nanotechnol 14:15–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Islam MM, Shahruzzaman M, Biswas S, Rashid SMN, TU, (2020) Chitosan based bioactive materials in tissue engineering applications-A review. Bioactive materials 5:164–183

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kong L, Gao Y, Lu G, Gong Y, Zhao N, Zhang X (2006) A study on the bioactivity of chitosan/nano-hydroxyapatite composite scaffolds for bone tissue engineering. Eur Polymer J 42:3171–3179

    Article  CAS  Google Scholar 

  25. Li X, Nan K, Shi S, Chen H (2012) Preparation and characterization of nano-hydroxyapatite /chitosan cross-linking composite membrane intended for tissue engineering. Int J Biol Macromol 50:43–49

    Article  CAS  PubMed  Google Scholar 

  26. Jeong J, Kim JH, Shim JH, Hwang NS, Heo CY (2019) Bioactive calcium phosphate materials and applications in bone regeneration. Biomaterials research 23:1–1

    Article  CAS  Google Scholar 

  27. Alizadeh-Osgouei M, Li Y, Wen C (2019) A comprehensive review of biodegradable synthetic polymer-ceramic composites and their manufacture for biomedical applications. Bioactive materials 4:22–36

    Article  PubMed  Google Scholar 

  28. Rogina A, Rico P, Ferrer GG, Ivanković M, Ivanković H (2015) Effect of in situ formed hydroxyapatite on microstructure of freeze-gelled chitosan-based biocomposite scaffolds. Eur Polymer J 68:278–287

    Article  CAS  Google Scholar 

  29. Puvvada YS, Vankayalapati S, Sukhavasi S (2012) Extraction of chitin from chitosan from exoskeleton of shrimp for application in the pharmaceutical industry. Intl Curr Pharmaceut J 1:258–263

    Article  CAS  Google Scholar 

  30. Cui D, Szarpak A, Pignot-Paintrand I, Varrot A, Boudou T, Detrembleur C, Jérôme C, Picart C, Auzély-Velty R (2010) Contact-Killing Polyelectrolyte Microcapsules Based on Chitosan Derivatives. Adv Funct Mater 20:3303–3312

    Article  CAS  Google Scholar 

  31. Rajeswari Krishnankutty A, Najeema Sulaiman S, Sadasivan A, Joseph R, Komath M (2022) Porous membranes of quaternized chitosan composited with strontium-based nanobioceramic for periodontal tissue regeneration. J Biomater Appl 36:1254–1268

    Article  CAS  PubMed  Google Scholar 

  32. Czechowska-Biskup R, Jarosińska D, Rokita B, Ulański P, Rosiak JM (2012) Determination of degree of deacetylation of chitosan-comparision of methods. Prog Chem App Chitin Deriv 17:5–20

    CAS  Google Scholar 

  33. Hirai A, Odani H, Nakajima A (1991) Determination of degree of deacetylation of chitosan by 1H NMR spectroscopy. Polym Bull 26:87–94

    Article  CAS  Google Scholar 

  34. ASTM International (2011) F2103–11 Standard Guide for Characterization and Testing of Chitosan Salts as Starting Materials Intended for Use in Biomedical and Tissue-Engineered Medical Product Applications; ASTM International: West Conshohocken. PA, USA

    Google Scholar 

  35. Kara A, Tamburaci S, Tihminlioglu F, Havitcioglu H (2019) Bioactive fish scale incorporated chitosan biocomposite scaffolds for bone tissue engineering. Int J Biol Macromol 130:266–79

  36. Sun T, Khan TH, Sultana N (2014) Fabrication and in vitro evaluation of nanosized hydroxyapatite /chitosan-based tissue engineering scaffolds. J Nanomater

  37. Kokubo T, Takadama H (2006) How useful is SBF in predicting in vivo bone bioactivity? Biomaterials 27:2907–2915

    Article  CAS  PubMed  Google Scholar 

  38. Pereda M, Ponce AG, Marcovich NE, Ruseckaite RA, Martucci JF (2011) Chitosan-gelatin composites and bi-layer films with potential antimicrobial activity. Food Hydrocolloids 24:1372–1381

    Article  CAS  Google Scholar 

  39. Vogel AI, Mendham J (2000) Vogel’s textbook of quantitative chemical analysis. Prentice Hall, Harlow

    Google Scholar 

  40. Das EC, Kumary TV, Anil Kumar PR, Komath M (2019) Calcium sulfate-based bioactive cement for periodontal regeneration: An in vitro study. Indian J Dent Res 30:558–567

    Article  PubMed  Google Scholar 

  41. Xianmiao C, Yubao L, Yi Z, Li Z, Jidong L, Huanan W (2009) Properties and in vitro biological evaluation of nano-hydroxyapatite/chitosan membranes for bone guided regeneration. Mater Sci Eng, C 29:29–35

    Article  CAS  Google Scholar 

  42. Kalsi PS (2007) In Spectroscopy of organic compounds. New Age International

  43. Song H, Wu H, Li S, Tian H, Li Y, Wang J (2018) Homogeneous synthesis of cationic chitosan via new avenue. Molecules 23:1921

    Article  PubMed Central  CAS  Google Scholar 

  44. Rhim JW, Lee JH, Ng PK (2007) Mechanical and barrier properties of biodegradable soy protein isolate-based films coated with polylactic acid. LWT-Food Sci Technol 40:232–238

    Article  CAS  Google Scholar 

  45. LogithKumar R, KeshavNarayan A, Dhivya S, Chawla A, Saravanan S, Selvamurugan N (2016) A review of chitosan and its derivatives in bone tissue engineering. Carbohyd Polym 151:172–188

    Article  CAS  Google Scholar 

  46. Wu QX, Lin DQ, Yao SJ (2014) Design of chitosan and its water soluble derivatives-based drug carriers with polyelectrolyte complexes. Mar Drugs 12:6236–6253

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Mourya VK, Inamdar NN (2008) Chitosan-modifications and applications: opportunities galore. React Funct Polym 68:1013–1015

    Article  CAS  Google Scholar 

  48. Yousefi AM, Oudadesse H, Akbarzadeh R, Wers E, Lucas-Girot A (2014) Physical and biological characteristics of nanohydroxyapatite and bioactive glasses used for bone tissue engineering. Nanotechnol Rev 3:527–552

    Article  CAS  Google Scholar 

  49. Fu S, Sun Z, Huang P, Li Y, Hu N (2019) Some basic aspects of polymer nanocomposites: A critical review. Nano Materials Science 1:2–30

    Article  Google Scholar 

  50. Mekmene O, Quillard S, Rouillon T, Bouler JM, Piot M, Gaucheron F (2009) Effects of pH and Ca/P molar ratio on the quantity and crystalline structure of calcium phosphates obtained from aqueous solutions. Dairy Sci Technol 89:301–316

    Article  CAS  Google Scholar 

  51. Binitha MP (2013) Dielectric Property Studies of Biologically Compatible Brushite Single Crystals Used as Bone Graft Substitute. J Biomater Nanobiotechnol 4:119–122

    Article  CAS  Google Scholar 

  52. Peter M, Binulal NS, Nair SV, Selvamurugan N, Tamura H, Jayakumar R (2010) Novel biodegradable chitosan–gelatin/nano-bioactive glass ceramic composite scaffolds for alveolar bone tissue engineering. Chem Eng J 158:353–361

    Article  CAS  Google Scholar 

  53. Li XY, Nan KH, Shi S, Chen H (2012) Preparation and characterization of nanohydroxyapatite /chitosan cross-linking composite membrane intended for tissue engineering. Int J Biol Macromol 50:43–49

    Article  CAS  PubMed  Google Scholar 

  54. Qasim SB, Delaine-Smith RM, Fey T, Rawlinson A, Rehman IU (2015) Freeze gelated porous membranes for periodontal tissue regeneration. Actabiomaterialia 23:317–328

    CAS  Google Scholar 

  55. Bachir AI, Horwitz AR, Nelson WJ, Bianchini JM (2017) Actin-Based Adhesion Modules Mediate Cell Interactions with the Extracellular Matrix and Neighbouring Cells. Cold Spring Harb Perspect Biol 9:a023234

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the Director and the Head, Biomedical Technology Wing of SCTIMST for providing facilities for this work. The first author (RK Adarsh) acknowledges the fellowship provided by Department of Biotechnology, Government of India, from the project No.BT/PR14704. Authors also express thanks to Dr. H.K.Varma, Dr. Roy Joseph, Dr. Renjith, Dr. S. Suresh Babu, Dr. K.V. Nishad, Dr. Deepu, Dr. Amritha Nadarajan, Ms Nimi N. of SCTIMST and Dr Kana M Sureshan‬ (IISER) for technical support.‬‬‬‬‬‬‬‬

Author information

Authors and Affiliations

  1. Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, 695012, India

    R. K. Adarsh, Eva C. Das, Gopika V. Gopan, Remya K. Rajan & Manoj Komath

Authors
  1. R. K. Adarsh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eva C. Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gopika V. Gopan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Remya K. Rajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Manoj Komath
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manoj Komath.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Below is the link to the electronic supplementary material.

Supplementary file1 (TIF 8976 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Adarsh, R.K., Das, E.C., Gopan, G.V. et al. Quaternised chitosan composites with in situ precipitated nano calcium phosphate for making bioactive and degradable tissue engineering scaffolds. J Polym Res 29, 267 (2022). https://doi.org/10.1007/s10965-022-03125-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10965-022-03125-z

Keywords

Search

Navigation