Nanostructured Capsules for Cartilage Tissue Engineering

  • Clara R. Correia
  • Rui L. Reis
  • João F. ManoEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1340)


Polymeric multilayered capsules (PMCs) have found great applicability in bioencapsulation, an evolving branch of tissue engineering and regenerative medicine. Here, we describe the production of hierarchical PMCs composed by an external multilayered membrane by layer-by-layer assembly of poly(l-lysine), alginate, and chitosan. The core of the PMCs is liquified and encapsulates human adipose stem cells and surface-functionalized collagen II-TGF-β3 poly(l-lactic acid) microparticles for cartilage tissue engineering.

Key words

Bioencapsulation Capsules Cartilage regeneration Collagen II Layer-by-layer Microparticles Stem cells Tissue engineering TGF-β3 



This work was financially supported by the Portuguese Foundation for Science and Technology (FCT) through the project PTDC/CTM-Bio/1814/2012 and Ph.D. grant with the reference no. SFRH/BD/69529/2010, co-financed by the Operational Human Potential Program (POPH), developed under the scope of the National Strategic Reference Framework (QREN) from the European Social Fund (FSE). The authors also acknowledge the financial support from Seventh Framework Programme of European Union (FP7/2007–2013) under grant agreement number REGPOT-CT2012-316331-POLARIS.


  1. 1.
    Decher G, Hong JD (1991) Buildup of ultrathin multilayer films by a self-assembly process, 1 consecutive adsorption of anionic and cationic bipolar amphiphiles on charged surfaces. Makromol Chem Macromol Symp 46:321–327CrossRefGoogle Scholar
  2. 2.
    Facca S, Cortez C, Mendoza-Palomares C et al (2010) Active multilayered capsules for in vivo bone formation. PNAS 107:3406–3411CrossRefGoogle Scholar
  3. 3.
    Mendes AC, Baran ET, Pereira RC et al (2012) Encapsulation and survival of a chondrocyte cell line within xanthan gum derivative. Macromol Biosci 12:350–359CrossRefGoogle Scholar
  4. 4.
    Ying Ma Y, Zhang Y, Liu Y (2013) Investigation of alginate-ε-poly-L-lysine microcapsules for cell microencapsulation. J Biomed Mater Res A 101:1265–1273Google Scholar
  5. 5.
    Tan W-H, Takeuchi S (2007) Monodisperse alginate hydrogel microbeads for cell encapsulation. Adv Mater 19:2696–2701CrossRefGoogle Scholar
  6. 6.
    Kim J, Arifin DR, Muja N (2011) Multifunctional capsule-in-capsules for immunoprotection and trimodal imaging. Angew Chem 123:2365–2369CrossRefGoogle Scholar
  7. 7.
    Hillberg AL, Kathirgamanathan K, Lam JBB (2013) Improving alginate-poly-L-ornithine-alginate capsule biocompatibility through genipin crosslinking. J Biomed Mater Res B Appl Biomater 101B:258–268CrossRefGoogle Scholar
  8. 8.
    Costa RR, Mano JF (2014) Polyelectrolyte multilayered assemblies in biomedical technologies. Chem Soc Rev. doi: 10.1039/c3cs60393h Google Scholar
  9. 9.
    Costa RR, Castro E, Arias FJ et al (2013) Multifunctional compartmentalized capsules with a hierarchical organization from the nano to the macro scales. Biomacromolecules 14:2403–2410CrossRefGoogle Scholar
  10. 10.
    Costa RR, Custódio CA, Arias FJ et al (2013) Nanostructured and thermoresponsive recombinant biopolymer-based microcapsules for the delivery of active molecules. Nanomedicine 9:895–902CrossRefGoogle Scholar
  11. 11.
    Caruso F, Caruso RA, Mohwald H (1998) Nanoengineering of inorganic and hybrid hollow spheres by colloidal templating. Science 282:1111–1114CrossRefGoogle Scholar
  12. 12.
    Donath E, Sukhorukov GB, Caruso F et al (1998) Novel hollow polymer shells by colloid-templated assembly of polyelectrolytes. Angew Chem Int Ed 37:2201–2205CrossRefGoogle Scholar
  13. 13.
    Costa NL, Sher P, Mano JF (2011) Liquefied capsules coated with multilayered polyelectrolyte films for cell immobilization. Adv Eng Mater 13:B218–B224CrossRefGoogle Scholar
  14. 14.
    Shchukin D, Sukhorukov G, Mohwald H (2003) Smart inorganic/organic nanocomposite hollow microcapsules. Angew Chem Int Ed 42:4472–4475CrossRefGoogle Scholar
  15. 15.
    Hernández RM, Orive G, Murua A et al (2010) Microcapsules and microcarriers for in situ cell delivery. Adv Drug Deliv Rev 62:711–730CrossRefGoogle Scholar
  16. 16.
    Brun-Graeppi AKAS, Richard C, Bessodes M et al (2011) Cell microcarriers and microcapsules of stimuli-responsive polymers. J Control Release 149:209–224CrossRefGoogle Scholar
  17. 17.
    Correia CR, Sher P, Reis RL et al (2013) Liquified chitosan–alginate multilayer capsules incorporating poly(L-lactic acid) microparticles as cell carriers. Soft Matter 9:2125–2130CrossRefGoogle Scholar
  18. 18.
    Correia CR, Reis RL, Mano JF (2013) Multilayered hierarchical capsules providing cell adhesion sites. Biomacromolecules 14:743–751CrossRefGoogle Scholar
  19. 19.
    Mahmoudifar N, Doran PM (2012) Chondrogenesis and cartilage tissue engineering: the longer road to technology development. Trends Biotechnol 30:166–176CrossRefGoogle Scholar
  20. 20.
    Madry H, Rey-Rico A, Venkatesan JK et al (2013) Transforming growth factor beta-releasing scaffolds for cartilage tissue engineering. Tissue Eng B Rev. doi: 10.1089/ten.teb.2013.0271 Google Scholar
  21. 21.
    Jones ME, Messersmith PB (2007) Facile coupling of synthetic peptides and peptide-polymer conjugates to cartilage via transglutaminase enzyme. Biomaterials 28:5215–5224CrossRefGoogle Scholar
  22. 22.
    Niger C, Beazley KE, Nurminskaya M (2013) Induction of chondrogenic differentiation in mesenchymal stem cells by TGF-beta cross-linked to collagen-PLLA [poly(L-lactic acid)] scaffold by transglutaminase 2. Biotechnol Lett 35:2193–2199CrossRefGoogle Scholar
  23. 23.
    Amali AJ, Awwad NH, Rana RK et al (2011) Nanoparticle assembled microcapsules for application as pH and ammonia sensor. Anal Chim Acta 708:75–83CrossRefGoogle Scholar
  24. 24.
    Kurayama F, Suzuki S, Oyamada T et al (2010) Facile method for preparing organic/inorganic hybrid capsules using amino-functional silane coupling agent in aqueous media. J Colloid Interface Sci 349:70–76CrossRefGoogle Scholar
  25. 25.
    Jean M, Alameh M, De Jesus D et al (2012) Chitosan-based therapeutic nanoparticles for combination gene therapy and gene silencing of in vitro cell lines relevant to type 2 diabetes. Eur J Pharm Sci 45:138–149CrossRefGoogle Scholar
  26. 26.
    Pujana MA, Pérez-Álvarez L, Iturbe LCC et al (2012) Water dispersible pH-responsive chitosan nanogels modified with biocompatible crosslinking-agents. Polymer 53:3107–3116CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Clara R. Correia
    • 1
    • 2
  • Rui L. Reis
    • 1
    • 2
  • João F. Mano
    • 1
    • 2
    Email author
  1. 1.3B’ s Research Group—Biomaterials, Biodegradables and BiomimeticsUniversity of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineGuimarãesPortugal
  2. 2.ICVS/3B’s—PT Government Associate LaboratoryGuimarães, BragaPortugal

Personalised recommendations