A biomimetic honeycomb-like scaffold prepared by flow-focusing technology for cartilage regeneration

Chen Chie Wang, Kai Chiang Yang, Keng Hui Lin, Chang Chin Wu, Yen Liang Liu, Feng Huei Lin, Ing Ho Chen

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


A tissue engineering chondrocytes/scaffold construct provides a promise to cartilage regeneration. The architecture of a scaffold such as interconnections, porosities, and pore sizes influences the fates of seeding cells including gene expression, survival, migration, proliferation, and differentiation thus may determine the success of this approach. Scaffolds of highly ordered and uniform structures are desirable to control cellular behaviors. In this study, a newly designed microfluidic device based on flow-focusing geometry was developed to fabricate gelatin scaffolds of ordered pores. In comparison with random foam scaffolds made by the conventional freeze-dried method, honeycomb-like scaffolds exhibit higher swelling ratio, porosity, and comparable compressive strength. In addition, chondrocytes grown in the honeycomb-like scaffolds had good cell viability, survival rate, glycosaminoglycans production, and a better proliferation than ones in freeze-dried scaffolds. Real-time PCR analysis showed that the mRNA expressions of aggrecan and collagen type II were up-regulated when chondrocytes cultured in honeycomb-like scaffolds rather than cells cultured as monolayer fashion. Oppositely, chondrocytes expressed collagen type II as monolayer culture when seeded in freeze-dried scaffolds. Histologic examinations revealed that cells produced proteoglycan and distributed uniformly in honeycomb-like scaffolds. Immunostaining showed protein expression of S-100 and collagen type II but negative for collagen type I and X, which represents the chondrocytes maintained normal phenotype. In conclusion, a highly ordered and honeycomb-like scaffold shows superior performance in cartilage tissue engineering. Biotechnol. Bioeng. 2014;111: 2338-2348.

A: Two gelatin scaffolds prepared by the microfluidic device. B: Uniform bubbles were generated and collected. C: Confocal microscopy showed the microbubbles self-assembled layer by layer, (D) reconstituting a highly organized 3D ordered array with a highly organized honeycomb-like structure. E: Confocal microscopy also showed the microfluidic scaffold had an interconnecting porous structure.

Original languageEnglish
Pages (from-to)2338-2348
Number of pages11
JournalBiotechnology and Bioengineering
Issue number11
Publication statusPublished - Nov 1 2014


  • Cartilage tissue engineering
  • Flow-focusing
  • Gelatin
  • Microfluidic
  • Scaffold

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Medicine(all)


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