Enzymatically fabricated and degradable microcapsules for production of multicellular spheroids with well-defined diameters of less than 150 μm

Shinji Sakai, Sho Ito, Yuko Ogushi, Ichiro Hashimoto, Natsuko Hosoda, Yoshinori Sawae, Koei Kawakami

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Microcapsules with a single, spherical hollow core less than 150 μm in diameter were developed to obtain multicellular spheroids with well-defined sizes of less than 150 μm in diameter. An aqueous solution of phenolic hydroxyl derivative of carboxymethylcellulose (CMC-Ph) containing human hepatoma cell line (HepG2) cells and horse radish peroxidase (HRP) was injected into a coflowing stream of liquid paraffin, containing H2O2, resulting in cell-enclosing CMC-Ph microparticles, 135 μm in diameter, via a peroxidase-catalyzed crosslinking reaction. The CMC-Ph microparticles were then coated with a phenolic hydroxyl derivative of alginate (Alg-Ph) gel membrane several dozen micrometers in thickness, crosslinked via the same enzymatic reaction process, followed by further crosslinking between the carboxyl groups of alginate by Sr2+. A hollow core structure was achieved by immersing the resultant microcapsules in a medium containing cellulase, which degrades the enclosed CMC-Ph microparticles. The HepG2 cells in the microcapsules then grew and completely filled the hollow core. Multicellular spheroids the same size as the CMC-Ph microparticles, with living cells at their outer surface, were collected within 1 min by soaking them in a medium containing alginate lyase to degrade the Alg-Ph gel microcapsule membrane.

Original languageEnglish
Pages (from-to)5937-5942
Number of pages6
JournalBiomaterials
Volume30
Issue number30
DOIs
Publication statusPublished - Oct 1 2009

Fingerprint

Cellular Spheroids
Alginate
Capsules
Crosslinking
Gels
Cells
Hydroxyl Radical
Peroxidase
Derivatives
Membranes
Mineral Oil
Hep G2 Cells
Paraffins
Carboxymethylcellulose Sodium
Cellulase
Raphanus
Liquids
Hepatocellular Carcinoma
Cell Line
alginic acid

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Enzymatically fabricated and degradable microcapsules for production of multicellular spheroids with well-defined diameters of less than 150 μm. / Sakai, Shinji; Ito, Sho; Ogushi, Yuko; Hashimoto, Ichiro; Hosoda, Natsuko; Sawae, Yoshinori; Kawakami, Koei.

In: Biomaterials, Vol. 30, No. 30, 01.10.2009, p. 5937-5942.

Research output: Contribution to journalArticle

Sakai, Shinji ; Ito, Sho ; Ogushi, Yuko ; Hashimoto, Ichiro ; Hosoda, Natsuko ; Sawae, Yoshinori ; Kawakami, Koei. / Enzymatically fabricated and degradable microcapsules for production of multicellular spheroids with well-defined diameters of less than 150 μm. In: Biomaterials. 2009 ; Vol. 30, No. 30. pp. 5937-5942.
@article{ffc642dfe2e243a0b7322567420111e6,
title = "Enzymatically fabricated and degradable microcapsules for production of multicellular spheroids with well-defined diameters of less than 150 μm",
abstract = "Microcapsules with a single, spherical hollow core less than 150 μm in diameter were developed to obtain multicellular spheroids with well-defined sizes of less than 150 μm in diameter. An aqueous solution of phenolic hydroxyl derivative of carboxymethylcellulose (CMC-Ph) containing human hepatoma cell line (HepG2) cells and horse radish peroxidase (HRP) was injected into a coflowing stream of liquid paraffin, containing H2O2, resulting in cell-enclosing CMC-Ph microparticles, 135 μm in diameter, via a peroxidase-catalyzed crosslinking reaction. The CMC-Ph microparticles were then coated with a phenolic hydroxyl derivative of alginate (Alg-Ph) gel membrane several dozen micrometers in thickness, crosslinked via the same enzymatic reaction process, followed by further crosslinking between the carboxyl groups of alginate by Sr2+. A hollow core structure was achieved by immersing the resultant microcapsules in a medium containing cellulase, which degrades the enclosed CMC-Ph microparticles. The HepG2 cells in the microcapsules then grew and completely filled the hollow core. Multicellular spheroids the same size as the CMC-Ph microparticles, with living cells at their outer surface, were collected within 1 min by soaking them in a medium containing alginate lyase to degrade the Alg-Ph gel microcapsule membrane.",
author = "Shinji Sakai and Sho Ito and Yuko Ogushi and Ichiro Hashimoto and Natsuko Hosoda and Yoshinori Sawae and Koei Kawakami",
year = "2009",
month = "10",
day = "1",
doi = "10.1016/j.biomaterials.2009.07.031",
language = "English",
volume = "30",
pages = "5937--5942",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
number = "30",

}

TY - JOUR

T1 - Enzymatically fabricated and degradable microcapsules for production of multicellular spheroids with well-defined diameters of less than 150 μm

AU - Sakai, Shinji

AU - Ito, Sho

AU - Ogushi, Yuko

AU - Hashimoto, Ichiro

AU - Hosoda, Natsuko

AU - Sawae, Yoshinori

AU - Kawakami, Koei

PY - 2009/10/1

Y1 - 2009/10/1

N2 - Microcapsules with a single, spherical hollow core less than 150 μm in diameter were developed to obtain multicellular spheroids with well-defined sizes of less than 150 μm in diameter. An aqueous solution of phenolic hydroxyl derivative of carboxymethylcellulose (CMC-Ph) containing human hepatoma cell line (HepG2) cells and horse radish peroxidase (HRP) was injected into a coflowing stream of liquid paraffin, containing H2O2, resulting in cell-enclosing CMC-Ph microparticles, 135 μm in diameter, via a peroxidase-catalyzed crosslinking reaction. The CMC-Ph microparticles were then coated with a phenolic hydroxyl derivative of alginate (Alg-Ph) gel membrane several dozen micrometers in thickness, crosslinked via the same enzymatic reaction process, followed by further crosslinking between the carboxyl groups of alginate by Sr2+. A hollow core structure was achieved by immersing the resultant microcapsules in a medium containing cellulase, which degrades the enclosed CMC-Ph microparticles. The HepG2 cells in the microcapsules then grew and completely filled the hollow core. Multicellular spheroids the same size as the CMC-Ph microparticles, with living cells at their outer surface, were collected within 1 min by soaking them in a medium containing alginate lyase to degrade the Alg-Ph gel microcapsule membrane.

AB - Microcapsules with a single, spherical hollow core less than 150 μm in diameter were developed to obtain multicellular spheroids with well-defined sizes of less than 150 μm in diameter. An aqueous solution of phenolic hydroxyl derivative of carboxymethylcellulose (CMC-Ph) containing human hepatoma cell line (HepG2) cells and horse radish peroxidase (HRP) was injected into a coflowing stream of liquid paraffin, containing H2O2, resulting in cell-enclosing CMC-Ph microparticles, 135 μm in diameter, via a peroxidase-catalyzed crosslinking reaction. The CMC-Ph microparticles were then coated with a phenolic hydroxyl derivative of alginate (Alg-Ph) gel membrane several dozen micrometers in thickness, crosslinked via the same enzymatic reaction process, followed by further crosslinking between the carboxyl groups of alginate by Sr2+. A hollow core structure was achieved by immersing the resultant microcapsules in a medium containing cellulase, which degrades the enclosed CMC-Ph microparticles. The HepG2 cells in the microcapsules then grew and completely filled the hollow core. Multicellular spheroids the same size as the CMC-Ph microparticles, with living cells at their outer surface, were collected within 1 min by soaking them in a medium containing alginate lyase to degrade the Alg-Ph gel microcapsule membrane.

UR - http://www.scopus.com/inward/record.url?scp=69249209656&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69249209656&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2009.07.031

DO - 10.1016/j.biomaterials.2009.07.031

M3 - Article

C2 - 19656563

AN - SCOPUS:69249209656

VL - 30

SP - 5937

EP - 5942

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 30

ER -