In situ formation and collagen-alginate composite encapsulation of pancreatic islet spheroids

Bo Ram Lee, Jin Wook Hwang, Yoon Young Choi, Sau Fung Wong, Yong Hwa Hwang, Dong Yun Lee, Sang Hoon Lee

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

In this study, we suggest in situ islet spheroid formation and encapsulation on a single platform without replating as a method for producing mono-disperse spheroids and minimizing damage to spheroids during encapsulation. Using this approach, the size of spheroid can be controlled by modulating the size of the concave well. Here, we used 300 μm concave wells to reduce spheroid size and thereby eliminating the central necrosis caused by large volume. As the encapsulation material, we used alginate and collagen-alginate composite (CAC), and evaluated their suitability through diverse in vitro tests, including measurements of viability, oxygen consumption rate (OCR), hypoxic damage to encapsulated spheroids, and insulin secretion. For in situ encapsulation, alginate or CAC was spread over a concave microwell array containing spheroids, and CaCl 2 solution was diffused through a nano-porous dialysis membrane to achieve uniform polymerization, forming convex structures. By this process, the formation of uniform-size islet spheroids and their encapsulation without an intervening replating step was successfully performed. As a control, intact islets were evaluated concurrently. The in vitro test demonstrated excellent performance of CAC-encapsulated spheroids, and on the basis of these results, we transplanted the islet spheroids-encapsulated with CAC into the intraperitoneal cavity of mice with induced diabetes for 4 weeks, and evaluated subsequent glucose control. Intact islets were also transplanted as control to investigate the effect of encapsulation. Transplanted CAC-encapsulated islet spheroids maintained glucose levels below 200 mg/dL for 4 weeks, at which they were still active. At the end of the implantation experiment, we carried out intraperitoneal glucose tolerance test (IPGTT) in mice to investigate whether the implanted islets remained responsive to glucose. The glucose level in mice with CAC-encapsulated islet spheroids dropped below 200 mg/dL 60 min after glucose injection and was stably maintained. In conclusion, the proposed encapsulation method enhances the viability and function of islet spheroids, and protects these spheroids from immune attack.

Original languageEnglish
Pages (from-to)837-845
Number of pages9
JournalBiomaterials
Volume33
Issue number3
DOIs
Publication statusPublished - 2012 Jan 1

Fingerprint

Alginate
Islets of Langerhans
Encapsulation
Collagen
Glucose
Composite materials
Dialysis membranes
alginic acid
Insulin
Glucose Tolerance Test
Medical problems
Oxygen Consumption
Polymerization
Dialysis
Necrosis
Oxygen
Injections
Membranes

Keywords

  • Collagen-alginate composite (CAC) encapsulation
  • Concave microwell array
  • Glucose control
  • Islet spheroids
  • Type-1 diabetes mellitus (T1DM)
  • Xenogenic transplantation

ASJC Scopus subject areas

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

Cite this

In situ formation and collagen-alginate composite encapsulation of pancreatic islet spheroids. / Lee, Bo Ram; Hwang, Jin Wook; Choi, Yoon Young; Wong, Sau Fung; Hwang, Yong Hwa; Lee, Dong Yun; Lee, Sang Hoon.

In: Biomaterials, Vol. 33, No. 3, 01.01.2012, p. 837-845.

Research output: Contribution to journalArticle

Lee, Bo Ram ; Hwang, Jin Wook ; Choi, Yoon Young ; Wong, Sau Fung ; Hwang, Yong Hwa ; Lee, Dong Yun ; Lee, Sang Hoon. / In situ formation and collagen-alginate composite encapsulation of pancreatic islet spheroids. In: Biomaterials. 2012 ; Vol. 33, No. 3. pp. 837-845.
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