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  • Improving alginate-poly-L-ornithine-alginate capsule biocompatibility through genipin crosslinking.

Improving alginate-poly-L-ornithine-alginate capsule biocompatibility through genipin crosslinking.

Journal of biomedical materials research. Part B, Applied biomaterials (2012-11-21)
Anna L Hillberg, Kalyani Kathirgamanathan, Janice B B Lam, Lee Yong Law, Olga Garkavenko, Robert B Elliott
ABSTRACT

DIABECELL® capsules comprise an inner core of alginate (Alg) coated with a polycationic polymer, poly-L-ornithine (PLO), designed as a stabilizing agent for strengthening the capsule wall, which is masked by an outer layer of biocompatible Alg. These polymeric microcapsules have demonstrated excellent mechanical properties and a reduction in hypoglycemia after tranplantation in human clinical trials; however, degradation of the outer Alg layer leaves the underlying layers of PLO exposed, which ultimately leads to reduced biocompatibility in vivo. Here we aim to improve capsule biocompatibility and to increase the hydrophilic properties of the capsule surface through chemical crosslinking/modification of the PLO layer using genipin. Fluorescence microscopy established crosslinking was limited to the layers of PLO. In vitro experiments confirmed islet viability and insulin release within chemically modified capsules over the course of a month and in vivo investigations demonstrated improved biocompatibility when comparing standard Alg/PLO/Alg capsules with genipin modified capsules.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Poly-L-ornithine solution, mol wt 30,000-70,000, 0.01%, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Genipin, ≥98% (HPLC), powder
Sigma-Aldrich
Poly-L-ornithine hydrobromide, mol wt 30,000-70,000
Sigma-Aldrich
Poly-L-ornithine hydrobromide, mol wt 5,000-15,000
Sigma-Aldrich
Poly-L-ornithine hydrobromide, mol wt >100,000