Preparation of cross-linked hyaluronic acid film using 2-chloro-1-methylpyridinium iodide or water-soluble 1-ethyl-(3,3-dimethylaminopropyl)carbodiimide

Jenn Jong Young, Kuang Ming Cheng, Tai Li Tsou, Hwan Wun Liu, Hsian-Jenn Wang

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

In order to obtain much slower biodegradable films, which are often required for biomedical applications, we have developed a series of studies on heterogeneous cross-linking of hyaluronic acid (HA) films by using 2-chloro-1-methylpyridinium iodide (CMPI) or 1-ethyl-(3,3-dimethylaminopropyl)carbodiimide (EDC) as cross-linking reagents. From the in vitro degradation rate, we found that EDC cross-linked HA films completely dissolved in PBS at 37°C during the period of 4-6 days. However, CMPI cross-linked HA films showed only a low percentage of weight loss over 30 days. This phenomenon could be explained from the mechanism of reaction between carboxyl group of HA and EDC. The latter reacted with carboxyl group to form an unstable intermediate O-acylurea, which showed a relatively low reactivity and quickly rearranged to form a stable N-acylurea. Thus, most of the EDC-activated carboxyl groups in HA were chemically transferred into N-acylurea or left as unreactive O-acylurea, and only a few of cross-linking bonds were formed between HA. On the other hand, the intermediate obtained from the reaction between carboxyl group and CMPI showed a relatively high reactivity and reacted with the hydroxyl group of the same and/or different molecules of HA to form an inter- and intramolecular esterification. Apparently, CMPI cross-linked HA films have a much higher cross-linking density and constructed a more rigid three-dimensional network. Therefore, it produced HA films, which dramatically increased its enzymatic stability in aqueous solution of hyaluronidase. The obtained results from elemental analyses, FT-IR spectra and NMR spectra also indicate that acylurea groups were introduced into EDC-cross-linked HA films.

Original languageEnglish
Pages (from-to)767-780
Number of pages14
JournalJournal of Biomaterials Science, Polymer Edition
Volume15
Issue number6
DOIs
Publication statusPublished - Jul 27 2004
Externally publishedYes

Fingerprint

Ethyldimethylaminopropyl Carbodiimide
Hyaluronic acid
Hyaluronic Acid
Water
1-methylpyridinium
2-chloro-1-methylpyridinium
Cross-Linking Reagents
Hyaluronoglucosaminidase
Esterification
Hydroxyl Radical
Weight Loss

Keywords

  • 1-ethyl-(3,3-dimethylaminopropyl)carbodiimide
  • 2-chloro-1-methylpyridinium iodide
  • Biodegradation
  • Heterogeneous cross-linking
  • Hyaluronic acid

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biomedical Engineering

Cite this

Preparation of cross-linked hyaluronic acid film using 2-chloro-1-methylpyridinium iodide or water-soluble 1-ethyl-(3,3-dimethylaminopropyl)carbodiimide. / Young, Jenn Jong; Cheng, Kuang Ming; Tsou, Tai Li; Liu, Hwan Wun; Wang, Hsian-Jenn.

In: Journal of Biomaterials Science, Polymer Edition, Vol. 15, No. 6, 27.07.2004, p. 767-780.

Research output: Contribution to journalArticle

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T1 - Preparation of cross-linked hyaluronic acid film using 2-chloro-1-methylpyridinium iodide or water-soluble 1-ethyl-(3,3-dimethylaminopropyl)carbodiimide

AU - Young, Jenn Jong

AU - Cheng, Kuang Ming

AU - Tsou, Tai Li

AU - Liu, Hwan Wun

AU - Wang, Hsian-Jenn

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