Cross-linking and modification of dermal sheep collagen using 1,4-butanediol diglycidyl ether

R. Zeeman, Pieter J. Dijkstra, P.B. van Wachem, M.J.A. van Luyn, M. Hendriks, P.T. Cahalan, Jan Feijen

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Crosslinking of dermal sheep collagen (DSC) was accomplished using 1,4-butanediol diglycidyl ether (BDDGE). At pH values > 8.0, epoxide groups of BDDGE will react with amine groups of collagen. The effects of BDDGE concentration, pH, time, and temperature were studied. Utilization of a 4-wt % BDDGE instead of 1-wt % resulted in a faster reaction. Whereas similar values of shrinkage temperature were obtained, fewer primary amine groups had reacted at a lower BDDGE concentration, which implies that the crosslinking reaction had a higher efficacy. An increase in pH from 8.5 to 10.5 resulted in a faster reaction but reduced crosslink efficacy. Furthermore, an increase in reaction temperature accelerated the reaction without changing the crosslink efficacy. Crosslinking under acidic conditions (pH < 6.0) evoked a reaction between epoxide groups and carboxylic acid groups of collagen. Additional studies showed that no oligomeric crosslinks could be formed. However, hydrolysis of the epoxide groups played a role in the crosslink mechanism especially under acidic reaction conditions. The macroscopic properties of these materials were dependent on the crosslinking method. Whereas a flexible and soft tissue was found if crosslinking was performed at pH < 6.0, a stiff sponge was obtained under alkaline conditions. Reaction of DSC with a monofunctional compound (glycidyl isopropyl ether) led to comparable trends in reaction rate and in similar macroscopical differences in materials as observed with BDDGE.
Original languageEnglish
Pages (from-to)424-433
JournalJournal of biomedical materials research
Issue number3
Publication statusPublished - 1999


  • Cross-linking
  • Collagen
  • Crosslinking efficacy
  • Kinetics
  • Epoxy compounds


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