Successive epoxy and carbodiimide cross-linking of dermal sheep collagen

R. Zeeman, Pieter J. Dijkstra, Pauline B. van Wachem, Marja J.A. van Luyn, Marc Hendriks, Patrick T. Cahalan, Jan Feijen

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Cross-linking of dermal sheep collagen (N-DSC, Ts=46°C, numberofaminegroups=31 (n/1000)) with 1,4-butanediol diglycidyl ether (BDDGE) at pH 9.0 resulted in a material (BD90) with a high Ts (69°C), a decreased number of amine groups of 15 (n/1000) and a high resistance towards collagenase and pronase degradation. Reaction of DSC with BDDGE at pH 4.5 yielded a material (BD45) with a Ts of 64°C, hardly any reduction in amine groups and a lower stability towards enzymatic degradation as compared to BD90. The tensile strength of BD45 (9.2 MPa) was substantially improved as compared to N-DSC (2.4 MPa), whereas the elongation at break was reduced from 210 to 140%. BD90 had a tensile strength of 2.6 MPa and an elongation at break of only 93%. To improve the resistance to enzymes and to retain the favorable tensile properties, BD45 was post-treated with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) in the presence of N-hydroxysuccinimide (NHS) to give BD45EN. Additional cross-linking via the formation of amide bonds took place as indicated by the Ts of 81°C and the residual number of amine groups of 19 (n/1000). BD45EN was stable during exposure to both collagenase and pronase solutions. The tensile properties (tensile strength 7.2 MPa, elongation at break 100%) were comparable to those of BD45 and glutaraldehyde treated controls (G-DSC). Acylation of the residual amine groups of BD45 with acetic acid N-hydroxysuccinimide ester (HAc-NHS) yielded BD45HAc with a large reduction in amine groups to 10 (n/1000) and a small reduction in Ts to 62°C. The stability towards enzymatic degradation was reduced, but the tensile properties were comparable to BD45.
Original languageUndefined
Pages (from-to)921-931
Issue number10
Publication statusPublished - 1999


  • METIS-105671
  • IR-74003
  • Mechanical properties
  • In vitro degradation
  • Cross-linking
  • Collagen
  • Carbodiimide
  • Epoxy compounds

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