Successive epoxy and carbodiimide cross-linking of dermal sheep collagen

• Published in: Biomaterials Vol. 20; no. 10; pp. 921 - 931
• Main Authors: Zeeman, Raymond, Dijkstra, Pieter J., van Wachem, Pauline B., van Luyn, Marja J.A., Hendriks, Marc, Cahalan, Patrick T., Feijen, Jan
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.05.1999; Elsevier Science
• Subjects: Acylation; Amines; Animals; Biocompatible Materials - chemistry; Biodegradation; Biological and medical sciences; Biomechanical Phenomena; Butylene Glycols; Carbodiimide; Collagen; Collagen - chemistry; Collagenases; Cross-linking; Cross-Linking Reagents; Crosslinking; Drug Stability; Enzyme kinetics; Epoxy compounds; Epoxy resins; Ethyldimethylaminopropyl Carbodiimide; In Vitro Techniques; In-vitro degradation; Materials Testing; Mechanical properties; Medical sciences; Polyimides; Pronase; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Sheep; Technology. Biomaterials. Equipments. Material. Instrumentation; Tensile Strength; Mechanical properties; Cross-linking; Collagen; Carbodiimide; In-vitro degradation; Epoxy compounds; Carboid; Epoxy resin; Crosslinking; In vitro; Imide; Vertebrata; Mammalia; Animal; Enzymatic digestion; Sheep; Biomaterial; Artiodactyla; Derm; Ungulata; Physicochemical properties
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/S0142-9612(98)00242-7

Cross-linking of dermal sheep collagen (N-DSC, T s=46°C, number of amine groups =31 (n/1000) ) with 1,4-butanediol diglycidyl ether (BDDGE) at pH 9.0 resulted in a material (BD90) with a high T s (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 T s 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 T s 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 T s to 62°C. The stability towards enzymatic degradation was reduced, but the tensile properties were comparable to BD45.