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J Biomed Mater Res A. 2009 Jun 15;89(4):895-908. doi: 10.1002/jbm.a.32031.

Cross-linking of extruded collagen fibers--a biomimetic three-dimensional scaffold for tissue engineering applications.

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Tissue Modulation Laboratory, National University of Singapore, 117510, Singapore.


The repair of tissue defects remains a challenging clinical problem. Extruded collagen fibers comprise a promising scaffold for anterior cruciate ligament and tendon reconstruction; however the engineering of these fibers has still to be improved to bring this material to clinical practice. In this study, for the first time we investigated the influence of a wide range of cross-linking approaches (chemical, physical, and biological) on the properties of these fibers. Ultrastructural evaluation revealed a closely packed interfiber structure independent of the cross-linking method employed. The thermal properties were dependent on the cross-linking method employed and closely matched native tissues. The stress-strain curves were found to depend on the water content of the fibers, which was influenced by the cross-linking method. An inversely proportional relationship between both dry and wet fiber diameter and stress at break was found, which indicates that tailored-made biomaterials can be produced. Overall, the chemical stabilizations were more potent than both physical and biological approaches. Bifunctional agents such as hexamethylene diisocyanate and ethylene glycol diglycidyl ether or agents that promote matrix formation such as glutaraldehyde produced fibers with properties similar to those of native or synthetic fibers to suit a wide range of tissue engineering applications.

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