Effect of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide concentrations on the mechanical and biological characteristics of cross-linked collagen fibres for tendon repair

Abstract

Reconstituted type I collagen fibres have received considerable interest as tendon implant materials due to their chemical and structural similarity to the native tissue. Fibres produced through a semi-continuous extrusion process were cross-linked with different concentrations of the zero-length cross-linker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) in combination with N-hydroxysuccinimide (NHS). Tensile properties of the fibres were considered, along with imaging of both surface structure and fibrillar alignment. Resistance of the fibres to bacterial collagenase was investigated and fibre sections seeded with human tendon cells for biological characterization, including cell adhesion and proliferation. The work clearly demonstrated that whilst the concentration of EDC and NHS had no significant effect on the mechanics, a higher concentration was associated with higher collagenase resistance, but also provided a less attractive surface for cell adhesion and proliferation. A lower cross-linking concentration offered a more biocompatible material without reduction in mechanics and with a potentially more optimal degradability.

Interleukin-6 Neutralization by Antibodies Immobilized at the Surface of Polymeric Nanoparticles as a Therapeutic Strategy for Arthritic Diseases

“…Indeed, several works have being demonstrated the in vitro and in vivo cytocompatibility of EDC/NHS chemistry. 33 Stable NPs with 121.8 ± 2.4 nm of diameter, 0.11 ± 0.01 of PDI, and +25.12 ± 1.86 mV of zeta potential were produced with 0.25 mg/mL of concentration of the initial polymers solutions, at pH 5, and with 50/200 mM of EDC/NHS concentration, after their centrifugation with glucose. NPs size and PDI significantly increased without the addition of this sugar to the NPs suspension.…”

Collagen: a network for regenerative medicine

“…98 Cellular proliferation is also affected negatively by cross-linking protocols which maximize mechanical strength. 109,112 On collagen fibers, increases in mechanical strength, as EDC concentration ranges from 0.25 to 25 mM, significantly decrease cell proliferation. 109 The same was shown to occur in collagen scaffolds.…”

“…109,112 On collagen fibers, increases in mechanical strength, as EDC concentration ranges from 0.25 to 25 mM, significantly decrease cell proliferation. 109 The same was shown to occur in collagen scaffolds. As EDC concentration was increased from 6 mM to 96 mM, cell proliferation became negligible.…”

“…It has been shown, for example, that cross-linkers which interfere with integrin ligands cause significant decreases in cell attachment, proliferation and migration. 98,109–111 In general, as the cross-linking strength increases, the cellular response becomes less favorable, even in the absence of cytotoxic effects due to the cross-linker itself. At EDC cross-linking strengths of less than 10% what is normally used in literature, the attachment of HT1080 cells increased by 5 times, and the scaffolds remained stable in physiological conditions.…”

An improved synthesis of a cyclopropene-based molecule for the fabrication of bioengineered tissues via copper-free click chemistry

“…[5][6][7] However, such chemical groups can negatively affect the biodegradation rate and cytotoxicity of the polymer. The synthetic protocols required to introduce these chemical groups can also generate toxic byproducts, 8,9 hampering translation, large-scale synthesis, and commercialization of such biomaterials into the clinical market.…”