Characterization and biocompatibility of epoxy-crosslinked dermal sheep collagens

Abstract

Dermal sheep collagen (DSC), which was crosslinked with 1, 4-butanediol diglycidyl ether (BD) by using four different conditions, was characterized and its biocompatibility was evaluated after subcutaneous implantation in rats. Crosslinking at pH 9.0 (BD90) or with successive epoxy and carbodiimide steps (BD45EN) resulted in a large increase in the shrinkage temperature (T(s)) in combination with a clear reduction in amines. Crosslinking at pH 4.5 (BD45) increased the T(s) of the material but hardly reduced the number of amines. Acylation (BD45HAc) showed the largest reduction in amines in combination with the lowest T(s). An evaluation of the implants showed that BD45, BD90, and BD45EN were biocompatible. A high influx of polymorphonuclear cells and macrophages was observed for BD45HAc, but this subsided at day 5. At week 6 the BD45 had completely degraded and BD45HAc was remarkably reduced in size, while BD45EN showed a clear size reduction of the outer DSC bundles; BD90 showed none of these features. This agreed with the observed degree of macrophage accumulation and giant cell formation. None of the materials calcified. For the purpose of soft tissue replacement, BD90 was defined as the material of choice because it combined biocompatibility, low cellular ingrowth, low biodegradation, and the absence of calcification with fibroblast ingrowth and new collagen formation.

Influence of different collagen species on physico-chemical properties of crosslinked collagen matrices

“…The high enzymatic turnover rate of natural collagen in vivo makes stabilization of collagen-based biomaterials necessary. This can be achieved by chemical crosslinking methods, which provide biomaterials with desired mechanical properties for implantation and defect repair [23][24][25]. Several chemical agents have been used to achieve this goal.…”

“…The physicochemical and biological properties after crosslinking have been described extensively [29,[33][34][35]. For EDC/NHS-crosslinking, collagen of bovine [20,25,31,32,[36][37][38], ovine [24,28,[39][40][41] or porcine [30,42] origin has been used.…”

Dimethyl 3,3?-dithiobispropionimidate: A novel crosslinking reagent for collagen

“…However, toxicity and long-term calcification are major drawbacks of collagen crosslinked with GTA. [9][10][11] Several reagents have been tried as alternatives for crosslinking of collagen. 12,13 We evaluated the use of dimethyl suberimidate (DMS), a diimidoester, comparing it with GTA as a crosslinking agent for collagen.…”

Biodegradable organic acid-crosslinked alkali-treated gelatins with anti-thrombogenic and endothelialization properties

“…However, gelatin is rarely used in clinical applications, because aqueous gelatin solutions have a sol-gel transition point around human body temperature. Various chemical crosslinkers, such as glutaraldehyde [11,12], carbodiimide [13] and epoxy [14] problem. However, gelatin hydrogels prepared using these chemicals are cytotoxic and induce chronic inflammation.…”