Biological effects of residual glutaraldehyde in glutaraldehyde‐tanned collagen biomaterials

Abstract

Glutaraldehyde is commonly used to control physical and biological properties of collagen structure by means of intramolecular and/or intermolecular crosslinking of collagen molecules. Solubility, antigenicity, and biodegradation of naturally occurring or reconstituted collagenous matrices are effectively reduced by glutaraldehyde treatment. Adverse biological reactions to glutaraldehyde have been limited to infrequent contact dermatitis and to biocidal effects which are exploited in chemical sterilization media. In the present study of glutaraldehyde-tanned collagen sponge, the presence of glutaraldehyde was correlated with cytotoxic effects upon fibroblasts in tissue culture and foreign body giant cell reaction to bioimplants of the sponge. Fibroblast growth in tissue culture is 99% inhibited at media concentrations of 3.0 ppm glutaraldehyde. Extracts of glutaraldehyde collagen sponge in aqueous media at pH 7 and 4.5 yielded 6 micrograms and 65 micrograms glutaraldehyde per gram of collagen sponge, respectively. The yield increased tenfold at pH 4.5. Observations indicate that leaching of the glutaraldehyde from glutaraldehyde-tanned collagen sponge is sufficient to produce potentially adverse cellular effects both in vivo and in vitro.

Novel flower-shaped albumin particles as controlled-release carriers for drugs to penetrate the round-window membrane

“…These results indicated that FBSA-H had better cytocompatibility with no inherent cytotoxicity. The slight cytotoxicity of FBSA-GA was in agreement with that described in Speer et al 26 We also found an individual cell passing through the petal of FBSA ( Figure 6A, indicated by arrow). All of this suggested that FBSA might be a good scaffold for threedimensional cell culture, especially for tumor cells.…”

Cytocompatibility studies of mouse pancreatic islets on gelatin - PVP semi IPN scaffolds in vitro: Potential implication towards pancreatic tissue engineering

“…20 However during in vivo transplantation, GTA can be toxic due to the degradation of polymer. 20,21 Hence biocompatible water soluble carbodiimide class cross linker EDC has also been tried, which is widely used for cross linking collagen in dermal tissue engineering. 22 EDC crosslink the amino groups of one polypeptide chain with the carboxylic groups of the adjacent polypeptide chain by forming the extra amide bond without its incorporation.…”

Non‐enzymatic glycation of chondrocyte‐seeded collagen gels for cartilage tissue engineering

“…Although a number of crosslinkers have been used for increasing the mechanical properties of these gels, the majority of these agents are cytotoxic or may induce an immune response when constructs are implanted in vivo. [20][21][22] Non-enzymatic glycation, the crosslinking of proteins via reducing sugars, has been shown to change the mechanical properties of proteins both in vivo and in vitro, [23][24][25][26][27][28][29] and is a recognized method for in situ processing of cell-seeded tissue constructs. 23,30 This mechanism of crosslinking has been developed to process collagen gels both in their solid state and in solution.…”