Biological effects of residual glutaraldehyde in glutaraldehyde‐tanned collagen biomaterials

TLDR

Glutaraldehyde is widely used to crosslink collagen, reducing its solubility, antigenicity, and biodegradation, while adverse reactions are mainly limited to contact dermatitis and biocidal effects. This study examined how residual glutaraldehyde in a tanned collagen sponge correlates with cytotoxicity to fibroblasts and foreign‑body giant cell responses. Fibroblast proliferation was 99 % inhibited at 3 ppm glutaraldehyde, and sponge extracts released 6 µg g⁻¹ at pH 7 and 65 µg g⁻¹ at pH 4.5—tenfold higher—indicating leaching sufficient to provoke adverse cellular effects in vitro and in vivo.

Abstract

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 μg and 65 μg 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 .