Experimental Gluing of Lung Parenchyma in Rats

Abstract

Gelatin-resorcinol-dialdehyde adhesive has been developed from a gelatin-resorcinol-formaldehyde adhesive by replacing the formaldehyde with two less histotoxic dialdehydes, ethandial and pentandial. The aim of the present study was to evaluate the usefulness of this modified composition in gluing defects in lung parenchyma. In 40 male Wistar rats a standardized lung incision 1.0 cm in length and 0.8 cm in depth were closed by application of gelatin-resorcinol-dialdehyde adhesive. For macroscopic and microscopic examination 4 animals were sacrificed on each of postoperative days 2, 7, and 14 and 14 animals on each of postoperative days 28 and 120. Macroscopic examination revealed a tight closure of the parenchymal defects in all postoperative stages. Initially by an adhesive layer and later on by granulation tissue and scar tissue respectively. On microscopic examination an inflammatory tissue response with polymorphonuclear neutrophils and macrophages predominating was found 2 days postoperatively. After 7 days multinucleated giant cells appeared. On postoperative day 14 the tissue response presented a distinct granulomatous character with multinucleated giant cells persisting. After 28 days remnants of adhesive surrounded by granulation tissue were detectable. On postoperative day 120 the adhesive had been completely resorbed and the parenchymal defect was replaced by fibrous scar tissue. The gelatin-resorcinol-adhesive proved effective in tight closure of lung parenchyma in rats. The adhesive is resorbed completely and does not interfere with parenchymal healing.

Tissue adhesives in ocular surgery

“…Concerns about formaldehyde's mutagenicity and carcinogenicity led Ennker and coinvestigators to replace the formaldehyde component of the glue and combine gelatin instead with less toxic aldehydes such as glutaraldehyde and glyoxal (gelatine-dialdehyde), pentanedial and ethanedial (GR-DIAL), and other CXL agents [158]. The gelatine-dialdehyde was tested on aortic tissue of pigs [159] and the GR-DIAL was tested on lung incisions in rabbits [160], as well as on lung parenchyma defects of rats [161]. These modified gelatin-based adhesives were reported to be resorbed in vivo without interfering with the healing process, and was shown to have no carcinogenic, mutagenic or toxic effects.…”

Crosslinking structures of gelatin hydrogels crosslinked with genipin or a water‐soluble carbodiimide

“…Although the bonding strength of the GRF glue to tissue was satisfactory, concerns about the cytotoxicity of formaldehyde were reported in the literature 6, 9. It was suggested that the cytotoxicity problem of the GRF glue could be overcome by a change in its crosslinking method 12. The feasibility of using a water‐soluble carbodiimide or genipin (GP) to crosslink a gelatin hydrogel for new bioadhesives was previously evaluated in vitro and in vivo by our group 13, 14…”

“…6,9 It was suggested that the cytotoxicity problem of the GRF glue could be overcome by a change in its crosslinking method. 12 The feasibility of using a water-soluble carbodiimide or genipin (GP) to crosslink a gelatin hydrogel for new bioadhesives was previously evaluated in vitro and in vivo by our group. 13,14 The results obtained in the in vitro study indicated that the cytotoxicity of the carbodiimide-and GP-crosslinked glues were significantly lower than that of the GRF glue.…”

Gelatin-derived bioadhesives for closing skin wounds: An in vivo study

“…Widespread acceptance of GRF glue, however, has been limited by reports of cytotoxicity due to its release of formaldehyde upon degradation [6,9]. It has been suggested that the cytotoxicity problem of the GRF glue may be overcome by changing its cross-linking method [12]. Several crosslinking agents including epoxy compounds [13,14], carbodiimides [1,2,15], and genipin [16,17] have recently been used to cross-link collagen-based biomaterials.…”