Abstract:Bioadhesives have been used in surgery as hemostatic and wound healing agents. GRF (gelatin + resorcinol + formaldehyde) glue, composed of a mixture of gelatin and resorcinol polymerized by the addition of formaldehyde, has been used for this purpose. Widespread acceptance of the GRF glue, however, has been limited by reports of cytotoxicity due to its release of formaldehyde upon degradation. It has been suggested by Wertzel et al. that the cytotoxicity problem of GRF glue may be overcome by changing its cros… Show more
“…The in vitro and in vivo toxicity of crosslinked genipin has been reported to be minimal and significantly lower than the toxic level of more popular crosslinkers, such as glutaraldehyde [23][24][25][26]. These reports are consistent with our in vitro cytotoxicity study, as media extracted from BSAgenipin solders that underwent thermal treatment did not inhibit significantly the growth of murine fibroblasts.…”
Addition of a chemical crosslinking agent, such as genipin, significantly increased the tensile strength of adhesive-tissue bonds. A proposed mechanism for this enhanced bond strength is the synergistic action of mechanical adhesion with chemical crosslinking by genipin.
“…The in vitro and in vivo toxicity of crosslinked genipin has been reported to be minimal and significantly lower than the toxic level of more popular crosslinkers, such as glutaraldehyde [23][24][25][26]. These reports are consistent with our in vitro cytotoxicity study, as media extracted from BSAgenipin solders that underwent thermal treatment did not inhibit significantly the growth of murine fibroblasts.…”
Addition of a chemical crosslinking agent, such as genipin, significantly increased the tensile strength of adhesive-tissue bonds. A proposed mechanism for this enhanced bond strength is the synergistic action of mechanical adhesion with chemical crosslinking by genipin.
“…Gelatin, which is essentially denatured collagen, has a myriad of uses in the food, pharmaceutical and cosmetic industries [9]. As for the genipin, it is a naturally occurring and low-cytotoxic crossing agent, which can be obtained from its parent compound geniposide isolated from the fruits of Gardenia jasminoides ELLIS [10,11]. In the present study, we describe the synthesis of the genipin-cross-linked gelatin conduit (GGC).…”
“…17 The feasibility of using genipin to crosslink gelatin as a novel biological glue to close skin-wound lesions has been previously evaluated in vitro and in vivo in a rat model. 18,19 Formaldehyde and glutaraldehyde were used as controls. The results showed that the cytotoxicity of the genipin-crosslinked glue was significantly less than the aldehyde-crosslinked glues.…”
Gelatin microspheres have been widely evaluated as a drug carrier. Nevertheless, gelatin dissolves rather rapidly in aqueous environments, making the use of the polymer difficult for the production of long-term delivery systems. This adverse aspect requires the use of a crosslinking agent in forming nonsoluble networks in microspheres. However, the use of crosslinking agents such as formaldehyde and glutaraldehyde can lead to toxic side effects owing to residual crosslinkers. In an attempt to overcome this problem, a naturally occurring crosslinking agent (genipin) was used to crosslink gelatin microspheres as a biodegradable drug-delivery system for intramuscular administration. Glutaraldehyde was used as a control. In the in vitro study, the morphology, dynamic swelling, and antienzymatic degradation of test microspheres were evaluated. In the in vivo study, the biocompatibility and degradability of test microspheres were implanted in the skeletal muscle of a rat model via intramuscular injection. The results obtained in the study suggested that crosslinking of gelatin microspheres with glutaraldehyde or genipin may produce distinct crosslinking structures. The water transport mechanism in both the glutaraldehyde- and genipin-crosslinked gelatin microspheres exhibit anomalous behavior ranging from Fickian to Case-II extremes. The increase of the swelling diameter for the genipin-crosslinked microspheres was significantly less than that observed for the glutaraldehyde-crosslinked microspheres. In the animal study, it was found that the degree in inflammatory reaction for tissues implanted with the genipin-crosslinked microspheres was significantly less than that implanted with the glutaraldehyde-crosslinked microspheres. Additionally, the degradation rate of the genipin-crosslinked microspheres was significantly slower than their glutaraldehyde-crosslinked counterparts. These results indicated that the genipin-crosslinked gelatin microspheres may be used as a long-acting drug carrier for intramuscular administration.
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