Gelatin has been frequently used in tissue engineering scaffold due to its favorable biological properties in wound healing enhancement. Genipin, a natural compound derived from Gardenia plants, was shown to be effective in improving physicochemical characteristics of the gelatin scaffold. This systematic review reported the utility of genipin as a crosslinker in gelatin scaffold fabrication. Two electronic databases, namely Scopus and MEDLINE via Ebcoshost were searched for publication between January 1999 and December 2018, using the keywords ‘gelatin’ and ‘genipin’. Articles published in English, reporting the utility of genipin in the fabrication of gelatin sponge were included. The keywords search yielded 830 articles, in which 14 articles were selected and examined in this review. The result of the search provided input in terms of the optimum concentration, crosslinking temperature, and fabrication method of genipin to be used. From the literature, it was found that 0.5% is the optimum genipin concentration and 25˚C is the optimum crosslinking temperature. The result also revealed a gap in the knowledge regarding genipin crosslinker and justifies the need to create awareness of the utility of genipin as a gelatin scaffold crosslinker. The current review provides an extensive overview on the current knowledge on genipin crosslinking and be a guide to an optimal fabrication of the genipin-crosslinked gelatin scaffold.
The full-thickness skin wound is a common skin complication affecting millions of people worldwide. Delayed treatment of this condition causes the loss of skin function and integrity that could lead to the development of chronic wounds or even death. This study was aimed to develop a rapid wound treatment modality using ovine tendon collagen type I (OTC-I) bio-scaffold with or without noncultured skin cells. Genipin (GNP) and carbodiimide (EDC) were used to cross-link OTC-I scaffold to improve the mechanical strength of the bio-scaffold. The physicochemical, biomechanical, biodegradation, biocompatibility, and immunogenicity properties of OTC-I scaffolds were investigated. The efficacy of this treatment approach was evaluated in an in vivo skin wound model. The results demonstrated that GNP cross-linked OTC-I scaffold (OTC-I_GNP) had better physicochemical and mechanical properties compared with EDC cross-linked OTC-I scaffold (OTC-I_EDC) and noncross-link OTC-I scaffold (OTC-I_NC). OTC-I_GNP and OTC-I_NC demonstrated no toxic effect on cells as it promoted higher cell attachment and proliferation of both primary human epidermal keratinocytes and human dermal fibroblasts compared with OTC-I_EDC. Both OTC-I_GNP and OTC-I_NC exhibited spontaneous formation of bilayer structure in vitro. Immunogenic evaluation of OTC-I scaffolds, in vitro and in vivo, revealed no sign of immune response. Finally, implantation of OTC-I_NC and OTC-I_GNP scaffolds with noncultured skin cells demonstrated enhanced healing with superior skin maturity and microstructure features, resembling native skin in contrast to other treatment (without noncultured skin cells) and control group. The findings of this study, therefore, suggested that both OTC-I scaffolds with noncultured skin cells could be promising for the rapid treatment of full-thickness skin wound.