Abstract
Matrix metalloproteinase (MMP)-2 and MMP-9 are well-known gelatinases that disrupt the extracellular matrix, including gelatin. However, the advantages of modulating MMP expression in gelatin-based materials for applications in bone regenerative medicine have not been fully clarified. In this study, we examined the effects of epigallocatechin gallate (EGCG), a major polyphenol catechin isolated from green tea, on MMP expression in gelatin sponges and its association with bone formation. Four gelatin sponges with or without EGCG were prepared and implanted into bone defects for up to 4 weeks. Histological and immunohistological staining were performed. Micro-computed tomography was used to estimate the bone-forming capacity of each sponge. Our results showed that EGCG integration attenuated MMP-2 (70.6%) and -9 expression (69.1%) in the 1 week group, increased residual gelatin (118.7%), and augmented bone formation (101.8%) in the 4 weeks group in critical-sized bone defects of rat calvaria compared with vacuum-heated gelatin sponges without EGCG. Moreover, vacuum-heated gelatin sponges with EGCG showed superior bone formation compared with other sponges. The results indicated that integration of EGCG in gelatin-based materials modulated the production and activity of MMP-2 and -9 in vivo, thereby enhancing bone-forming capacity.
Highlights
Treatment of bone defects has been extensively studied in dentistry, orthopedic surgery, and plastic surgery to heal trauma, inflammation, and congenital diseases [1,2,3]
In the current study, we showed that the presence of chemically modified epigallocatechin gallate (EGCG) in gelatin markedly reduced Matrix metalloproteinase (MMP)-2, MMP-9, and 4-HNE levels in defects compared with that in samples treated with gelatin without EGCG
We could not identify the exact concentrations of MMP-2 and -9 at the site of bone defects in vivo, our results revealed that chemical modification of EGCG on gelatin delayed the degradation of gelatin on vhEGCG-gelatin sponge (GS) in the presence of MMP-2 in vitro
Summary
Treatment of bone defects has been extensively studied in dentistry, orthopedic surgery, and plastic surgery to heal trauma, inflammation, and congenital diseases [1,2,3]. Various studies have aimed to limit the degradability of gelatin using chemical and physical crosslinking, such as genipin, glutaraldehyde, ultraviolet irradiation, and dehydrothermal treatment [5,7,11,12]. These crosslinking methods attenuate the degradability of gelatin, further improvements are needed to increase the bone-forming capacity of gelatin-based scaffolds comparable with autogenous bone grafts
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