Abstract

Chemical modification of gelatin using epigallocatechin gallate (EGCG) promotes bone formation in vivo. However, further improvements are required to increase the mechanical strength and bone-forming ability of fabricated EGCG-modified gelatin sponges (EGCG-GS) for practical applications in regenerative therapy. In the present study, we investigated whether vacuum heating-induced dehydrothermal cross-linking of EGCG-GS enhances bone formation in critical-sized rat calvarial defects. The bone-forming ability of vacuum-heated EGCG-GS (vhEGCG-GS) and other sponges was evaluated by micro-computed tomography and histological staining. The degradation of sponges was assessed using protein assays, and cell morphology and proliferation were verified by scanning electron microscopy and immunostaining using osteoblastic UMR106 cells in vitro. Four weeks after the implantation of sponges, greater bone formation was detected for vhEGCG-GS than for EGCG-GS or vacuum-heated gelatin sponges (dehydrothermal cross-linked sponges without EGCG). In vitro experiments revealed that the relatively low degradability of vhEGCG-GS supports cell attachment, proliferation, and cell–cell communication on the matrix. These findings suggest that vacuum heating enhanced the bone forming ability of EGCG-GS, possibly via the dehydrothermal cross-linking of EGCG-GS, which provides a scaffold for cells, and by maintaining the pharmacological effect of EGCG.

Highlights

  • Cost is a major limitation for further progress in the field of regenerative therapy [1].The functionalization of cost-effective and abundant molecules is an attractive strategy to produce useful materials to overcome this issue

  • We developed a novel bone substitute material, i.e., vacuum-heated epigallocatechin gallate (EGCG)-modified gelatin sponges, for bone regenerative therapy

  • Our results demonstrate that vacuum heating enhances the bone-forming ability of EGCG-modified gelatin sponges (EGCG-gelatin sponge (GS))

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Summary

Introduction

Cost is a major limitation for further progress in the field of regenerative therapy [1].The functionalization of cost-effective and abundant molecules is an attractive strategy to produce useful materials to overcome this issue. Green and oolong teas contain a variety of polyphenol catechins, such as epicatechin, epigallocatechin gallate (EGCG), and gallocatechin gallate (GCG) [3,4]. EGCG, the most abundant catechin in green tea, has greater pharmacological effects than those of other catechins [5]. The safety [2] and cost-effectiveness [10] of EGCG support its broad medical usage. EGCG is already recognized as a prospective health-promoting agent in various medical fields, with applications in diabetes [11], Alzheimer’s disease [12], obesity [13], cardiovascular disease [14], cancer [3,15], bone disease [16], and oral disease [17]

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