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Int. J. Mol. Sci. 2015, 16(6), 14143-14157; doi:10.3390/ijms160614143

Local Controlled Release of Polyphenol Conjugated with Gelatin Facilitates Bone Formation

1
Institute of Dental Research, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan
2
Graduate School of Science and Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
3
Department of Orthodontics, Osaka Dental University, 8-1, Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan
4
Department of Oral Implantology, Osaka Dental University; 8-1 Kuzuhahanazonocho, Hirakata, Osaka, 573-1121, Japan
5
Osaka Dental University; 8-1 Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan
6
Department of Oral Radiology, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Paula Andrade
Received: 20 April 2015 / Revised: 28 May 2015 / Accepted: 8 June 2015 / Published: 23 June 2015
(This article belongs to the Special Issue Phenolics and Polyphenolics 2015)
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Abstract

Catechins are extensively used in health care treatments. Nevertheless, there is scarce information about the feasibility of local administration with polyphenols for bone regeneration therapy, possibly due to lack of effective delivery systems. Here we demonstrated that the epigallocatechin-3-gallate-conjugated gelatin (EGCG/Gel) prepared by an aqueous chemical synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-morpholinium chloride (DMT-MM) gradually disintegrated with time and facilitated bone formation in a critical size defect of a mouse calvaria. Conjugation of EGCG with the Gel generated cross-linking between the two molecules, thereby leading to a retardation of the degradation of the EGCG/Gel and to a delayed release of EGCG. The prepared EGCG/Gels represented significant osteogenic capability compared with that of the uncross-linked Gel and the cross-linked Gel with uncombined-EGCG. In vitro experiments disclosed that the EGCG/Gel induced osteoblastogenesis of a mouse mesenchymal stem cell line (D1 cells) within 14 days. Using fluorescently-labeled EGCG/Gel, we found that the fraction of EGCG/Gel adsorbed onto the cell membrane of the D1 cells possibly via a Gel-cell interaction. The interaction might confer the long-term effects of EGCG on the cells, resulting in a potent osteogenic capability of the EGCG/Gel in vivo. These results should provide insight into local controlled release of polyphenols for bone therapy. View Full-Text
Keywords: catechin; EGCG; bone formation; gelatin; mesenchymal stem cells catechin; EGCG; bone formation; gelatin; mesenchymal stem cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Honda, Y.; Tanaka, T.; Tokuda, T.; Kashiwagi, T.; Kaida, K.; Hieda, A.; Umezaki, Y.; Hashimoto, Y.; Imai, K.; Matsumoto, N.; Baba, S.; Shimizutani, K. Local Controlled Release of Polyphenol Conjugated with Gelatin Facilitates Bone Formation. Int. J. Mol. Sci. 2015, 16, 14143-14157.

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