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.
Highlights
Drug delivery systems (DDS) to convey drugs to specific sites are recognized as a prospective method to solve the limitation of conventional and systematic therapies, such as low drug efficacy, poor bioavailability, biodistribution, drug overdose, and toxicity [1,2]
EGCG/Gels were prepared by an aqueous synthesis using various amounts of a water-soluble dehydrative condensing agent, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride (DMT-MM), and N-methylmorpholine (NMM) (Figure 1 and Table 1)
The aqueous solution of the Gel, EGCG, DMT-MM, and NMM was stirred for 24 h at room temperature in the dark
Summary
Drug delivery systems (DDS) to convey drugs to specific sites are recognized as a prospective method to solve the limitation of conventional and systematic therapies, such as low drug efficacy, poor bioavailability, biodistribution, drug overdose, and toxicity [1,2]. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea catechin, has attracted significant attention as a health-promoting agent. This polyphenol is known to modulate multiple signaling pathways, including ERK [9], JNK [10,11], MEK1/2 [10], STAT 3 [10,12], and PI3K/Akt [9,10,13], and to cause cellular responses, including (a) cell proliferation [14]; (b) cell differentiation [13,14,15]; (c) cytokine production [11,12]; and (d) cell survival [9]. EGCG has been combined with artificial [21,22] and natural polymers [23,24]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
