Epigallocatechin-3-gallate Cross-Linked Small Intestinal Submucosa for Guided Bone Regeneration

Abstract

Collagen membranes are widely used in guided bone regeneration (GBR) because of their good biocompatibility and low immunogenicity. As a bioderived collagen membrane, small intestinal submucosa (SIS) has good regenerative potential for soft tissue repair, but it lacks sufficient mechanical properties for GBR application unless properly modifided. Epigallocatechin-3-gallate (EGCG) is a natural cross-linking agent featuring osteoinductive activity. In this study, we modified SIS by EGCG cross-linking, and such modified materials were characterized both in vitro and in vivo. The results showed that EGCG cross-linking significantly improved the mechanical properties and hydrophilicity of SIS while maintaing good cytocompatibility. Compared to SIS, EGCG-cross-linked SIS (E-SIS) enhanced the adhesion of fibroblasts and preosteoblasts and promoted the osteogenic differentiation of MC3T3-E1 cells cultured on the materials. In a rat cranial defect model, E-SIS material showed better occlusion effect than SIS material. Most importantly, E-SIS material accelerated bone regeneration more than SIS material and even a commercially available GBR membrane. Taken together, we conclude that E-SIS is a promising material as a GBR membrane.

Sustained Release of Catechin from Gelatin and Its Effect on Bone Formation in Critical Sized Defects in Rat Calvaria

“…4). Previous studies have reported that pore sizes below 50 μm in collagen sponges promote osteoconduction 21,33) . Given these results, although small pores of c.a.…”

“…Generally, the pore size is known to alter the bone-forming ability of materials 32) , and the optimal pore size of calcium phosphate-based materials for bone regeneration is recognized to be over 100 μm 32) . However, the adequate pore size of polymer-based sponges for bone regeneration remains unclear because the immersion of materials in body fluid causes swelling, thereby changing the pore size 21) . In fact, both NC-and AC-vhEGCG-GSs could induce bone formation in the center of defects (Fig.…”

“…Other studies have addressed the efficacy of the non-chemical modification technique using EGCG in combination with other biomaterials, including synthetic polymers 3,22) , alpha-tricalcium phosphate 34) , and collagen 35) for bone tissue engineering. Some studies showed that physical adsorption of EGCG on the other biomaterials without any chemical modification increased the capacity for bone formation 3,21,34) . Given these results, type A gelatin might enable the interaction, albeit weak, of EGCG with itself.…”

“…Consequently, numerous delivery systems have been developed to provide localized release of these therapeutic agents in biomedical engineering 17) . For EGCG, various techniques have been developed to retain or deliver EGCG in the affected areas; these techniques include chemical bonding to polymers 14,16,18) , layer by layer technique 19) , hydrophobic and/or hydrogen bonding 20,21) , EGCG-coating associated with Na + -mediated physical self-assembly 22) and oxidative polymerization 3) , and en-capsulation in drug carriers 23) . Although our understanding of the application of this molecule in bone regenerative therapy remains limited when compared with that in other medical fields, we previously found that gelatin sponges chemically modified with EGCG using an aqueous chemical synthesis method (hereafter designated as AC-EGCG-GS) induced superior bone formation in critical-sized bone defects (4.2 mm of diameter) in mouse calvaria 14) .…”

Procyanidins-crosslinked small intestine submucosa: A bladder patch promotes smooth muscle regeneration and bladder function restoration in a rabbit model

“…Known as a condensed tannin, PC consist of oligomer or polymers of (epi) catechin, whose phenolic hydroxyl structures have the capacity to form intermolecular hydrogen bonds. Unlike epigallocatechin gallate (EGCG), a catechin monomer with pro-osteogenesis activity [ 44 ], PC has anti-calcification activity which is favorable for bladder repair. In this study, PC was tested as a crosslinking agent for SIS membrane to generate a cell-free scaffold for their potential for bladder reconstruction.…”