Osteogenesis of Multipotent Progenitor Cells using the Epigallocatechin Gallate-Modified Gelatin Sponge Scaffold in the Rat Congenital Cleft-Jaw Model

Abstract

Cost-effective and functionalized scaffolds are in high demand for stem-cell-based regenerative medicine to treat refractory bone defects in craniofacial abnormalities and injuries. One potential strategy is to utilize pharmacological and cost-effective plant polyphenols and biocompatible proteins, such as gelatin. Nevertheless, the use of chemically modified proteins with plant polyphenols in this strategy has not been standardized. Here, we demonstrated that gelatin chemically modified with epigallocatechin gallate (EGCG), the major catechin isolated from green tea, can be a useful material to induce bone regeneration in a rat congenial cleft-jaw model in vivo when used with/without adipose-derived stem cells or dedifferentiated fat cells. Vacuum-heated gelatin sponges modified with EGCG (vhEGCG-GS) induced superior osteogenesis from these two cell types compared with vacuum-heated gelatin sponges (vhGS). The EGCG-modification converted the water wettability of vhGS to a hydrophilic property (contact angle: 110° to 3.8°) and the zeta potential to a negative surface charge; the modification enhanced the cell adhesion property and promoted calcium phosphate precipitation. These results suggest that the EGCG-modification with chemical synthesis can be a useful platform to modify the physicochemical property of gelatin. This alteration is likely to provide a preferable microenvironment for multipotent progenitor cells, inducing superior bone formation in vivo.

Integration of Epigallocatechin Gallate in Gelatin Sponges Attenuates Matrix Metalloproteinase-Dependent Degradation and Increases Bone Formation

“…The bone-forming capacity of vhEGCG-GS was found to be superior to that of vacuum-heated GS (vhGS). Combined use of vhEGCG-GS with multipotent progenitor cells, such as rat dedifferentiated fat cells and adipose-derived stem cells, resulted in greater bone-forming capacity than use of vhGS with both cells [29]. Based on these studies using vhEGCG-GS and vhGS, we hypothesized that postoperative modulation of MMP expression around the implanted materials may contribute to the bone-forming capacity of gelatin-based bone regenerative materials.…”

Comparison of Osteogenic Potentials of Dental Pulp and Bone Marrow Mesenchymal Stem Cells Using the New Cell Transplantation Platform, CellSaic, in a Rat Congenital Cleft-Jaw Model

“…In previous studies, many experiments have used rat bone defect models, such as those related to skull bones, jawbones, and long bones [14,[36][37][38][39], to evaluate the osteogenic ability of biomaterials. Most of these models relied on bone defects produced through surgery, which undoubtedly stimulate the body's self-repair function, but cannot truly reflect the osteogenic ability of new biomaterials [40]. Recently, Yaguu et al [41] reported that establishing the rat mandibular union as a congenital split jaw model is of great significance for clinical research.…”

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

“…Alteration of the quantity of EGCG and gelatin in AC-vhEGCG-GSs affected the bone formation results 18,24) . Although both AC-vhEGCG-GSs and vacuum-heated gelatin sponges successfully served as scaffolds for cells, the combination of AC-vhEGCG-GS with multipotent progenitor cells (dedifferentiated fat cells or adipose-derived stem cells) formed more bone in the congenital bone defects of rat jaws than the combination of vacuum-heated gelatin sponge with the above cells 25) . Additionally, the solution containing the EGCG-modified gelatin impaired RANKL-induced osteoclastogenesis and delayed tooth movement by hindering oxidation 26) .…”