Osteogenesis of Multipotent Progenitor Cells using the Epigallocatechin Gallate-Modified Gelatin Sponge Scaffold in 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 for dedifferentiated fat cells and adipose-derived stem cells and can induce bone regeneration in a rat congenial cleft-jaw model in vivo. Vacuum-heated gelatin sponge modified with EGCG (vhEGCG-GS) induced superior osteogenesis from these two cell types compared with vacuum-heated gelatin sponge (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.

Applications of Biomaterials in 3D Cell Culture and Contributions of 3D Cell Culture to Drug Development and Basic Biomedical Research

“…This method allows for easier and more detailed manufacturing than the above two methods and allows various architectures and control of mechanical stability [ 149 ]. The method can be applied to bone tissue engineering by taking advantage of its strong mechanical strength [ 150 ]. Chitosan material, which has been used as a soft scaffold in the form of a conventional hydrogel, can also be used for bone tissue engineering after reinforcement of its mechanical strength by applying this method.…”

On the road to smart biomaterials for bone research: definitions, concepts, advances, and outlook

“…88 The epigallocatechin gallate (EGCG) modification converted the positive surface potential of a gelatin sponge (+0.24 mV) to a negative surface potential (−0.54 mV), which lead to enhanced cell adhesion and calcium phosphate precipitation, and thus increased bone formation in a rat congenital cleft-jaw defect model. 89 Positively charged surfaces usually favor cell adhesion through electrostatic interactions with the negatively charged cell membranes. For example, poly(hydroxyethyl methacrylate) (pHEMA) with a high positive charge (+11 mV) had no significant effect on EphB4 activation or MSCs differentiation, as inferred from the low level of expression of osteogenic markers, including RUNX2, OCN, BSP, and OPN.…”

Innovative Molecular and Cellular Therapeutics in Cleft Palate Tissue Engineering

“…Examples include collagens, 85 gelatins, 86 silks, 87 fibrin, 88,89 and ECM, 90 some of which are available in medical grades and diverse forms (e.g., sponges, sheets, pastes, glues) and are approved by the U.S. Food and Drug Administration (FDA) for application in bone tissue engineering (e.g., Collapat Ò [BioMet, Inc.], BioGide [Geis-tlichPharma AG, Switzerland], and CollagraftÔ [Collagen Corp.]). 91 Multiple preclinical studies have utilized fibrin, 92,93 collagen, 92,[94][95][96][97] and gelatin 98 independently or in combination with other natural scaffold materials, including polysaccharides, proteins, and inorganic calcium solids, to successfully repair cleft palate bony defects in preclinical models. Collagen scaffolds have also been employed to manage alveolar clefts in 8-to 15-year-old human patients, 99 but secondary palatal cleft repair with natural scaffolds has not yet been reported in human infants.…”