Plant Flavonoid-Mediated Multifunctional Surface Modification Chemistry: Catechin Coating for Enhanced Osteogenesis of Human Stem Cells

Abstract

Application of surface chemistry using bioactive compounds enables simple functionalization of tissue-engineering scaffolds for improved biocompatibility and regenerative efficacy. Recently, surface modifications using natural polyphenols have been reported to serve as efficient multifunctional coating; however, there has yet to be any comprehensive application in tissue engineering. Here, we report a simple, multifunctional surface modification using catechin, a phenolic compound with many biological functions, found primarily in plants, to potentiate the functionality of polymeric scaffolds for bone regeneration by stem cells. We found that catechin hydrate can be efficiently deposited on the surface of various substrates and can greatly increase hydrophilicity of the substrates. While identifying the chemical mechanisms regulating catechin surface coating, we found that catechin molecules can self-assemble into dimers via cation−π interactions. Interestingly, the intrinsic biochemical functions of catechin coating provided the polymer scaffolds with antioxidative and calcium-binding abilities, resulting in enhanced adhesion, proliferation, mineralization, and osteogenic differentiation of human adipose-derived stem cells (hADSCs). Ultimately, catechin-functionalized polymer nanofiber scaffolds significantly promoted in vivo bone formation by hADSC transplantation in a critical-sized calvarial bone defect. Our study demonstrates that catechin can provide a biocompatible, multifunctional, and cost-effective surface modification chemistry to produce functional scaffolds with improved tissue regenerative efficacy.

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

“…However, our data is insufficient to conclude that the simple mixture of EGCG and gelatin was ineffective at retaining the polyphenol in the gelatin sponge. 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) .…”

“…Meanwhile, it is consensual that EGCG is a strong antioxidant and anti-inflammatory agent 8) . Additionally, the presence of EGCG in biomaterials treated by coating or modification approaches alters the materials properties, including wettability, charge, and calcium deposition 18,22) . After the transplantation of sponges, the rapid release of EGCG from NC-vhEGCG-GSs might have caused the loss of the pharmacological effect of EGCG and changed the surface properties of the sponges over time.…”

“…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) .…”

Bioinspired bone therapies using naringin: applications and advances

“…Such bioinspired approaches have recently shown promising pro-osteogenic potential for tissue engineering and regenerative medicine applications [4,8]. For example, a catechin-hydrate-coated substrate markedly enhanced the osteogenic differentiation and mineralization of hASCs [9]. In addition, catechin-coated polycaprolactone nanofiber scaffolds implanted in a critical-sized calvarial defect prompted a significant improvement in bone formation and density, as well as collagen deposition [9].…”

Phenolische Bausteine für die Assemblierung von Funktionsmaterialien

“…Die resultierenden Beschichtungen zeigten nicht nur antibakterielle und antioxidative Eigenschaften, sondern konnten auch zur Modulation der optischen Eigenschaften von anorganischen Nanopartikeln wie Gold‐Nanostäbchen verwendet werden (Abbildung d). Viele Beispiele sind gefolgt und ermöglichen eine große Familie von pflanzlichen Phenolverbindungen, die zur Oberflächenmodifikation durch oxidative Selbstpolymerisation verwendet werden können . Statt des basischen pH‐Bereichs kann auch UV‐Strahlung die oxidative Selbstpolymerisation von Phenolverbindungen induzieren; dieser Ansatz wurde zum Aufbau strukturierter dünner Schichten verwendet (Abbildung e–g) .…”