Catechol Chemistry Research Articles

Polydopamine-Assisted Osteoinductive Peptide Immobilization of Polymer Scaffolds for Enhanced Bone Regeneration by Human Adipose-Derived Stem Cells

Immobilization of osteoinductive molecules, including growth factors or peptides, on polymer scaffolds is critical for improving stem cell-mediated bone tissue engineering. Such molecules provide osteogenesis-stimulating signals for stem cells. Typical methods used for polymeric scaffold modification (e.g., chemical conjugation or physical adsorption), however, have limitations (e.g., multistep, complicated procedures, material denaturation, batch-to-batch inconsistency, and inadequate conjugation) that diminish the overall efficiency of the process. Therefore, in this study, we report a biologically inspired strategy to prepare functional polymer scaffolds that efficiently regulate the osteogenic differentiation of human adipose-derived stem cells (hADSCs). Polymerization of dopamine (DA), a repeated motif observed in mussel adhesive protein, under alkaline pH conditions, allows for coating of a polydopamine (pDA) layer onto polymer scaffolds. Our study demonstrates that predeposition of a pDA layer facilitates highly efficient, simple immobilization of peptides derived from osteogenic growth factor (bone morphogenetic protein-2; BMP-2) on poly(lactic-co-glycolic acid) (PLGA) scaffolds via catechol chemistry. The BMP-2 peptide-immobilized PLGA scaffolds greatly enhanced in vitro osteogenic differentiation and calcium mineralization of hADSCs using either osteogenic medium or nonosteogenic medium. Furthermore, transplantation of hADSCs using pDA-BMP-2-PLGA scaffolds significantly promoted in vivo bone formation in critical-sized calvarial bone defects. Therefore, pDA-mediated catechol functionalization would be a simple and effective method for developing tissue engineering scaffolds exhibiting enhanced osteoinductivity. To the best of our knowledge, this is the first study demonstrating that pDA-mediated surface modification of polymer scaffolds potentiates the regenerative capacity of human stem cells for healing tissue defect in vivo.

Long-Lasting Antifouling Coating from Multi-Armed Polymer

We describe a new antifouling surface coating, based on aggregation of a short amphiphilic four-armed PEG-dopamine polymer into particles and on surface binding by catechol chemistry. An unbroken and smooth polymeric coating layer with an average thickness of approximately 4 μm was formed on top of titanium oxide surfaces by a single step reaction. Coatings conferred excellent resistance to protein adhesion. Cell attachment was completely prevented for at least eight weeks, although the membranes themselves did not appear to be intrinsically cytotoxic. When linear PEG or four-armed PEG of higher molecular weight were used, the resulting coatings were inferior in thickness and in preventing protein adhesion. This coating method has potential applicability for biomedical devices susceptible to fouling after implantation.

Peptide decorated nano-hydroxyapatite with enhanced bioactivity and osteogenic differentiation via polydopamine coating

To be better used as implant materials in bone graft substitutes, bioactivity and osteogenesis of nano-hydroxyapatite (nano-HA) need to be further enhanced. Inspired by adhesive proteins in mussels, here we developed a novel bone forming peptide decorated nano-HA material. In this study, nano-HA was coated by one-step pH-induced polymerization of dopamine, and then the peptide was grafted onto polydopamine (pDA) coated nano-HA (HA-pDA) through catechol chemistry. Our results demonstrated that the peptide-conjugated nano-HA crystals could induce the adhesion and proliferation of MG-63 cells. Moreover, the highly alkaline phosphatase activity of the functionalized nano-HA indicated that the grafted peptide could maintain its biological activity after immobilization onto the surface of HA-pDA, especially at the concentration of 100μg/mL. These modified nano-HA crystals with better bioactivity and osteogenic differentiation hold great potential to be applied as bioactive materials in bone repairing, bone regeneration and bio-implant coating applications.

Triggered pH/redox responsive release of doxorubicin from prepared highly stable graphene with thiol grafted Pluronic

Strategy, to develop stable graphene and well control hydrophobic drug release from the prepared graphene, is reported to achieve a biomedical platform in drug delivery system. Reduced graphene oxide (rGO) has been prepared using quaternized 2-chloro-3',4'-dihydroxyacetophenone to poly(ethylene glycol)-g-poly(dimethylaminoethyl methacrylate) [PEG-g-PDMA, QC-PEG] following catechol chemistry which exhibited excellent dispersibility in water. Installation of thiol grafted Pluronic (Plu-SH) results formation of disulfide bonds surrounding rGO/QC-PEG matrix and further aids to achieve high DOX loading efficiency as well as trigged responsive controlled release behavior of DOX from the matrixes by redox responsive Plu-SH and pH sensitive. The rGO/QC-PEG with Plu-SH matrix showed significant stability under different physiological conditions. In vitro DOX release was conducted against different reductive environment and at different pH to figure out the release kinetics. Investigation from MTT assay assures more biocompatible behavior of rGO/QC-PEG/Plu-SH than prepared reduced graphene oxide. Effects of introducing Plu-SH was flashed when QDs loaded rGO/QC-PEG was applied to cell and examining the emitted fluorescence behavior from the cell by confocal images. The confocal investigation showed that high quenching effect of graphene is an obstacle to trace their position if it is used in cell tracking where application of Plu-SH could minimize this.

Successful stabilization of functionalized hybrid graphene for high-performance antimicrobial activity

We have prepared an antimicrobial nanocomposite composed of reduced graphene oxide (rGO) using antimicrobial agents and catechol derivative conjugated to polyethylene glycol-grafted poly(dimethylaminoethyl methacrylate) (PEG-g-PDMA). Graphene oxide (GO) has been simultaneously reduced by 2-chloro-3′,4′-dihydroxyacetophenone (CCDP) in Tris buffer at pH 8.5 following catechol chemistry. Both CCDP and antimicrobial agent 1-bromododecane (C12) were quaternized to PEG-g-PDMA (CCDP-C12)-q-(PEG-g-PDMA). This synthesized polymer functionalized rGO as an antimicrobial nanocomposite, rGO/(CCDP-C12)-q-(PEG-g-PDMA). To increase antimicrobial activity, silver nanoparticles (Ag NPs) were deposited onto the high surface area of rGO/(CCDP-C12)-q-(PEG-g-PDMA). The prepared antimicrobial nanocomposite shows significant stability in aqueous media due to the hydrophilic behaviour of PEG. X-ray photoelectron spectroscopy investigation clearly shows the quaternization of C-12 and deposition of Ag NPs onto rGO surfaces. Ag NP-deposited rGO/(CCDP-C12)-q-(PEG-g-PDMA) shows better antimicrobial activity both against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria at lower concentration compared to without applying Ag NPs. Investigation of the cytotoxicity demonstrates outstanding non-toxic properties of both the prepared nanocomposite as well as the synthesized polymer.

Biopolymer functionalized reduced graphene oxide with enhanced biocompatibility via mussel inspired coatings/anchors.

A green and facile method for preparing biopolymer functionalized reduced graphene oxide (RGO) by using mussel inspired dopamine (DA) as the reducing reagent and the functionalized molecule is proposed. In the study, GO is reduced by DA and DA is adhered to RGO by one-step pH-induced polymerization of DA (polydopamine, PDA), and then heparin or protein is grafted onto the PDA adhered RGO (pRGO) through catechol chemistry. The obtained pRGO, heparin grafted pRGO (Hep-g-pRGO), and BSA grafted pRGO (BSA-g-pRGO) exhibit fine 2D morphology and excellent stability in water and PBS solution. Furthermore, the biocompatibility of the biopolymer functionalized RGO are investigated using human blood cells and human umbilical vein endothelial cells (HUVECs). The biopolymer functionalized RGO exhibits an ultralow hemolysis ratio (lower than 1.8%), and the cellular toxicity assay suggests that the biopolymer functionalized RGO has good cytocompatibility for HUVEC cells, even at a high concentration of 100 μg mL-1. Moreover, the high anticoagulant ability of Hep-g-pRGO indicates that the grafted biopolymer could maintain its biological activity after immobilization onto the surface of pRGO. Therefore, the proposed safe and green biomimetic method confers the biopolymer functionalized RGO with great potential for various biological and biomedical applications.

Bio-inspired catechol chemistry for electrophoretic nanotechnology of oxide films

Bio-inspired chemical approach has been developed for the surface modification and electrophoretic deposition of manganese dioxide and zirconia nanoparticles, prepared by chemical precipitation methods. Caffeic acid, trans-cinnamic acid, p-coumaric acid, and 2,4-dihydroxycinnamic acid were investigated for the surface modification of the nanoparticles. The influence of the structure of the organic molecules on their adsorption on the oxide nanoparticles has been investigated. The mechanism of caffeic acid adsorption was similar to that of natural catecholic amino acid, l-3,4-dihydroxyphenylalanine. The use of caffeic acid allowed for agglomerate-free synthesis, efficient dispersion, charging, electrophoretic deposition and co-deposition of manganese dioxide and zirconia nanoparticles. The deposition yield data, coupled with the results of thermogravimetric analysis, X-ray diffraction analysis, and Fourier transform infrared spectroscopy, showed that surface chemistry, rather than the crystal structure, determined the adsorption behavior. Electron microscopy and energy dispersive spectroscopy investigations showed the formation of nanostructured oxide films and composites. The deposit composition can be varied.

Bio-inspired catechol chemistry: a new way to develop a re-moldable and injectable coacervate hydrogel

A new way is demonstrated to develop a bio-inspired coacervate hydrogel by following catechol chemistry showing injectable and re-moldable physical properties. The formed coacervate shows potential long-term stability under water. Depending on pH, formation of the coacervate has been verified which is confirmed by XPS and zeta potential measurements.

Cytocompatible Encapsulation of Individual Chlorella Cells within Titanium Dioxide Shells by a Designed Catalytic Peptide

The individual encapsulation of living cells has a great impact on the areas of single cell-based sensors and devices as well as fundamental studies in single cell-based biology. In this work, living Chlorella cells were encapsulated individually with abiological, functionalizable TiO(2), by a designed catalytic peptide that was inspired by biosilicification of diatoms in nature. The bioinspired cytocompatible reaction conditions allowed the encapsulated Chlorella cells to maintain their viability and original shapes. After formation of the TiO(2) shells, the shells were postfunctionalized by using catechol chemistry. Our work suggests a bioinspired approach to the interfacing of individual living cells with abiological materials in a controlled manner.

Controlled synthesis of PEI-coated gold nanoparticles using reductive catechol chemistry for siRNA delivery

Development of nano-sized gene delivery vehicles for small interfering RNA (siRNA) delivery is of great importance for their clinical applications such as cancer therapy. Herein, we demonstrate the controlled synthesis of polyethyleneimine (PEI)-coated gold nanoparticles (AuNPs) using catechol-conjugated PEI (PEI-C) for siRNA delivery. Since the conjugated catechol groups are reductive and moderately hydrophobic, PEI-C formed spherical multi-cored micelles in aqueous solution and served as reductive templates for the growth and synthesis of spherical AuNPs with tunable sizes and surface charges. PEI-C was stably anchored on the surface of growing crystal gold seeds with crosslinking, resulting in robust cationic AuNPs. The fabricated PEI-coated AuNPs formed stable complexes with siRNA, and the complexes showed an excellent gene silencing effect in cancer cells. Size and surface charge values of the synthesized AuNPs had a great influence on intracellular uptake and unpacking of siRNA, and the resultant gene silencing efficiency. The PEI-coated AuNPs exhibited an extremely low cytotoxicity due to the reduced density of primary amine groups and the absence of uncomplexed PEI fraction in aqueous solution.