Novel keratin preparation supports growth and differentiation of odontoblast‐like cells

Sharma, Lavanya Ajay; Ali, Mohammad Azam; Love, Robert M.; Wilson, Megan J.; Dias, George J.

doi:10.1111/iej.12476

Cited by 24 publications

(13 citation statements)

References 40 publications

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“…Current in vitro evidence suggests other potential drug delivery systems for bioactive molecules, such as biodegradable polymer matrix of lactide and glycolide (Mathieu et al 2013), porous silk fibroin scaffolds (Yang et al 2015), poly-2-hydroxyethyl methacrylate (polyHEMA)-based hydrogel (Takeda et al 2015), tricalcium phosphate microsphere-hydrogel composite (Lee et al 2014). In addition, biomaterials that can be used as scaffolds for VPT have recently been suggested and could enhance proliferation and differentiation of human dental pulp cells, such as polycaprolactone/submicron bioactive glass hybrid composites (Wang et al 2016a), a chitosan-based scaffold (Bellamy et al 2016) and keratin hydrogel (Sharma et al 2016).…”

Section: Current Challenges and Future Directionsmentioning

confidence: 99%

Disclosing the physiology of pulp tissue for vital pulp therapy

2018

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The discovery that dentine is a reservoir of bioactive molecules that can be recruited on demand has attracted efforts to develop new protocols and materials for vital pulp therapy (VPT). The noncollagenous proteins (NCPs) present in the dentine extracellular matrix (ECM) include growth factors (TGF-β1, BMP-7, FGF-2, IGF-1 and IGF-2, NGF and GDNF), extracellular matrix molecules (DSP, DPP, BSP, DMP-1 and DSPP) and both anti-inflammatory and pro-inflammatory chemokines and cytokines (TNF-α, IL-1, IL-6 and IL-10). Molecules such as DSP and DPP are mainly expressed by odontoblasts, and they are cleaved products from dentine sialophosphoprotein (DSPP). Some molecules, such as TGF-β1, specifically interact with decorin/biglycan in dentine. Although TGF-β1 increases the expression and secretion of NGF in human pulp cells, NGF induces mineralization and increases the expression of DSPP and DMP-1. Furthermore, GDNF may act as a cell survival factor and mitogen during tooth injury and repair. Pulp capping materials, such as MTA and calcium hydroxide, can solubilize bioactive dentine molecules (TGF-β1, NGF and GDNF) that stimulate tertiary dentinogenesis. The binding of these signalling molecules leads to activation of several signalling transduction pathways involved in dentinogenesis, odontoblast differentiation and inflammatory responses, such as the p38 MAPK, NF-kβ and Wnt/β-catenin signalling pathways. Understanding the cascade of cellular and molecular events underlying the repair and regeneration processes provides a reasonable new approach to VPT through a targeted interaction between tooth tissue and bioactive molecules.

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Section: Current Challenges and Future Directionsmentioning

confidence: 99%

Disclosing the physiology of pulp tissue for vital pulp therapy

2018

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“…This fibrous protein is present not only in the native ECM but also in different districts including wool, hair, fur, hooves, and feather. 20,21 Recent works demonstrated that keratin-based materials may be easily designed in the form of films, 22 hydrogels, 23,24 sponges, 25 fibers, 26 without altering the natural pathway of amino acid sequences, similarly to those required to promote cell adhesion in ECM. 21,27 In particular, wool keratin is biocompatible, biodegradable, nonimmunogenic, does not induce inflammatory response and promotes wound healing by stimulating human keratinocytes migration.…”

Section: Introductionmentioning

confidence: 99%

Highly polydisperse keratin rich nanofibers: Scaffold design and in vitro characterization

Cruz‐Maya

Guarino

Almaguer‐Flores

et al. 2019

J Biomedical Materials Res

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The use of bioactive proteins such as keratin has been successfully explored to improve the biological interface of scaffolds with cells during the tissue regeneration. In this work, it is optimized the fabrication of nanofibers combining wool keratin extracted by sulfitolysis, with polycaprolactone (PCL) in order to design bicomponent fibrous matrices able to exert a self‐adapting pattern of signals—morphological, chemical, or physical—confined at the single fiber level, to influence cell and bacteria interactions. It is demonstrated that the blending of highly polydisperse keratin with PCL (50:50) improves the stability of the electrospinning process, promoting the formation of nanofibers—144.1 ± 43.9 nm—without the formation of defects (i.e., beads, ribbons) typically recognized in the fabrication of keratin ones. Moreover, keratin drastically increases the fiber hydrophilicity—compared with PCL fiber alone—thus improving the hMSC adhesion and in vitro proliferation until 14 days. Moreover, the growth of bacterial strains (i.e., Escherichia coli and Staphylococcus aureus) seems to be not specifically inhibited by the contribution of keratin, so that the integration of further selected compounds (i.e., metal ions) is suggested to more efficiently fight against bacteria resistance, to make them suitable for the regeneration of different interfaces and soft tissues (i.e., skin and cornea). © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1803–1813, 2019.

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“…Indeed, woolderived keratin presents both RGD and LDV cell adhesion sequences. 43,44 These sequences bind ανβ3 and α4β1 integrins overexpressed on the endothelium of the tumor neovasculature and on many types of cancer cells. [45][46][47] To investigate the ability of our innovative delivery system to vehiculate PTX to cells grown in 2D model, we took advantage of PTX labeled with a thiophene-based fluorescent dye (PTX-F35), a previously reported fluorescent PTX derivative, 48 to perform cytofluorimetric uptake assays over time.…”

Section: Discussionmentioning

confidence: 99%

Anticancer activity of paclitaxel-loaded keratin nanoparticles in two-dimensional and perfused three-dimensional breast cancer models

Foglietta¹,

Spagnoli²,

Muraro³

et al. 2018

IJN

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PurposeTaxanes are highly effective cytotoxic drugs for progressing breast cancer treatment. However, their poor solubility and high toxicity urge the development of innovative formulations of potential clinical relevance.Materials and methodsBy using a simple and straightforward aggregation method, we have generated paclitaxel (PTX) loaded in keratin nanoparticles (KER-NPs-PTX). Their activities were tested against human breast cancer MCF-7 and MDA MB 231 cell lines in conventional two-dimensional (2D) cultures and in a dynamic three-dimensional (3D) model with perfused bioreactor (p3D). Moreover, KER-NPs-PTX activity was compared to free PTX and to PTX loaded in albumin nanoparticles (HSA-NPs-PTX). Cell viability, induction of apoptosis, and gene expression analysis were used as readouts.ResultsIn 2D cultures, KER-NPs-PTX was able to inhibit tumor cell viability and to induce apoptosis similarly to PTX and HSA-NPs-PTX. In the p3D model, a lower sensitivity of tumor cells to treatments was observed. Importantly, only KER-NPs-PTX was able to induce a statistically significant increase in apoptotic cell percentages following 24 h treatment for MCF-7 (16.7±4.0 early and 11.3±4.9 late apoptotic cells) and 48 h treatment for MDA MB 231 (21.3±11.2 early and 10.5±1.8 late apoptotic cells) cells. These effects were supported, at least for MCF-7 cells, by significant increases in the expression of proapoptotic BAX gene (5.8±0.5) 24 h after treatment and of cleaved caspase 3 (CC3) protein.ConclusionKER-NPs-PTX, generated by a simple procedure, is characterized by high water solubility and enhanced PTX-loading ability, as compared to HSA-NPs-PTX. Most importantly, it appears to be able to exert effective anticancer activities on breast cancer cells cultured in 2D or in p3D models.

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Novel keratin preparation supports growth and differentiation of odontoblast‐like cells

Abstract: The presence of keratin enhanced odontoblast cell behaviour. Keratin hydrogels may be a potential scaffold for pulp-dentine regen-eration.

Cited by 24 publications

References 40 publications

Disclosing the physiology of pulp tissue for vital pulp therapy

Disclosing the physiology of pulp tissue for vital pulp therapy

Highly polydisperse keratin rich nanofibers: Scaffold design and in vitro characterization

Anticancer activity of paclitaxel-loaded keratin nanoparticles in two-dimensional and perfused three-dimensional breast cancer models

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