Mammalian tooth development relies heavily on the reciprocal and sequential interactions between cranial neural crest-derived mesenchymal cells and stomadial epithelium. During mouse tooth development, odontogenic potential, that is, the capability to direct an adjacent tissue to form a tooth, resides in dental epithelium initially, and shifts subsequently to dental mesenchyme. Recent studies have shown that mouse embryonic dental epithelium possessing odontogenic potential is able to induce the formation of a bioengineered tooth crown when confronted with postnatal mesenchymal stem cells of various sources. Despite many attempts, however, postnatal stem cells have not been used successfully as the epithelial component in the generation of a bioengineered tooth. We show here that epithelial sheets of cultured human keratinocytes, when recombined with mouse embryonic dental mesenchyme, are able to support tooth formation. Most significantly, human keratinocytes, recombined with mouse embryonic dental mesenchyme in the presence of exogenous FGF8, are induced to express the dental epithelial marker PITX2 and differentiate into enamel-secreting ameloblasts that develop a human-mouse chimeric whole tooth crown. We conclude that in the presence of appropriate odontogenic signals, human keratinocytes can be induced to become odontogenic competent; and that these are capable of participating in tooth crown morphogenesis and differentiating into ameloblasts. Our studies identify human keratinocytes as a potential cell source for in vitro generation of bioengineered teeth that may be used in replacement therapy.
Such future soft wearable electronics or wearable 2.0 products [8] will not be viable unless efficient reliable and skin-conformal power sources are to be developed. Most of the current wearable electronics are powered by rigid and bulky lithium-ion battery. Although paper batteries are emerging as a thinner version candidate, [9] they are still based on conventional metallic materials, which are neither stretchable nor compressive, unable to conformally be attached onto human skin. Typical smart soft electronics including wearable glucose sensors, pressure sensors, and surface electromyography (sEMG) only require a voltage of <100 mV and a power consumption of <20 µW, which could be supplied by different types of energy devices. [10] In this context, a variety of soft energy devices based on nanomaterials including batteries, [11] supercapacitors, [12,13] solar cells, [14] triboelectric nanogenerators, [15] and fuel cells [16-18] have attracted tremendous attention as the potential replacement of the lithium-ion battery to power skin-like electronics. Each type of those energy devices has their own intrinsic pros and cons. Wearable supercapacitors cannot provide continuous long-term energy supplies; [12,13] the performance of wearable photovoltaic devices is highly dependent on the external light source; [14] and the wearable nanogenerators based on piezoelectric and triboelectric devices can only provide intermittent energy and must be integrated with energy storage devices for continuous long-term monitoring. [15] Stretchable enzymatic biofuel cell that uses glucose or lactic acid in the body fluid to generate energy has been considered as an environmentally friendly power source for the next-generation skin-like energy devices. However, its performance is largely dependent on the stability of the enzyme, which may be easily affected by body temperature, pH, and fuel concentrations. [19,20] In contrast, fuel cells that use ethanol or methanol as a model system could offer a much higher power density and stability as they are not influenced by the biological environments. [21] A number of materials including silver nanowires, [22] carbon fibers, [23] graphene paper, [24] nickel foam, [25] vertically aligned gold nanowires (V-AuNWs) [26] have been demonstrated to fabricate flexible or even stretchable fuel cells. Nevertheless, high power output, skin-like device thickness, Skin-like energy devices can be conformally attached to the human body, which are highly desirable to power soft wearable electronics in the future. Here, a skin-like stretchable fuel cell based on ultrathin gold nanowires (AuNWs) and polymerized high internal phase emulsions (polyHIPEs) scaffolds is demonstrated. The polyHIPEs can offer a high porosity of 80% yet with an overall thickness comparable to human skin. Upon impregnation with electronic inks containing ultrathin (2 nm in diameter) and ultrahigh aspect-ratio (>10 000) gold nanowires, skin-like strain-insensitive stretchable electrodes are successfully fabricated. With such designed ...
Membranous extracellular matrix (ECM)-based scaffolds are one of the most promising biomaterials for skin wound healing, some of which, such as acellular dermal matrix, small intestinal submucosa, and amniotic membrane, have been clinically applied to treat chronic wounds with acceptable outcomes. Nevertheless, the wide clinical applications are always hindered by the poor mechanical properties, the uncontrollable degradation, and other factors after implantation. To highlight the feasible strategies to overcome the limitations, in this review, we first outline the current clinical use of traditional membranous ECM scaffolds for skin wound healing and briefly introduce the possible repair mechanisms; then, we discuss their potential limitations and further summarize recent advances in the scaffold modification and fabrication technologies that have been applied to engineer new ECM-based membranes. With the development of scaffold modification approaches, nanotechnology and material manufacturing techniques, various types of advanced ECM-based membranes have been reported in the literature. Importantly, they possess much better properties for skin wound healing, and would become promising candidates for future clinical translation.
Highly porous polymers produced by polymerization of the continuous phase of a high internal phase emulsion have been developed as scaffolds for 3D culture of human pluripotent stem cells. These emulsion‐templated polymerized high internal phase emulsion (polyHIPE) materials have an interconnected network of pores that provide support for the cells, while also allowing both cell ingress and nutrient diffusion. Thiol‐acrylate polyHIPE materials were prepared by photopolymerization, which, due to a competing acrylate homopolymerization process, leads to a material with residual surface thiols. These thiols were then used as a handle to allow postpolymerization functionalization with both maleimide and a maleimide‐derivatized cyclo‐RGDfK peptide, via Michael addition under benign conditions. Functionalization was evaluated using an Ellman's colorimetric assay, to monitor the residual thiol concentration, and X‐ray photoelectron spectroscopy. Maleimide was used as a model molecule to optimize conditions prior to peptide‐functionalization. The use of triethylamine as a catalyst and a mixed ethanol‐aqueous solvent system led to optimized reaction between surface‐bound thiols and maleimide. Peptide‐functionalized materials showed improved attachment and infiltration of human pluripotent stem cells over 7 days, demonstrating their promise as a scaffold for 3D stem cell culture and expansion. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1974–1981
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