MXenes—A New Class of Two-Dimensional Materials: Structure, Properties and Potential Applications

A new class of two-dimensional nanomaterials, MXenes, which are carbides/nitrides/carbonitrides of transition and refractory metals, has been critically analyzed. Since the synthesis of the first family member in 2011 by Yury Gogotsi and colleagues, MXenes have quickly become attractive for a variety of research fields due to their exceptional properties. Despite the fact that this new family of 2D materials was discovered only about ten years ago, the number of scientific publications related to MXene almost doubles every year. Thus, in 2021 alone, more than 2000 papers are expected to be published, which indicates the relevance and prospects of MXenes. The current paper critically analyzes the structural features, properties, and methods of synthesis of MXenes based on recent available research data. We demonstrate the recent trends of MXene applications in various fields, such as environmental pollution removal and water desalination, energy storage and harvesting, quantum dots, sensors, electrodes, and optical devices. We focus on the most important medical applications: photo-thermal cancer therapy, diagnostics, and antibacterial treatment. The first results on obtaining and studying the structure of high-entropy MXenes are also presented

MEK and TGF-beta Inhibition Promotes Reprogramming without the Use of Transcription Factor

<div><p>The possibility of replacing the originally discovered and widely used DNA reprogramming transcription factors is stimulating enormous effort to identify more effective compounds that would not alter the genetic information. Here, we describe the generation of induced pluripotent stem cells (iPSc) from head-derived primary culture of mouse embryonic cells using small chemical inhibitors of the MEK and TGF-beta pathways without delivery of exogenous transcription factors. These iPSc express standard pluripotency markers and retain their potential to differentiate into cells of all germ layers. Our data indicate that head-derived embryonic neural cells might have the reprogramming potential while neither the same primary cells cultivated over five passages <i>in vitro</i> nor a cell population derived from adult brain possesses this capacity. Our results reveal the potential for small molecules to functionally replace routinely used transcription factors and lift the veil on molecular regulation controlling pluripotency. The conditions described here could provide a platform upon which other genome non integrative and safer reprogramming processes could be developed. This work also shows novel potential for developing embryonic neural cells.</p></div

Combination of heterologous fibrin sealant and bioengineered human embryonic stem cells to improve regeneration following autogenous sciatic nerve grafting repair

Abstract Background Peripheral nerve injury is a worldwide clinical problem, and the preferred surgical method for treating it is the end-to-end neurorrhaphy. When it is not possible due to a large nerve gap, autologous nerve grafting is used. However, these surgical techniques result in nerve regeneration at highly variable degrees. It is thus very important to seek complementary techniques to improve motor and sensory recovery. One promising approach could be cell therapy. Transplantation therapy with human embryonic stem cells (hESCs) is appealing because these cells are pluripotent and can differentiate into specialized cell types and have self-renewal ability. Therefore, the main objective of this study was to find conditions under which functional recovery is improved after sciatic nerve neurorrhaphy. We assumed that hESC, either alone or in combination with heterologous fibrin sealant scaffold, could be used to support regeneration in a mouse model of sciatic nerve injury and repair via autografting with end-to-end neurorrhaphy. Methods Five millimeters of the sciatic nerve of C57BL/6 J mice were transected off and rotated 180 degrees to simulate an injury, and then stumps were sutured. Next, we applied heterologous fibrin sealant and/or human embryonic stem cells genetically altered to overexpress fibroblast growth factor 2 (FGF2) at the site of the injury. The study was designed to include six experimental groups comprising neurorrhaphy (N), neurorrhaphy + heterologous fibrin sealant (N + F), neurorrhaphy + heterologous fibrin sealant + doxycycline (N + F + D), neurorrhaphy + heterologous fibrin sealant + wild-type hESC (N + F + W), neurorrhaphy + heterologous fibrin sealant + hESC off (N + F + T), and neurorrhaphy + heterologous fibrin sealant + hESC on via doxycycline (N + F + D + T). We evaluated the recovery rate using Catwalk and von Frey functional recovery tests, as well as immunohistochemistry analysis. Results The experiments indicated that sensory function improved when transgenic hESCs were used. The regeneration of sensory fibers indeed led to increased reflexes, upon stimulation of the paw ipsilateral to the lesion, as seen by von-Frey evaluation, which was supported by immunohistochemistry. Conclusions Overall, the present data demonstrated that transgenic embryonic stem cells, engineered to overexpress FGF-2 in an inducible fashion, could be employed to support regeneration aiming at the recovery of both motor and sensory functions

Expression of pluripotency markers in chiPSc colonies.

<p>Left column: staining of nuclei using DAPI (blue). Right column: the same colony stained with antibodies against several pluripotency markers including, Oct4, Sox2, Ssea1 and Nanog. Oct4- and Nanog-positive colonies are enlarged to show specificity of the staining in comparison to surrounding fibroblasts. 100x magnification was used for Oct4, Ssea1 and Nanog, 200x magnification for Sox2.</p

Timescale of the reprogramming experiment and combinations of inhibitors.

<p><b>[A]</b> Cell culture was seeded at concentration of 25,000–33,000 cells/cm² at day 0 (1.7 x 10^6 cells per 10cm dish). On days 1, 2 and 4 the inhibitors PD0325901 and SB431542 were applied at concentrations 0.5 μM and 2 μM. Cultures were three times replated (1:3 ratio) as indicated by a triple arrow. At day 25, the first colonies positive for alkaline phosphatase were detected (brown bar) and MEF culture medium was replaced by LIF–containing ESM medium (blue bar). In parallel experiments, fibroblast cultures were treated with mir294 mimics (days 1, 3 and 7) and p53 inhibitor (days 4 and 6). <b>[B]</b> Combinations of inhibitors for chiPSc reprogramming as applied on individual plates (experimental setup 1–9) with the number of resulting morphologically distinguishable and phosphatase positive iPSc-like colonies from four independent experiments in each setup.</p

Histological characterization of chiPSc-derived teratomas.

<p>Two independent chiPSc lines (two replicas of each line) were tested in nude mice. Histological sections of hematoxylin-and-eosin-stained sections of teratomas from both lines consist of tissues from all three germ layers. A) Adipose-like tissue [Ad], muscle [Mu]; B) bone; C,D) gut-like epithelial structures with mature goblet cells; E) neuroblastic tissue with neuronal rosettes; F,G) epidermis; and H) cartilage. Magnified 100x.</p

Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs)

Dorsal root rhizotomy (DRZ) is currently considered an untreatable injury, resulting in the loss of sensitive function and usually leading to neuropathic pain. In this context, we recently proposed a new surgical approach to treat DRZ that uses platelet-rich plasma (PRP) gel to restore the spinal reflex. Success was correlated with the reentry of primary afferents into the spinal cord. Here, aiming to enhance previous results, cell therapy with bioengineered human embryonic stem cells (hESCs) to overexpress fibroblast growth factor 2 (FGF2) was combined with PRP. For these experiments, adult female rats were submitted to a unilateral rhizotomy of the lumbar spinal dorsal roots, which was followed by root repair with PRP gel with or without bioengineered hESCs. One week after DRZ, the spinal cords were processed to evaluate changes in the glial response (GFAP and Iba-1) and excitatory synaptic circuits (VGLUT1) by immunofluorescence. Eight weeks postsurgery, the lumbar intumescences were processed for analysis of the repaired microenvironment by transmission electron microscopy. Spinal reflex recovery was evaluated by the electronic Von Frey method for eight weeks. The transcript levels for human FGF2 were over 37-fold higher in the induced hESCs than in the noninduced and the wildtype counterparts. Altogether, the results indicate that the combination of hESCs with PRP gel promoted substantial and prominent axonal regeneration processes after DRZ. Thus, the repair of dorsal roots, if done appropriately, may be considered an approach to regain sensory-motor function after dorsal root axotomy