The construction of biological scaffolds in vitro plays an important role in regenerative engineering, which has always been the focus of research. The application of scaffold materials combined with cells/bioactive factors is considered to have great potential for tissue regeneration. Various strategies have been used for constructing biological scaffolds, including electrospinning/spraying, direct laser writing, solvent casting, and microfluidic technology. Among them, considering the advantages of the safety, low cost, and highly controllable processing characteristics, microfluidic technology has become a promising method for the construction of biological scaffolds. This review overviews the recent research progress of microfluidic bioscaffolds for regenerative engineering. Firstly, we introduce some typical natural polymers which are widely used to construct bioscaffolds. Then, the bioscaffolds with different structures templated by microfluidic droplets and fibers are described. Furtherly, we talk about the different applications of microfluidic bioscaffolds in wound healing, drug delivery, bone regeneration, and nerve regeneration. Finally, the challenges and future prospects of the development of microfluidic bioscaffolds for regenerative engineering are discussed. 

Microfluidic Bioscaffolds for Regenerative Engineering

Achieving synergism, often by combination therapy via codelivery of chemotherapeutic agents, remains the mainstay of treating multidrug-resistance cases in cancer and microbial strains. With a typical core–shell architecture and surface functionalization to ensure facilitated targeting of tissues, nanocarriers are emerging as a promising platform toward gaining such synergism. Co-encapsulation of disparate theranostic agents in nanocarriers—from chemotherapeutic molecules to imaging or photothermal modalities—can not only address the issue of protecting the labile drug payload from a hostile biochemical environment but may also ensure optimized drug release as a mainstay of synergistic effect. However, the fate of co-encapsulated molecules, influenced by temporospatial proximity, remains unpredictable and marred with events with deleterious impact on therapeutic efficacy, including molecular rearrangement, aggregation, and denaturation. Thus, more than just an art of confining multiple therapeutics into a 3D nanoscale space, a co-encapsulated nanocarrier, while aiming for synergism, should strive toward achieving a harmonious cohabitation of the encapsulated molecules that, despite proximity and opportunities for interaction, remain innocuous toward each other and ensure molecular integrity. This account will inspect the current progress in co-encapsulation in nanocarriers and distill out the key points toward accomplishing such synergism through reciprocity.

Craft of Co-encapsulation in Nanomedicine: A Struggle To Achieve Synergy through Reciprocity

Research interest in nanoscale biomaterials has continued to grow in the past few decades, driving the need to form families of nanomaterials grouped by similar physical or chemical properties. Nanotubes have occupied a unique space in this field, primarily due to their high versatility in a wide range of biomedical applications. Although similar in morphology, members of this nanomaterial family widely differ in synthesis methods, mechanical and physiochemical properties, and therapeutic applications. As this field continues to develop, it is important to provide insight into novel biomaterial developments and their overall impact on current technology and therapeutics. In this review, we aim to characterize and compare two members of the nanotube family: carbon nanotubes (CNTs) and janus-base nanotubes (JBNts). While CNTs have been extensively studied for decades, JBNts provide a fresh perspective on many therapeutic modalities bound by the limitations of carbon-based nanomaterials. Herein, we characterize the morphology, synthesis, and applications of CNTs and JBNts to provide a comprehensive comparison between these nanomaterial technologies.

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Comparison between Janus-Base Nanotubes and Carbon Nanotubes: A Review on Synthesis, Physicochemical Properties, and Applications

Diabetes mellitus (DM) and its related complications are among the leading causes of disability and mortality worldwide. Substantial studies have explored epigenetic regulation that is involved in the modifications of DNA and proteins, but RNA modifications in diabetes are still poorly investigated. In recent years, posttranscriptional epigenetic modification of RNA (the so-called ‘epitranscriptome’) has emerged as an interesting field of research. Numerous modifications, mainly N6 -methyladenosine (m6A), have been identified in nearly all types of RNAs and have been demonstrated to have an indispensable effect in a variety of human diseases, such as cancer, obesity, and diabetes. Therefore, it is particularly important to understand the molecular basis of RNA modifications, which might provide a new perspective for the pathogenesis of diabetes mellitus and the discovery of new therapeutic targets. In this review, we aim to summarize the recent progress in the epitranscriptomics involved in diabetes and diabetes-related complications. We hope to provide some insights for enriching the understanding of the epitranscriptomic regulatory mechanisms of this disease as well as the development of novel therapeutic targets for future clinical benefit.

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Emerging Role of Epitranscriptomics in Diabetes Mellitus and Its Complications

Melatonin finely tunes proliferation and senescence in hematopoietic stem cells.

Background: The purpose of our research was to establish a gene signature and determine the prognostic value of m6A methylation regulators in cutaneous melanoma and WTAP as a protective gene in cutaneous melanoma prognosis, we also evaluated gene mutations in cutaneous melanoma. Methods: We downloaded the RNA-seq transcriptome data and the clinical information for cutaneous melanoma patients from the GTEx and TCGA databases. Consensus clustering analysis was applied to divide the samples into two groups. Then the least absolute shrinkage and selection operator (LASSO) analyses were conducted to construct a risk signature, and we use external and internal datasets to verify its predictive value. We further searched the cBioPortal tools to detect genomic alterations and WTAP mutations. Finally, WTAP was further identified as a prognostic factor, and the related mechanisms mediated by WTAP were predicted by gene set enrichment analysis (GSEA). Experimental validations and have been further carried out. Results: Notably, m6A RNA methylation regulators play significant roles in tumorigenesis and development. In total, we selected three subtypes of cutaneous melanoma according to consensus clustering of the m6A RNA methylation regulators, and the stage of cutaneous melanoma was proven to be related to the subtypes. The Cox regression and LASSO analyses built a risk signature including ELF3, ZC3H13 and WTAP. The prognostic value of the risk signature in internal and external datasets have been proven then. The whole-genome and selected gene WTAP mutations were further explored. WTAP as a single prognostic factor was also explored and found to serve as an independent protective prognostic factor. Conclusions: Our study constructed a stable risk signature composed of m6A RNA methylation regulators in cutaneous melanoma. Moreover, WTAP was identified as a valuable prognostic factor and potential molecular target for cutaneous melanoma treatment.

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Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous Melanoma.

Based on the phase separation phenomenon in micro-droplets, polymer-lipid Janus particles were prepared on a microfluidic flow focusing chip. Phase separation of droplets was caused by solvent volatilization and Janus morphology was formed under the action of interfacial tension. Because phase change from solid to liquid of the lipid hemisphere could be triggered by physiological temperature, the lipid hemisphere could be used for rapid release of drugs. While the polymer we selected was pH sensitive that the polymer hemisphere could degrade under acidic conditions, making it possible to release drugs in a specific pH environment, such as tumor tissues. Janus particles with different structures were obtained by changing the experimental conditions. To widen the application range of the particles, fatty alcohol and fatty acid-based phase change materials were also employed to prepare the particles, such as 1-tetradecanol, 1-hexadecanol and lauric acid. The melting points of these substances are higher than the physiological temperature, which can be applied in fever triggered drug release or in thermotherapy. The introduction of poly (lactic-co-glycolic acid) enabled the formation of multicompartment particles with three distinct materials. With different degradation properties of each compartment, the particles generated in this work may find applications in programmed and sequential drug release triggered by multiple stimuli.

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Microfluidic Preparation of Janus Microparticles With Temperature and pH Triggered Degradation Properties.

Melatonin is a hormone, synthesized in the pineal gland, which primarily controls the circadian rhythm of the body. In recent years, melatonin has also been shown to regulate metabolism, provide neuroprotection, and act as an anti-inflammatory, free radical scavenger. There has also been a recent research interest in the role of melatonin in regulating mesenchymal stromal cells (MSCs). MSCs are pivotal for their ability to differentiate into a variety of different tissues. There is also increasing evidence for the therapeutic prospects of MSCs via paracrine signaling. In addition to secreting cytokines and chemokines, MSCs can secrete extracellular vesicles (EVs), allowing them to respond to injury and promote tissue regeneration. While there has been a major research interest in the use of MSCs for regenerative medicine, the clinical application is limited by many risks, including tumorigenicity, senescence, and sensitivity to toxic environments. The use of MSC-derived EVs for cell-free therapy can potentially avoid the disadvantages of MSCs, which makes this an exciting prospect for regenerative medicine. Prior research has shown that MSCs, via paracrine mechanisms, can identify receptor-independent responses to melatonin and then activate a series of downstream pathways, which exert a variety of effects, including anti-tumor and anti-inflammatory effects. Here we review the synthesis of melatonin, its mechanisms of action, and the effect of melatonin on MSCs via paracrine signaling. Furthermore, we summarize the current clinical applications of melatonin and discuss future prospects.

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Zi-Yi Feng

Papers

Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous Melanoma.

Microfluidic Preparation of Janus Microparticles With Temperature and pH Triggered Degradation Properties.

Effect of Melatonin for Regulating Mesenchymal Stromal Cells and Derived Extracellular Vesicles.