Microfluidic 3D printing polyhydroxyalkanoates-based bionic skin for wound healing

Biomimetic scaffolds with extracellular matrix (ECM)-mimicking structure have been widely investigated in wound healing applications, while insufficient mechanical strength and limited biological activity remain major challenges. Here, we present a microfluidic 3D printing biomimetic polyhydroxyalkanoates-based scaffold with excellent mechanical properties and hierarchical porous structures for enhanced wound healing. This scaffold is composed of poly(3-hydroxybutyrate-4-hydroxybutyrate) (P34HB) and polycaprolactone (PCL), endowing it with excellent tensile strength (2.99 MPa) and degradability (80% of weight loss within 7 days). The ECM-mimicking hierarchical porous structure allows bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) to proliferate and adhere on the scaffolds. Besides, anisotropic composite scaffolds loaded with BMSCs and HUVECs can significantly promote re-epithelization, collagen deposition and capillary formation in rat wound defects, indicating their satisfactory in vivo tissue regenerative activity. These results indicate the feasibility of polyhydroxyalkanoates-based biomimetic scaffolds for skin repair and regeneration, which also provide a promising therapeutic strategy in diverse tissue engineering applications.

Biomaterials for Cell-Surface Engineering and Their Efficacy

Literature in the field of stem cell therapy indicates that, when stem cells in a state of single-cell suspension are injected systemically, they show poor in vivo survival, while such cells show robust cell survival and regeneration activity when transplanted in the state of being attached on a biomaterial surface. Although an attachment-deprived state induces anoikis, when cell-surface engineering technology was adopted for stem cells in a single-cell suspension state, cell survival and regenerative activity dramatically improved. The biochemical signal coming from ECM (extracellular matrix) molecules activates the cell survival signal transduction pathway and prevents anoikis. According to the target disease, various therapeutic cells can be engineered to improve their survival and regenerative activity, and there are several types of biomaterials available for cell-surface engineering. In this review, biomaterial types and application strategies for cell-surface engineering are presented along with their expected efficacy.

An NRF2 Perspective on Stem Cells and Ageing

Redox and metabolic mechanisms lie at the heart of stem cell survival and regenerative activity. NRF2 is a major transcriptional controller of cellular redox and metabolic homeostasis, which has also been implicated in ageing and lifespan regulation. However, NRF2’s role in stem cells and their functioning with age is only just emerging. Here, focusing mainly on neural stem cells, which are core to adult brain plasticity and function, we review recent findings that identify NRF2 as a fundamental player in stem cell biology and ageing. We also discuss NRF2-based molecular programs that may govern stem cell state and function with age, and implications of this for age-related pathologies.

Interference of LPS H. pylori with IL-33-Driven Regeneration of Caviae porcellus Primary Gastric Epithelial Cells and Fibroblasts

Background: Lipopolysaccharide (LPS) of Helicobacter pylori (Hp) bacteria causes disintegration of gastric tissue cells in vitro. It has been suggested that interleukin (IL)-33 is involved in healing gastric injury. Aim: To elucidate whether Hp LPS affects regeneration of gastric barrier initiated by IL-33. Methods: Primary gastric epithelial cells or fibroblasts from Caviae porcellus were transfected with siRNA IL-33. Such cells, not exposed or treated with LPS Hp, were sub-cultured in the medium with or without exogenous IL-33. Then cell migration was assessed in conjunction with oxidative stress and apoptosis, activation of extracellular signal-regulated kinase (Erk), production of collagen I and soluble ST2 (IL-33 decoy). Results: Control cells not treated with LPS Hp migrated in the presence of IL-33. The pro-regenerative activity of IL-33 was related to stimulation of cells to collagen I production. Wound healing by cells exposed to LPS Hp was inhibited even in the presence of IL-33. This could be due to increased oxidative stress and apoptosis in conjunction with Erk activation, sST2 elevation and modulation of collagen I production. Conclusions: The recovery of gastric barrier cells during Hp infection potentially can be affected due to downregulation of pro-regenerative activity of IL-33 by LPS Hp.

Engineering an alginate/β-glycerophosphate/dextran injectable hydrogel-delivery for cardiac therapies after acute myocardial infarctions

Human mesenchymal stem cell therapy (hMSCs) enables the transmission of alginate (A)/dextran (D)/β- glycerophosphate (β-GP) to the human myocardials infarcts. The fabricated hMSCs-AD@β-GP exhibited pixelation rate, pore size, absorbency, and aggregation rate values of 65.3%, 146.2%, 92.0%, and 29.1% with 1%, respectively. The hMSCs-AD@β-GP produced were physiochemically examined and were found to be highly stable, verifying the usefulness of the nanomaterials for cardiac regenerations. The in vitro studies of hMSCs- AD@β-GP hydrogels have indicated that the cell survival ratio improved, and the positive findings of ejection fraction, fibrosis, and vessel density with lowered infraction size indicated that the heart regenerative activity also improved significantly after myocardial infraction. The synergic effect of the hydrogel with hMSCs-AD@β- GP may, therefore, be suitable to treat patients with severe myocardial infarctions.

Regenerative potential of mesenchymal stem cell derived extracellular vesicles

: Mesenchymal stem cells (MSCs) are considered multipotent cells that can differentiate into diverse cell lineages. MSCs based therapy has become a widely experimented treatment strategy in regenerative medicine with promising outcomes. Recent reports suggest that much of the therapeutic effects of MSCs are mediated by their secretome that is expressed through extracellular vesicles (EVs). EVs are lipid bilayer bound components that cargo cellular proteins, mRNA, lncRNAs and other molecules in order to mediate intercellular communication and signaling. In fact, MSC derived EVs have been observed to implement the same therapeutic effects as MSCs with minimal adverse effects and could be used as an alternative treatment method to MSC based therapy. The regenerative activity of MSC-EVs has been observed in relation to multiple cell/tissue lineages using various animal models. However, further research and clinical trials are essential for the advancement of this novel treatment strategy. This review provides an insight into the available literature on applications of MSC-EVs in relation to angiogenesis, neurogenesis, hepatic and kidney regeneration and wound healing.

Defined MSC exosome with high yield and purity to improve regenerative activity

Exosomes derived from mesenchymal stem cells (MSCs) have been studied as vital components of regenerative medicine. Typically, various isolation methods of exosomes from cell culture medium have been developed to increase the isolation yield of exosomes. Moreover, the exosome-depletion process of serum has been considered to result in clinically active and highly purified exosomes from the cell culture medium. Our aim was to compare isolation methods, ultracentrifuge (UC)-based conventional method, and tangential flow filtration (TFF) system-based method for separation with high yield, and the bioactivity of the exosome according to the purity of MSC-derived exosome was determined by the ratio of Fetal bovine serum (FBS)-derived exosome to MSC-derived exosome depending on exosome depletion processes of FBS. The TFF-based isolation yield of exosome derived from human umbilical cord MSC (UCMSC) increased two orders (92.5 times) compared to UC-based isolation method. Moreover, by optimizing the process of depleting FBS-derived exosome, the purity of UCMSC-derived exosome, evaluated using the expression level of MSC exosome surface marker (CD73), was about 15.6 times enhanced and the concentration of low-density lipoprotein-cholesterol (LDL-c), known as impurities resulting from FBS, proved to be negligibly detected. The wound healing and angiogenic effects of highly purified UCMSC-derived exosomes were improved about 23.1% and 71.4%, respectively, with human coronary artery endothelial cells (HCAEC). It suggests that the defined MSC exosome with high yield and purity could increase regenerative activity.