Physiological Manner Research Articles

Manufacture of PCL scaffolds through electrospinning technology to accommodate Triple Negative Breast Cancer cells culture

Abstract Two-dimensional (2D) cell culture structures are demonstrated to differ from the in vivo environment. Therefore, cells adopt a flattened morphology that may lead to a non-physiological behaviour. For instance, 2D culture induces the differentiation of the cancer stem cells (CSCs), a tumorigenic cell niche whose study is crucial in tumors with a high relapse rate such as the triple negative breast cancer (TNBC). As an alternative, electrospun scaffolds which mimic the native extracellular matrix structure have emerged as a three-dimensional culture support. In this work, two different meshes of 7.5 and 15% of poly(e-caprolactone) (PCL) were fabricated, differentiating in their microstructure. Scaffolds exhibited similar DSC and TGA curves compared with raw PCL, indicating their purity. TNBC MDA-MB-468 cells were seeded on scaffolds and adopted a more elongated morphology when cultured on 15% PCL meshes. Hence, electrospinning PCL scaffolds may become a suitable tool to culture TNBC cells in a more physiological manner.

Neutrophil Modulation in Alpha-1 Antitrypsin Deficiency.

Neutrophils have been implicated in the pathogenesis of alpha-1 antitrypsin deficiency (AATD) since the first descriptions of the disease. Neutrophil proteinases can cause all lung manifestations of AATD, from small airways destruction, to emphysema, to chronic bronchitis and airflow obstruction. Initially, it was proposed that neutrophil functions were normal in AATD, responding in an initially physiological manner to a high burden of pulmonary inflammation. More recent studies have shed new light on this, describing changes in neutrophil responses (a modulation of usual cellular functions) in the presence of inflammation or infection which might enhance tissue damage while impeding bacterial clearance, providing some evidence to support there being an AATD neutrophil phenotype. Many facets of neutrophil function in AATD can be explained by the loss of alpha-1 antitrypsin (AAT) in diverse biological processes. If this were the only reason for altered neutrophil functions, one would predict similar disease presentation across affected people. However, this is not the case. Despite similar (low) levels of AAT, lung disease is extremely variable in AATD, with some patients suffering a significant burden of lung disease and some much less, irrespective of smoking habits and, in some cases, despite augmentation therapy. This review will explore how complex neutrophil responses are and how they are altered with age, inflammation and AATD. Further, it will discuss the need to understand more completely which aspects of AATD-associated disease are driven by neutrophils and how patients more susceptible to neutrophil dysfunction could be identified to potentially stratify treatment approaches.

SINEUP Non-coding RNA Targeting GDNF Rescues Motor Deficits and Neurodegeneration in a Mouse Model of Parkinson's Disease.

Glial cell-derived neurotrophic factor (GDNF) has a potent action in promoting the survival of dopamine (DA) neurons. Several studies indicate that increasing GDNF levels may be beneficial for the treatment of Parkinson’s disease (PD) by reducing neurodegeneration of DA neurons. Despite a plethora of preclinical studies showing GDNF efficacy in PD animal models, its application in humans remains questionable for its poor efficacy and side effects due to its uncontrolled, ectopic expression. Here we took advantage of SINEUPs, a new class of antisense long non-coding RNA, that promote translation of partially overlapping sense protein-coding mRNAs with no effects on their mRNA levels. By synthesizing a SINEUP targeting Gdnf mRNA, we were able to increase endogenous GDNF protein levels by about 2-fold. Adeno-associated virus (AAV)9-mediated delivery in the striatum of wild-type (WT) mice led to an increase of endogenous GDNF protein for at least 6 months and the potentiation of the DA system’s functions while showing no side effects. Furthermore, SINEUP-GDNF was able to ameliorate motor deficits and neurodegeneration of DA neurons in a PD neurochemical mouse model. Our data indicate that SINEUP-GDNF could represent a new strategy to increase endogenous GDNF protein levels in a more physiological manner for therapeutic treatments of PD.

Histological placenta features influencing fetal growth and infant anthropometry

During pregnancy, there is a progressive increase in the levels of maternal cholesterol, a lipid that is essential for foetal growth and development. This increase can occur in a physiological (MPH) or supraphysiological (MSPH) manner, where MSPH is associated with detrimental effects on the mother and foetus, including endothelial dysfunction, oxidative stress, and atherosclerosis. Cholesterol is transported from the maternal to the foetal circulation through the placenta by a process that encompasses two main events: cholesterol uptake and efflux. The main receptors and transporters that participate in cholesterol transport are expressed in the human placenta, and their regulation in normal and pathological pregnancies has been evaluated. However, whether elevated levels of cholesterol induce these detrimental changes and whether their expression and function changes in the MSPH condition is still under study, along with the cell types involved in placental cholesterol traffic. Moreover, aside from cholesterol levels, the composition and function of lipoproteins have recently become important to study as these factors may also contribute to the atherogenic process. There is information regarding the maternal and neonatal lipoproteins profile and their changes during pregnancy. However, there are no reports that evaluate the changes of these lipoproteins in MSPH pregnancies. The latter could be relevant considering the consequences that MSPH has on the foetal vasculature. In this review, we summarize the available information regarding cholesterol transport through the placenta and the metabolism of maternal and neonatal lipoproteins in MPH and MSPH conditions, suggesting the importance of increasing our knowledge about these conditions and the monitoring of maternal cholesterol levels during pregnancy.

Progressive dry to humid hyperthermia alters exercise cerebral blood flow

Exercising in hot conditions may increase the risk for exertional heat-related illness due to reduction in cerebral blood flow (CBF); however, the acute effect of exercise-induced changes on CBF during compensable and uncompensable heat stress remain unclear. We tested the hypothesis that exercising in hot dry and humid conditions would have different CBF responses. Nine healthy active males completed a 30 min baseline rest then 60 min of low intensity self-paced exercise (12 rating of perceived exertion) in a 1) control compensable neutral dry (CN; 23.7 ± 0.7 °C; 10.7 ± 0.8%Rh) and 2) compensable hot dry (CH; 42.3 ± 0.3 °C; 10.7 ± 1.8%Rh) that progressively increased to an uncompensable hot humid (UCH; 42.3 ± 0.3 °C; 55.2 ± 7.7%Rh) environment in random order separated by at least 4 days. We observed that during CN environments from rest through 60 min of exercise, middle cerebral velocity (MCAvmean) and conductance (MCAvmean CVC) remained unchanged. In contrast, during CH, MCAvmean, MCAvmean CVC, and cardiac output (Q) increased and systemic vascular resistance (SVR) decreased. However, under UCH, MCAvmean, MCAvmean CVC, and Q was reduced. No difference in mean arterial pressure or ventilation was observed during any condition. Only during UCH, end-tidal PO2 increased and PCO2 decreased. The redistribution of blood to the skin for thermoregulation (heart rate, skin blood flow and sweat rate) remained higher during exercise in UCH environments. Collectively, exercise cerebral blood flow is altered by an integrative physiological manner that differs in CN, CH, and UCH environments. The control of CBF may be secondary to thermoregulatory control which may provide an explanation for the cause of exertional heat illness.

Switchable and Obedient Interfacial Properties That Grant New Biomedical Applications.

Toward imitating the natural smartness and responsivity of biological systems, surface interfacial properties are considered to be responsive and tunable if they show a reactive behavior to an environmental stimulus. This is still quite different from many contemporary biomaterials that lack responsiveness to interact with blood and different body tissues in a physiological manner. Meanwhile it is possible to even go one step further from responsiveness to dual-mode switchability and explore "switchable" or "reversible" responses of synthetic materials. We understand "switchable biomaterials" as materials undergoing a stepwise, structural transformation coupled with considerable changes of interfacial and other surface properties as a response to a stimulus. Therewith, a survey on stimuli-induced dynamic changes of charge, wettability, stiffness, topography, porosity, and thickness/swelling is presented here, as potentially powerful new technologies especially for future biomaterial development. Since living cells constantly sense their environment through a variety of surface receptors and other mechanisms, these obedient interfacial properties were particularly discussed regarding their advantageous multifunctionality for protein adsorption and cell adhesion signaling, which may alter in time and with environmental conditions.

Combined Less-invasive Surgical and Endovascular Technique to Minimise Operative Trauma and Treat Excessive Aortoiliac Thrombotic Obliteration with Popliteo-crural Involvement and Acute Limb Ischaemia

This article demonstrates a less-invasive combined surgical and endovascular alternative approach in a case in which an excessive thrombotic formation in the infrarenal aorta caused occlusion of the iliac artery and the ipsilateral crural arteries. A 51-year-old man was admitted to the authors’ hospital with symptomatology of acute lower limb ischaemia. He had undergone endovascular treatment with placement of kissing stents in the common iliac arteries 2 years previously. A CT angiography scan revealed an extensive thrombus formation in the entire infrarenal aorta occluding the distal infrarenal aorta, the iliac artery and the crural arteries. He underwent a hybrid approach, with exposure of only the right common femoral artery and over-the-wire embolectomy of the infrarenal aorta and the iliac artery, and after the restoration of the inflow, an embolectomy of the peripheral vessels was carried out. To cover the residual aortic thrombus and to restore the severe in-stent restenosis of the previously deployed bare stents, three covered balloon-expandable stents were deployed in kissing technique. The patient was discharged on the fourth postoperative day with palpable peripheral pulses. Combined surgical and endovascular techniques minimise the operative trauma and length of hospital stay for the patient, successfully restoring the perfusion in a physiological manner.

GBA haploinsufficiency accelerates alpha-synuclein pathology with altered lipid metabolism in a prodromal model of Parkinson’s disease

Parkinson's disease (PD) is characterized by dopaminergic (DA) cell loss and the accumulation of pathological alpha synuclein (asyn), but its precise pathomechanism remains unclear, and no appropriate animal model has yet been established. Recent studies have shown that a heterozygous mutation of glucocerebrosidase (gba) is one of the most important genetic risk factors in PD. To create mouse model for PD, we crossed asyn Bacterial Artificial Chromosome transgenic mice with gba heterozygous knockout mice. These double-mutant (dm) mice express human asyn in a physiological manner through its native promoter and showed an increase in phosphorylated asyn in the regions vulnerable to PD, such as the olfactory bulb and dorsal motor nucleus of the vagus nerve. Only dm mice showed a significant reduction in DA cells in the substantia nigra pars compacta, suggesting these animals were suitable for a prodromal model of PD. Next, we investigated the in vivo mechanism by which GBA insufficiency accelerates PD pathology, focusing on lipid metabolism. Dm mice showed an increased level of glucosylsphingosine without any noticeable accumulation of glucosylceramide, a direct substrate of GBA. In addition, the overexpression of asyn resulted in decreased GBA activity in mice, while dm mice tended to show an even further decreased level of GBA activity. In conclusion, we created a novel prodromal mouse model to study the disease pathogenesis and develop novel therapeutics for PD and also revealed the mechanism by which heterozygous gba deficiency contributes to PD through abnormal lipid metabolism under conditions of an altered asyn expression in vivo.

Small Molecule-Based Inducible Gene Therapies for Retinal Degeneration.

The eye is an excellent target organ for gene therapy. It is physically isolated, easily accessible, immune-privileged, and postmitotic. Furthermore, potential gene therapies introduced into the eye can be evaluated by noninvasive methods such as fundoscopy, electroretinography, and optical coherence tomography. In the last two decades, great advances have been made in understanding the molecular underpinnings of retinal degenerative diseases. Building upon the development of modern techniques for gene delivery, many gene-based therapies have been effectively used to treat loss-of-function retinal diseases in mice and men. Significant effort has been invested into making gene delivery vehicles more efficient, less toxic, and non-immunogenic. However, one challenge for the treatment of more complex gain-of-function diseases, many of which might be benefited by the regulation of cellular stress-responsive signaling pathways, is the ability to control the strategy in a physiological (conditional) manner. This review is focused on promising retinal gene therapy strategies that rely on small molecule-based conditional regulation and the inherent limitations and challenges of these strategies that need to be addressed prior to their extensiveuse.

Repairing the Brain: Cell Replacement Using Stem Cell-Based Technologies.

Current approaches to cell replacement therapy in Parkinson’s disease are strongly focused on the dopamine system, with the view that restoring dopaminergic inputs in a localized and physiologic manner will provide superior benefits in terms of effect and longevity compared with oral medication. Experience using transplants of fetal tissue containing dopaminergic cell precursors has provided valuable proof that the approach is feasible, and that engrafted cells can survive and function over many years. However, multiple drawbacks and procedural complications are recognized in using fetal cells. Recent strides in stem cell technology now make it possible to overcome some of the barriers associated with fetal tissue. In particular the generation of high numbers of specific cell types, such as dopaminergic neurons, from stem cells means that quality, consistency, activity, and safety can be more thoroughly determined prior to transplantation, thus providing hope for more robust outcomes. These cells are also predicted to provide benefit without leading to the graft-induced dyskinesia that led to morbidity in a subset of individuals who underwent fetal mesencephalic cell and tissue grafting in the 1990s. In thinking about developing such novel therapeutics, the choice of starting material has also expanded, with the availability of multiple human embryonic stem cell lines, as well as the possibilities for producing induced pluripotent cells, or neuronal cells from a patient’s own tissue. In this article, we speculate on how rapidly expanding knowledge and technical possibilities may impact on stem cell-based therapies for cell replacement in Parkinson’s disease over the next two decades.

Whole-Brain Calcium Imaging during Physiological Vestibular Stimulation in Larval Zebrafish

SummaryThe vestibular apparatus provides animals with postural and movement-related information that is essential to adequately execute numerous sensorimotor tasks. In order to activate this sensory system in a physiological manner, one needs to macroscopically rotate or translate the animal’s head, which in turn renders simultaneous neural recordings highly challenging. Here we report on a novel miniaturized, light-sheet microscope that can be dynamically co-rotated with a head-restrained zebrafish larva, enabling controlled vestibular stimulation. The mechanical rigidity of the microscope allows one to perform whole-brain functional imaging with state-of-the-art resolution and signal-to-noise ratio while imposing up to 25° in angular position and 6,000°/s2 in rotational acceleration. We illustrate the potential of this novel setup by producing the first whole-brain response maps to sinusoidal and stepwise vestibular stimulation. The responsive population spans multiple brain areas and displays bilateral symmetry, and its organization is highly stereotypic across individuals. Using Fourier and regression analysis, we identified three major functional clusters that exhibit well-defined phasic and tonic response patterns to vestibular stimulation. Our rotatable light-sheet microscope provides a unique tool for systematically studying vestibular processing in the vertebrate brain and extends the potential of virtual-reality systems to explore complex multisensory and motor integration during simulated 3D navigation.

3032 - The Cell Polarity and Scaffolding Protein, PAR3, Acts as A Tumour Suppressor in Acute Myeloid Leukemia Through Regulation of the Hippo Pathway

A key feature of epithelial cancers is loss of cell polarity. Polarity in epithelial cells is maintained by three complexes, the Par, Scribble, and Crumbs complexes. PAR3, a key component of the Par polarity complex, acts as a tumour suppressor or promoter in a cell and physiological context dependent manner in epithelial cancers. However, the role of PAR3 in hematopoiesis and hematopoietic malignancies is unknown. We utilised different Par3 conditional knockout mouse models in conjunction with an extensive phenotypic labelling regime and flow cytometry to investigate the role of PAR3 in leukemogenesis. We show loss of PAR3 in experimental mice conferred a strong predisposition to acute myeloid leukemia (AML) as evidenced by a significant increase in Granulocyte/Macrophage progenitors (GMP). In line with these results, interrogation of the TCGA data set revealed AML patients with low levels of PARD3 have a significantly worse prognosis. Reverse Phase Protein Array (RPPA) analyses revealed significant up-regulation of the Hippo downstream transcriptional activator, Yes-associated protein (YAP), in experimental animals compared to controls. Immunohistochemistry confirmed RPPA results and showed YAP was significantly up-regulated in the bone marrow of experimental mice compared to controls and coincided with a significant increase in proliferation as indicated by Ki67 staining. PAR3 and YAP predominantly co-localised in the nucleus further implicating PAR3 as an important component of the Hippo pathway. RNAseq in conjunction with PCR arrays are being conducted to reveal other Hippo family members deregulated in experimental mice compared to controls and we are using 7-color multiplex immunohistochemistry to identify alterations in the spatial distribution and physiology of GMP in the bone marrow upon loss of PAR3. Collectively, our studies will enhance our understanding of how PAR3 suppresses AML and may reveal potential therapeutic targets.

Synthesis and structural characterisation of copper complexes containing methylthiophene and methylfuryl derivatives of (R,R)-1,2-diaminocyclohexane as precatalysts for polymerisation of rac-lactide

A series of Cu(II) complexes supported by methylthiophenyl- and methylfuryl-based (R,R)-1,2-diaminocyclohexane frameworks were synthesised. The synthesised complexes were characterised using infrared spectroscopy, elemental analysis, and single-crystal X-ray diffraction studies. The isopropoxide derivatives of the complexes were employed in the ring-opening polymerisation (ROP) of rac-lactide (rac-LA), yielding polylactides with high number-averaged molecular weight. The catalytic species in this study effectively mediated the stereoselective ROP of rac-LA in a physiological manner (Pr up to 0.92 at room temperature), with ROP activity being mainly dependent on steric hindrance and geometric constraints imposed by methyl substituents attached to the methylthiophenyl and methylfuryl ligands.

Efficiency of Er:YAG utilization in accelerating deep bite orthodontic treatment.

The long duration of orthodontic treatment is a major patients' concern. A noninvasive method of accelerating tooth movement in a physiological manner is needed. The aim of the study was to evaluate the effects of Er:YAG laser application during orthodontic treatment of deep bite and to evaluate its analgesic effect during that movement. A prospective randomized controlled clinical trial (RCT) was performed on 30 patients with deep bite. Sample was divided into two groups: (A), 15 patients (orthodontic treatment-control group) and (B), 15 patients (orthodontic treatment and Er:YAG Laser - laser group). The tooth movement was evaluated as the primary outcome variable by measuring angular and linear changes on three progress lateral cephalometeric radiographs (T1, T2 and T3); Lateral cephalograms were taken before treatment (T1), immediately after finishing the stage of leveling and alignment (T2) and after completion of the intrusion stage (T3).Laser parameters were 400 mJ/10 Hz/4 W and 400 mJ/15 Hz/6 W, depending on the handpiece used. The levels of pain and discomfort were evaluated and ranked according to a visual analog scale. Paired t-tests or Wilcoxon matched-pairs signed-rank tests were used to detect significant differences. The main findings of the treatment were (1) significant positive difference in the rates of tooth intrusion movement on the experimental group compared with the control group at the baseline to T2 and T3 interval and the tooth movement rate was approximately 3 times faster in the experimental group. (2) The pain score in the experimental group was significantly lower compared with the control group on day 3 as on day 7. The application of Er:YAG laser is an effective mean to speed orthodontic tooth movement with a significant reduction in pain and discomfort after application.

Evaluating the Remote Control of Programmed Cell Death, with or without a Compensatory Cell Proliferation.

Organisms and their different component levels, whether organelle, cellular or other, come by birth and go by death, and the deaths are often balanced by new births. Evolution on the one hand has built demise program(s) in cells of organisms but on the other hand has established external controls on the program(s). For instance, evolution has established death program(s) in animal cells so that the cells can, when it is needed, commit apoptosis or senescent death (SD) in physiological situations and stress-induced cell death (SICD) in pathological situations. However, these programmed cell deaths are not predominantly regulated by the cells that do the dying but, instead, are controlled externally and remotely by the cells' superior(s), i.e. their host tissue or organ or even the animal's body. Currently, it is still unclear whether a cell has only one death program or has several programs respectively controlling SD, apoptosis and SICD. In animals, apoptosis exterminates, in a physiological manner, healthy but no-longer needed cells to avoid cell redundancy, whereas suicidal SD and SICD, like homicidal necrosis, terminate ill but useful cells, which may be followed by regeneration of the live cells and by scar formation to heal the damaged organ or tissue. Therefore, “who dies” clearly differentiates apoptosis from SD, SICD and necrosis. In animals, apoptosis can occur only in those cell types that retain a lifelong ability of proliferation and never occurs in those cell types that can no longer replicate in adulthood. In cancer cells, SICD is strengthened, apoptosis is dramatically weakened while SD has been lost. Most published studies professed to be about apoptosis are actually about SICD, which has four basic and well-articulated pathways involving caspases or involving pathological alterations in the mitochondria, endoplasmic reticula, or lysosomes.

A novel three-dimensional cell culture method enhances antiviral drug screening in primary human cells

Gefitinib is a specific inhibitor of the epidermal growth factor receptor (EGFR) and FDA approved for treatment of non-small cell lung cancer. In a previous study we could show the in vitro efficacy of gefitinib for treatment of poxvirus infections in monolayer (2D) cultivated cell lines. Permanent cell lines and 2D cultures, however, are known to be rather unphysiological; therefore it is difficult to predict whether determined effective concentrations or the drug efficacy per se are transferable to the in vivo situation. 3D cell cultures, which meanwhile are widely distributed across all fields of research, are a promising tool for more predictive in vitro investigations of antiviral compounds. In this study the spreading of cowpox virus and the antiviral efficacy of gefitinib were analyzed in primary human keratinocytes (NHEK) grown in a novel 3D extracellular matrix-based cell culture model and compared to the respective monolayer culture. 3D-cultivated NHEK grew in a polarized and thus a more physiological manner with altered morphology and close cell–cell contact. Infected cultures showed a strongly elevated sensitivity towards gefitinib. EGFR phosphorylation, cell proliferation, and virus replication were significantly reduced in 3D cultures at gefitinib concentrations which were at least 100-fold lower than those in monolayer cultures and well below the level of cytotoxicity. Our newly established 3D cell culture model with primary human cells is an easy-to-handle alternative to conventional monolayer cell cultures and previously described more complex 3D cell culture systems. It can easily be adapted to other cell types and a broad spectrum of viruses for antiviral drug screening and many other aspects of virus research under more in vivo-like conditions. In consequence, it may contribute to a more targeted realization of necessary in vivo experiments.

Formation of Human Colonic Crypt Array by Application of Chemical Gradients Across a Shaped Epithelial Monolayer.

Background & AimsThe successful culture of intestinal organoids has greatly enhanced our understanding of intestinal stem cell physiology and enabled the generation of novel intestinal disease models. Although of tremendous value, intestinal organoid culture systems have not yet fully recapitulated the anatomy or physiology of the in vivo intestinal epithelium. The aim of this work was to re-create an intestinal epithelium with a high density of polarized crypts that respond in a physiologic manner to addition of growth factors, metabolites, or cytokines to the basal or luminal tissue surface as occurs in vivo.MethodsA self-renewing monolayer of human intestinal epithelium was cultured on a collagen scaffold microfabricated with an array of crypt-like invaginations. Placement of chemical factors in either the fluid reservoir below or above the cell-covered scaffolding created a gradient of that chemical across the growing epithelial tissue possessing the in vitro crypt structures. Crypt polarization (size of the stem/proliferative and differentiated cell zones) was assessed in response to gradients of growth factors, cytokines, and bacterial metabolites.ResultsChemical gradients applied to the shaped human epithelium re-created the stem/proliferative and differentiated cell zones of the in vivo intestine. Short-chain fatty acids applied as a gradient from the luminal side confirmed long-standing hypotheses that butyrate diminished stem/progenitor cell proliferation and promoted differentiation into absorptive colonocytes. A gradient of interferon-γ and tumor necrosis factor-α significantly suppressed the stem/progenitor cell proliferation, altering crypt formation.ConclusionsThe in vitro human colon crypt array accurately mimicked the architecture, luminal accessibility, tissue polarity, cell migration, and cellular responses of in vivo intestinal crypts.

Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice.

The production of erythropoietin (EPO) by the kidneys, a principal hormone for the hematopoietic system, is reduced in patients with chronic kidney disease (CKD), eventually resulting in severe anemia. Although recombinant human EPO treatment improves anemia in patients with CKD, returning to full red blood cell production without fluctuations does not always occur. We established a method to generate EPO-producing cells from human induced pluripotent stem cells (hiPSCs) by modifying previously reported hepatic differentiation protocols. These cells showed increased EPO expression and secretion in response to low oxygen conditions, prolyl hydroxylase domain-containing enzyme inhibitors, and insulin-like growth factor 1. The EPO protein secreted from hiPSC-derived EPO-producing (hiPSC-EPO) cells induced the erythropoietic differentiation of human umbilical cord blood progenitor cells in vitro. Furthermore, transplantation of hiPSC-EPO cells into mice with CKD induced by adenine treatment improved renal anemia. Thus, hiPSC-EPO cells may be a useful tool for clarifying the mechanisms of EPO production and may be useful as a therapeutic strategy for treating renal anemia.

Influence of Platelet Rich Plasma on Orthodontic Tooth Movement: A Review

Introduction Since the inception of the practice of orthodontics, one of the domain in the research has been the tooth movement and associated biological reaction. Research has been done to study various approaches to achieve tooth movement with most physiological manner but with maximum pace. Th

Advanced Biotechnologies Toward Engineering a Cell Home for Stem Cell Accommodation

AbstractBiomaterials that exhibit bioinspired behavior enable a range of novel biomedical applications. Cell‐friendly biomaterials incorporating crucial physicochemical cues can instruct and dictate cell behavior both in vitro and in vivo. Despite substantial advances, engineering a complex cell regulatory system that incorporates mechanical and chemical signals targeting specific intracellular events has remained far from a reality. Recently, biological studies have begun to decipher the dynamic interplay between stem cells and their microenvironments. Moreover, the myriad recently developed advanced material biotechnologies, such as 3D bioprinting, protein engineering, release technology, high‐throughput screening, and microfluidics, have enabled the engineering of sophisticated biomaterial systems that increasingly closely mimic the spatial and temporal characteristics of the native cell milieu. Thus, biomaterials engineered in the laboratory not only provide a fertile environment for fostering stem cells but also exhibit properties that elicit favorable crosstalk between the structural components, the cells and the host tissue in a precise physiological manner, enabling balanced matrix generation and degradation for successful tissue regeneration to be achieved. This progress report discusses these advanced biotechnologies for the design, fabrication, and functionalization of biomaterials, highlighting their merits over traditional methodologies for mimicking the structural and mechanical properties of their natural in vivo counterparts.