A post-classical theory of enamel biomineralization… and why we need one

Enamel crystals are unique in shape, orientation and organization. They are hundreds of thousands times longer than they are wide, run parallel to each other, are oriented with respect to the ameloblast membrane at the mineralization front and are organized into rod or interrod enamel. The classical theory of amelogenesis postulates that extracellular matrix proteins shape crystallites by specifically inhibiting ion deposition on the crystal sides, orient them by binding multiple crystallites and establish higher levels of crystal organization. Elements of the classical theory are supported in principle by in vitro studies; however, the classical theory does not explain how enamel forms in vivo. In this review, we describe how amelogenesis is highly integrated with ameloblast cell activities and how the shape, orientation and organization of enamel mineral ribbons are established by a mineralization front apparatus along the secretory surface of the ameloblast cell membrane.

Biomimetic delivery of signals for bone tissue engineering

Bone tissue engineering is an exciting approach to directly repair bone defects or engineer bone tissue for transplantation.Biomaterials play a pivotal role in providing a template and extracellular environment to support regenerative cells and promote tissue regeneration. A variety of signaling cues have been identified to regulate cellular activity, tissue development, and the healing process. Numerous studies and trials have shown the promise of tissue engineering, but successful translations of bone tissue engineering research into clinical applications have been limited, due in part to a lack of optimal delivery systems for these signals. Biomedical engineers are therefore highly motivated to develop biomimetic drug delivery systems, which benefit from mimicking signaling molecule release or presentation by the native extracellular matrix during development or the natural healing process. Engineered biomimetic drug delivery systems aim to provide control over the location, timing, and release kinetics of the signal molecules according to the drug's physiochemical properties and specific biological mechanisms. This article reviews biomimetic strategies in signaling delivery for bone tissue engineering, with a focus on delivery systems rather than specific molecules. Both fundamental considerations and specific design strategies are discussed with examples of recent research progress, demonstrating the significance and potential of biomimetic delivery systems for bone tissue engineering.

Control of Emotion and Wakefulness by Neurotensinergic Neurons in the Parabrachial Nucleus

The parabrachial nucleus(PBN)integrates interoceptive and exteroceptive information to control various behavioral and physiological processes including breathing,emotion,and sleep/wake regulation through the neural circuits that connect to the forebrain and the brainstem.However,the precise identity and function of distinct PBN subpopulations are still largely unknown.Here,we leveraged molecular characterization,retrograde tracing,optogenetics,chemogenetics,and electrocortical recording approaches to identify a small subpopulation of neurotensin-expressing neurons in the PBN that largely project to the emotional control regions in the forebrain,rather than the medulla.Their activation induces freezing and anxiety-like behaviors,which in turn result in tachypnea.In addition,optogenetic and chemogenetic manipulations of these neurons revealed their function in promoting wakefulness and maintaining sleep architecture.We propose that these neurons comprise a PBN subpopulation with specific gene expression,connectivity,and function,which play essential roles in behavioral and physiological regulation.

Minimal invasive microscopic tooth preparation in esthetic restoration: a specialist consensus

By removing a part of the structure,the tooth preparation provides restorative space,bonding surface,and finish line for various restorations on abutment.Preparation technique plays critical role in achieving the optimal result of tooth preparation.With successful application of microscope in endodontics for>30 years,there is a full expectation of microscopic dentistry.However,as relatively little progress has been made in the application of microscopic dentistry in prosthodontics,the following assumptions have been proposed:Is it suitable to choose the tooth preparation technique under the naked eye in the microscopic vision?Is there a more accurate preparation technology intended for the microscope?To obtain long-term stable therapeutic effects,is it much easier to achieve maximum tooth preservation and retinal protection and maintain periodontal tissue and oral function health under microscopic vision?Whether the microscopic prosthodontics is a gimmick or a breakthrough in obtaining an ideal tooth preparation should be resolved in microscopic tooth preparation.This article attempts to illustrate the concept,core elements,and indications of microscopic minimally invasive tooth preparation,physiological basis of dental pulp,periodontium and functions involved in tool preparation,position ergonomics and visual basis for dentists,comparison of tooth preparation by naked eyes and a microscope,and comparison of different designs of microscopic minimally invasive tooth preparation techniques.Furthermore,a clinical protocol for microscopic minimally invasive tooth preparation based on target restorative space guide plate has been put forward and new insights on the quantity and shape of microscopic minimally invasive tooth preparation has been provided.

Glucose deprivation induces chemoresistance in colorectal cancer cells by increasing ATF4 expression

AIM: To investigate the role of activating transcription factor 4(ATF4) in glucose deprivation(GD) induced colorectal cancer(CRC) drug resistance and the mechanism involved.METHODS: Chemosensitivity and apoptosis were measured under the GD condition. Inhibition of ATF4 using short hairpin RNA in CRC cells under the GD condition and in ATF4-overexpressing CRC cells was performed to identify the role of ATF4 in the GD induced chemoresistance. Quantitative real-time RTPCR and Western blot were used to detect the mR NA and protein expression of drug resistance gene 1(MDR1), respectively.RESULTS: GD protected CRC cells from drug-induced apoptosis(oxaliplatin and 5-fluorouracil) and induced the expression of ATF4, a key gene of the unfolded protein response. Depletion of ATF4 in CRC cells under the GD condition can induce apoptosis and drug resensitization. Similarly, inhibition of ATF4 in the ATF4-overexpressing CRC cells reintroduced therapeutic sensitivity and apoptosis. In addition, increased MDR1 expression was observed in GD-treated CRC cells. CONCLUSION: These data indicate that GD promotes chemoresistance in CRC cells through up-regulating ATF4 expression.

CHIP regulates bone mass by targeting multiple TRAF family members in bone marrow stromal cells

Carboxyl terminus of Hsp70-interacting protein（CHIP or STUB1） is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that Chip deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. We found that osteoblast differentiation and bone formation were also decreased in Chip KO mice. In bone marrow stromal（BMS） cells derived from Chip^-/- mice, expression of a panel of osteoblast marker genes was significantly decreased. ALP activity and mineralized bone matrix formation were also reduced in Chip-deficient BMS cells. We also found that in addition to the regulation of TRAF6, CHIP also inhibits TNFα-induced NF-κB signaling through promoting TRAF2 and TRAF5 degradation. Specific deletion of Chip in BMS cells downregulated expression of osteoblast marker genes which could be reversed by the addition of NF-κB inhibitor. These results demonstrate that the osteopenic phenotype observed in Chip^-/- mice was due to the combination of increased osteoclast formation and decreased osteoblast differentiation. Taken together, our findings indicate a significant role of CHIP in bone remodeling.

Hybrid polymer biomaterials for bone tissue regeneration

Native tissues possess unparalleled physiochemical and biological functions, which can be attributed to their hybrid polymer composition and intrinsic bioactivity. However, there are also various concerns or limitations over the use of natural materials derived from animals or cadavers, including the potential immunogenicity, pathogen transmission, batch to batch consistence and mismatch in properties for various applications. Therefore, there is an increasing interest in developing degradable hybrid polymer biomaterials with controlled properties for highly efficient biomedical applications. There have been efforts to mimic the extracellular protein structure such as nanofibrous and composite scaffolds, to functionalize scaffold surface for improved cellular interaction, to incorporate controlled biomolecule release capacity to impart biological signaling, and to vary physical properties of scaffolds to regulate cellular behavior. In this review, we highlight the design and synthesis of degradable hybrid polymer biomaterials and focus on recent developments in osteoconductive, elastomeric, photoluminescent and electroactive hybrid polymers. The review further exemplifies their applications for bone tissue regeneration.

Kinetic study of all-or-none hemolysis induced by cationic amphiphilic polymethacrylates with antimicrobial activity

To gain an understanding of the toxicity of antimicrobial polymers to human cells, their hemolytic action was investigated using human red blood cells （RBCs）. We examined the hemolysis induced by cationic amphiphilic methacrylate random copolymers, which have amino ethyl sidechains as cationic units and either butyl or methyl methacpjlate as hydrophobic units. The polymer with 30 tool% butyl sidechains （B3o） displayed higher hemolytic toxicity than the polymer with 59 tool% methyl sidechains （Ms9）. B3o also induced faster release of hemoglobin from RBCs than lVlsg. A new theoretical model is proposed based on two consecutive steps to form active polymer species on the RBC membranes, which are associated to RBC lysis. This model takes the all-or-none release of hemoglobin by the rupture of RBCs into account, providing new insight into the polymer-induced hemolysis regarding how individual or collective ceils respond to the polymers.

Synthetic biodegradable functional polymers for tissue engineering:a brief review

Scaffolds play a crucial role in tissue engineering. Biodegradable polymers with great processing flexibility are the predominant scaffolding materials. Synthetic biodegradable polymers with well-defined structure and without immunological concerns associated with naturally derived polymers are widely used in tissue engineering. The synthetic biodegradable polymers that are widely used in tissue engineering, including polyesters, polyanhydrides, polyphosphazenes, polyurethane, and poly(glycerol sebacate) are summarized in this article. New developments in conducting polymers, photoresponsive polymers, amino-acid-based polymers, enzymatically degradable polymers, and peptide-activated polymers are also discussed. In addition to chemical functionalization, the scaffold designs that mimic the nano and micro features of the extracellular matrix(ECM) are presented as well, and composite and nanocomposite scaffolds are also reviewed.

Functionalized scaffolds to enhance tissue regeneration

Tissue engineering scaffolds play a vital role in regenerative medicine.It not only provides a temporary 3-dimensional support during tissue repair,but also regulates the cell behavior,such as cell adhesion,proliferation and differentiation.In this review,we summarize the development and trends of functional scaffolding biomaterials including electrically conducting hydrogels and nanocomposites of hydroxyapatite(HA)and bioactive glasses(BGs)with various biodegradable polymers.Furthermore,the progress on the fabrication of biomimetic nanofibrous scaffolds from conducting polymers and composites of HA and BG via electrospinning,deposition and thermally induced phase separation is discussed.Moreover,bioactive molecules and surface properties of scaffolds are very important during tissue repair.Bioactive molecule-releasing scaffolds and antimicrobial surface coatings for biomedical implants and scaffolds are also reviewed.