Polyaniline (PANi), a conductive polymer, was blended with a natural protein, gelatin, and co-electrospun into nanofibers to investigate the potential application of such a blend as conductive ...scaffold for tissue engineering purposes. Electrospun PANi–contained gelatin fibers were characterized using scanning electron microscopy (SEM), electrical conductivity measurement, mechanical tensile testing, and differential scanning calorimetry (DSC). SEM analysis of the blend fibers containing less than 3% PANi in total weight, revealed uniform fibers with no evidence for phase segregation, as also confirmed by DSC. Our data indicate that with increasing the amount of PANi (from 0 to ∼5%
w/w), the average fiber size was reduced from 803±121
nm to 61±13
nm (
p
<
0.0
1
) and the tensile modulus increased from 499±207
MPa to 1384±105
MPa (
p
<
0.0
5
). The results of the DSC study further strengthen our notion that the doping of gelatin with a few % PANi leads to an alteration of the physicochemical properties of gelatin. To test the usefulness of PANi-gelatin blends as a fibrous matrix for supporting cell growth, H9c2 rat cardiac myoblast cells were cultured on fiber-coated glass cover slips. Cell cultures were evaluated in terms of cell proliferation and morphology. Our results indicate that all PANi-gelatin blend fibers supported H9c2 cell attachment and proliferation to a similar degree as the control tissue culture-treated plastic (TCP) and smooth glass substrates. Depending on the concentrations of PANi, the cells initially displayed different morphologies on the fibrous substrates, but after 1week all cultures reached confluence of similar densities and morphology. Taken together these results suggest that PANi-gelatin blend nanofibers might provide a novel conductive material well suited as biocompatible scaffolds for tissue engineering.
The demand for biomaterials that promote the repair, replacement, or restoration of hard and soft tissues continues to grow as the population ages. Traditionally, smart biomaterials have been thought ...as those that respond to stimuli. However, the continuous evolution of the field warrants a fresh look at the concept of smartness of biomaterials. This review presents a redefinition of the term "Smart Biomaterial" and discusses recent advances in and applications of smart biomaterials for hard tissue restoration and regeneration. To clarify the use of the term "smart biomaterials", we propose four degrees of smartness according to the level of interaction of the biomaterials with the bio-environment and the biological/cellular responses they elicit, defining these materials as inert, active, responsive, and autonomous. Then, we present an up-to-date survey of applications of smart biomaterials for hard tissues, based on the materials' responses (external and internal stimuli) and their use as immune-modulatory biomaterials. Finally, we discuss the limitations and obstacles to the translation from basic research (bench) to clinical utilization that is required for the development of clinically relevant applications of these technologies.
After nearly seven decades of development, dental composite restorations continue to show limited clinical service. The triggering point for restoration failure is the degradation of the bond at the ...tooth-biomaterial interface from chemical, biological, and mechanical sources. Oral biofilms form at the bonded interfaces, producing enzymes and acids that demineralize hard tissues and damage the composite. Removing bacteria from bonded interfaces and remineralizing marginal gaps will increase restorations' clinical service. To address this need, we propose for the first time the use of piezoelectric nanoparticles of barium titanate (BaTiO
) as a multifunctional bioactive filler in dental resin composites, offering combined antibacterial and (re)mineralization effects. In this work, we developed and characterized the properties of dental piezoelectric resin composites, including the degree of conversion and mechanical and physical properties, for restorative applications. Moreover, we evaluated the antibacterial and mineralization responses of piezoelectric composites
. We observed a significant reduction in biofilm growth (up to 90%) and the formation of thick and dense layers of calcium phosphate minerals in piezoelectric composites compared to control groups. The antibacterial mechanism was also revealed. Additionally, we developed a unique approach evaluating the bond strength of dentin-adhesive-composite interfaces subjected to simultaneous attacks from bacteria and cyclic mechanical loading operating in synergy. Our innovative bioactive multifunctional composite provides an ideal technology for restorative applications using a single filler with combined long-lasting nonrechargeable antibacterial/remineralization effects.
An organoid is a 3D organization of cells that can recapitulate some of the structure and function of native tissue. Recent work has seen organoids gain prominence as a valuable model for studying ...tissue development, drug discovery, and potential clinical applications. The requirements for the successful culture of organoids in vitro differ significantly from those of traditional monolayer cell cultures. The generation and maturation of high-fidelity organoids entails developing and optimizing environmental conditions to provide the optimal cues for growth and 3D maturation, such as oxygenation, mechanical and fluidic activation, nutrition gradients, etc. To this end, we discuss the four main categories of bioreactors used for organoid culture: stirred bioreactors (SBR), microfluidic bioreactors (MFB), rotating wall vessels (RWV), and electrically stimulating (ES) bioreactors. We aim to lay out the state-of-the-art of both commercial and in-house developed bioreactor systems, their benefits to the culture of organoids derived from various cells and tissues, and the limitations of bioreactor technology, including sterilization, accessibility, and suitability and ease of use for long-term culture. Finally, we discuss future directions for improvements to existing bioreactor technology and how they may be used to enhance organoid culture for specific applications.
Snake venoms are attractive natural sources for drug discovery and development, with a number of substances either in clinical use or in research and development. These drugs were developed based on ...RGD-containing snake venom disintegrins, which efficiently antagonize fibrinogen activation of αIIbβ3 integrin (glycoprotein GP IIb/IIIa). Typical examples of anti-platelet drugs found in clinics are Integrilin (Eptifibatide), a heptapeptide derived from Barbourin, a protein found in the venom of the American Southeastern pygmy rattlesnake and Aggrastat (Tirofiban), a small molecule based on the structure of Echistatin, and a protein found in the venom of the saw-scaled viper. Using a similar drug discovery approach, linear and cyclic peptides containing the sequence K(R)TS derived from VP12, a C-type lectin protein found in the venom of Israeli viper venom, were used as a template to synthesize Vipegitide, a novel peptidomimetic antagonist of α2β1 integrin, with anti-platelet activity. This review focus on drug discovery of these anti-platelet agents, their indications for clinical use in acute coronary syndromes and percutaneous coronary intervention based on several clinical trials, as well as their adverse effects.
Abstract Multifunctional bone scaffold materials have been produced from a biodegradable polymer, poly( l -lactic acid) (PLLA), and 1–10% wt of octadecylamine-functionalized nanodiamond (ND-ODA) via ...solution casting followed by compression molding. By comparison to pure PLLA, the addition of 10% wt of ND-ODA resulted in a significant improvement of the mechanical properties of the composite matrix, including a 280% increase in the strain at failure and a 310% increase in fracture energy in tensile tests. The biomimetic process of bonelike apatite growth on the ND-ODA/PLLA scaffolds was studied using microscopic and spectroscopic techniques. The enhanced mechanical properties and the increased mineralization capability with higher ND-ODA concentration suggest that these biodegradable composites may potentially be useful for a variety of biomedical applications, including scaffolds for orthopedic regenerative engineering.
Objectives
Topographic cues can modulate morphology and differentiation of mesenchymal stem cells. This study aimed to determine how topographic cues of a novel bilayered poly (lactic‐co‐glycolic ...acid) (PLGA) scaffold affect osteogenic/odontogenic differentiation of dental pulp stem cells (DPSCs).
Methods
The surface morphology of the scaffolds was visualized by scanning electron microscope, and the surface roughness was measured by profilometry. DPSCs were cultured on each side of the scaffolds. Cell morphology, expression of Yes‐associated protein (YAP) and osteogenic/odontogenic differentiation were analysed by immunohistochemistry, real‐time polymerase chain reaction, and Alizarin Red S staining. In addition, cytochalasin D (CytoD), an F‐actin disruptor, was used to examine the effects of F‐actin on intracellular YAP localisation. Verteporfin, a YAP transcriptional inhibitor, was used to explore the effects of YAP signalling on osteogenic/odontogenic differentiation of DPSCs.
Results
The closed side of our scaffold showed smaller pores and less roughness than the open side. On the closed side, DPSCs exhibited enhanced F‐actin stress fibre alignment, larger spreading area, more elongated appearance, predominant nuclear YAP localization and spontaneous osteogenic differentiation. Inhibition of F‐actin alignments was correlated with nuclear YAP exclusion of DPSCs. Verteporfin restricted YAP localisation to the cytoplasm, down‐regulated expression of early osteogenic/odontogenic markers and inhibited mineralization of DPSCs cultures.
Conclusions
The surface topographic cues changed F‐actin alignment and morphology of DPSCs, which in turn regulated YAP signalling to control osteogenic/odontogenic differentiation.
Snake venoms could lead to the development of new drugs to treat a range of life-threatening conditions like cardiovascular diseases. Most snake venoms contain a large variety of lethal toxins as ...well as anti-adhesive proteins such as disintegrins, which have evolved from the harmless compounds ADAMs (proteins with a disintegrin and a metalloprotease domain) and C-type lectin proteins which disturb connective tissue and cell-matrix interaction. These anti-adhesive proteins target and block integrin receptors and disrupt normal biological processes in snakes' prey such as connective tissue physiology and blood clotting. This chapter provides the experimental details of a practical, cell-based adhesion protocol to help identify and isolate disintegrins and C-type lectin proteins from snake venoms, important tools in integrin research and lead compounds for drug discovery.
Microgravity is known to impact bone health, similar to mechanical unloading on Earth. In the absence of countermeasures, bone formation and mineral deposition are strongly inhibited in Space. There ...is an unmet need to identify nutritional countermeasures. Curcumin and carnosic acid are phytonutrients with anticancer, anti-inflammatory, and antioxidative effects and may exhibit osteogenic properties. Zinc is a trace element essential for bone formation. We hypothesized that these nutraceuticals could counteract the microgravity-induced inhibition of osteogenic differentiation and function. To test this hypothesis, we cultured 7F2 murine osteoblasts in simulated microgravity (SMG) in a Random Positioning Machine in the presence and absence of curcumin, carnosic acid, and zinc and evaluated cell proliferation, function, and differentiation. SMG enhanced cell proliferation in osteogenic medium. The nutraceuticals partially reversed the inhibitory effects of SMG on alkaline phosphatase (ALP) activity and did not alter the SMG-induced reduction in the expression of osteogenic marker genes in osteogenic medium, while they promoted osteoblast proliferation and ALP activity in the absence of traditional osteogenic media. We further observed a synergistic effect of the intermix of the phytonutrients on ALP activity. Intermixes of phytonutrients may serve as convenient and effective nutritional countermeasures against bone loss in space.
PDF
