Fatigue behaviour of load-bearing polymeric bone scaffolds: A review.

Bone scaffolds play a crucial role in bone tissue engineering by providing mechanical support for the growth of new tissue while enduring static and fatigue loads. Although polymers possess favourable characteristics such as adjustable degradation rate, tissue-compatible stiffness, ease of fabrication, and low toxicity, their relatively low mechanical strength has limited their use in load-bearing applications. While numerous studies have focused on assessing the static strength of polymeric scaffolds, little research has been conducted on their fatigue properties. The current review presents a comprehensive study on the fatigue behaviour of polymeric bone scaffolds. The fatigue failure in polymeric scaffolds is discussed and the impact of material properties, topological features, loading conditions, and environmental factors are also examined. The present review also provides insight into the fatigue damage evolution within polymeric scaffolds, drawing comparisons to the behaviour observed in natural bone. Additionally, the effect of polymer microstructure, incorporating reinforcing materials, the introduction of topological features, and hydrodynamic/corrosive impact of body fluids in the fatigue life of scaffolds are discussed. Understanding these parameters is crucial for enhancing the fatigue resistance of polymeric scaffolds and holds promise for expanding their application in clinical settings as structural biomaterials. STATEMENT OF SIGNIFICANCE: Polymers have promising advantages for bone tissue engineering, including adjustable degradation rates, compatibility with native bone stiffness, ease of fabrication, and low toxicity. However, their limited mechanical strength has hindered their use in load-bearing scaffolds for clinical applications. While prior studies have addressed static behaviour of polymeric scaffolds, a comprehensive review of their fatigue performance is lacking. This review explores this gap, addressing fatigue characteristics, failure mechanisms, and the influence of parameters like material properties, topological features, loading conditions, and environmental factors. It also examines microstructure, reinforcement materials, pore architectures, body fluids, and tissue ingrowth effects on fatigue behaviour. A significant emphasis is placed on understanding fatigue damage progression in polymeric scaffolds, comparing it to natural bone behaviour.

Recent advances and future directions of 3D to 6D printing in brain cancer treatment and neural tissue engineering.

The field of neural tissue engineering has undergone a revolution due to advancements in three-dimensional (3D) printing technology. This technology now enables the creation of intricate neural tissue constructs with precise geometries, topologies, and mechanical properties. Currently, there are various 3D printing techniques available, such as stereolithography and digital light processing, and a wide range of materials can be utilized, including hydrogels, biopolymers, and synthetic materials. Furthermore, the development of four-dimensional (4D) printing has gained traction, allowing for the fabrication of structures that can change shape over time using techniques such as shape-memory polymers. These innovations have the potential to facilitate neural regeneration, drug screening, disease modeling, and hold tremendous promise for personalized diagnostics, precise therapeutic strategies against brain cancers. This review paper provides a comprehensive overview of the current state-of-the-art techniques and materials for 3D printing in neural tissue engineering and brain cancer. It focuses on the exciting possibilities that lie ahead, including the emerging field of 4D printing. Additionally, the paper discusses the potential applications of five-dimensional and six-dimensional printing, which integrate time and biological functions into the printing process, in the fields of neuroscience.

Investigation and multiscale modeling of PVA/SA coated poly lactic acid scaffold containing curcumin loaded layered double hydroxide nanohybrids.

Applying hydrophilic coatings on polymeric nanofibers combined with layered double hydroxide (LDH) not only enhances the efficiency of drug delivery systems but also increases cell adhesion. This work aimed to prepare poly(vinyl alcohol)/sodium alginate (PVA/SA) (2/1)-coated poly(lactic acid) (PLA) nanofibers containing curcumin-loaded layered double hydroxide (LDH) and to investigate their drug release and mechanical properties and their biocompatibility. The optimum PLA nanofibrous sample was considered to be that based on 3 wt% of curcumin-loaded LDH (PLA-3%LDH) with a drug encapsulation efficiency of ∼18% in which a minimum average nanofiber diameter of ∼476 nm along with a high tensile strength of 3.00 MPa were obtained. In the next step, a PVA/SA (2/1) layer was coated on the PLA-3%LDH; as a result, the hydrophilicity of the sample was improved and the elongation at break was decreased remarkably. In this regard the cell viability reached 80% for the coated PLA. Moreover, the formation of a layer of (PVA/SA) on the PLA nanofibers lowered the burst release and resulted in a more sustained drug release, which is a vital feature in dermal applications. A multiscale modeling method was applied for simulation of the mechanical properties of the composite scaffold and the results showed that this method can predict the data with 83% accuracy. The results of this study indicate that the formation of a layer of PVA/SA (2/1) has a significant effect on hydrophilicity and consequently improves cell adhesion and proliferation.

Fabrication and multiscale modeling of polycaprolactone/amniotic membrane electrospun nanofiber scaffolds for wound healing.

BACKGROUND: Enhancing the efficiency of cell-based skin tissue engineering (TE) approaches is possible via designing electrospun scaffolds possessing natural materials like amniotic membrane (AM) with wound healing characteristics. Concentrating on this aim, we fabricated innovative polycaprolactone (PCL)/AM scaffolds through the electrospinning process. METHODS: The manufactured structures were characterized by employing scanning electron microscope (SEM), attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, tensile testing, Bradford protein assay, etc. In addition, the mechanical properties of scaffolds were simulated by the multiscale modeling method. RESULTS: As a result of conducting various tests, it was concluded that the uniformity and distribution of fibers decreased with an increase in the amniotic content. Furthermore, PCL-AM scaffolds contained amniotic and PCL characteristic bands. In the case of protein release, greater content of AM led to the release of higher amounts of collagen. Tensile testing revealed that scaffolds' ultimate strength increased when the AM content augmented. The multiscale modeling demonstrated that the scaffold had elastoplastic behavior. In order to assess cellular attachment, viability, and differentiation, human adipose-derived stem cells (ASCs) were seeded on the scaffolds. In this regard, SEM and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays showed significant cellular proliferation and viability on the proposed scaffolds, and these analyses illustrated that higher cell survival and adhesion could be achieved when scaffolds possessed a larger amount of AM. After 21 days of cultivation, particular keratinocyte markers, such as keratin I and involucrin, were identified through utilizing immunofluorescence and real-time polymerase chain reaction (PCR) tests. The markers' expressions were higher in the PCL-AM scaffold with a ratio of 90:10 v v-1 compared with the PCL-epidermal growth factor (EGF) structure. Moreover, the presence of AM in the scaffolds resulted in the keratinogenic differentiation of ASCs even without employing EGF. Consequently, this state-of-the-art experiment suggests that the PCL-AM scaffold can be a promising candidate in skin bioengineering. CONCLUSION: This study showed that mixing AM with PCL, a widely used polymer, in different concentrations can overcome PCL disadvantages such as high hydrophobicity and low cellular compatibility.

A novel co-culture assay to evaluate the effects of sympathetic innervation on vascular smooth muscle differentiation.

Dedifferentiation of vascular smooth muscle cells (VSMCs) from a functional phenotype to an inverse synthetic phenotype is a symptom of cardiovascular disorders, such as atherosclerosis and hypertension. The sympathetic nervous system (SNS) is an essential regulator of the differentiation of vascular smooth muscle cells (VSMCs). In addition, numerous studies suggest that SNS also stimulates VSMCs to retain their contractile phenotype. However, the molecular mechanisms for this stimulation have not been thoroughly studied. In this study, we used a novel in vitro co-culture method to evaluate the effective cellular interactions and stimulatory effects of sympathetic neurons on the differentiation of VSMCs. We co-cultured rat neural-like pheochromocytoma cells (PC12) and rat aortic VSMCs with this method. Expression of VSMCs contractile genes, including smooth muscle actin (acta2), myosin heavy chain (myh11), elastin (eln), and smoothelin (smtn), were determined by quantitative real-time-PCR analysis as an indicator of VSMCs differentiation. Fold changes for specific contractile genes in VSMCs grown in vitro for seven days in the presence (innervated) and absence (non-innervated) of sympathetic neurons were 3.5 for acta2, 6.5 for myh11, 4.19 for eln, and 4 for smtn (normalized to Tata Binding Protein (TBP)). As a result, these data suggest that sympathetic innervation promotes VSMCs' contractile gene expression and also maintains VSMCs' functional phenotype.

Surface Modification of an Absorbable Bimodal Fe-Mn-Ag Alloy by Nitrogen Plasma Immersion Ion Implantation.

Recently, Fe-Mn-based alloys have been increasingly catching the attention of the scientific community, because of their tunable and outstanding mechanical properties, and suitable degradation behavior for biomedical applications. In spite of these assets, their corrosion rate (CR) is, in general, too low to satisfy the requirements that need to be met for cardiovascular device applications, such as stents. In fact, the CR is not always the same for all of the degradation stages of the material, and in addition, a finely tuned release rate, especially during the first steps of the corrosion pattern, is often demanded. In this work, a resorbable bimodal multi-phase alloy Fe-3Mn-1Ag was designed by mechanical alloying and spark plasma sintering (SPS) to accelerate the corrosion rate. The presence of several phases, for example α-Fe, α-Mn, γ-FeMn and Ag, provided the material with excellent mechanical properties (tensile strength UTS = 722 MPa, tensile strain A = 38%) and a higher corrosion rate (CR = 3.2 ± 0.2 mm/year). However, higher corrosion rates, associated with an increased release of degradation elements, could also raise toxicity concerns, especially at the beginning of the corrosion pattern. In this study, The focus of the present work was the control of the CR by surface modification, with nitrogen plasma immersion ion implantation (N-PIII) treatment that was applied to mechanically polished (MP) samples. This plasma treatment (PT) improved the corrosion resistance of the material, assessed by static degradation immersion tests (SDITs), especially during the first degradation stages. Twenty-eight days later, the degradation rate reached the same value of the MP condition. Nitrogen compounds on the surface of the substrate played an important role in the corrosion mechanism and corrosion product formation. The degradation analysis was carried out also by potentiodynamic tests in modified Hanks' balanced salt solution (MHBSS), and Dulbecco's phosphate buffered saline solution (DPBSS). The corrosion rate was higher in MHBSS for both conditions. However, there was no significant difference between the corrosion rate of the PT in DPBSS (CR = 1.9 ± 0.6 mm/year) and in MHBSS (CR = 2 ± 1.4 mm/year). The cell viability was assessed with human vein endothelial cells (HUVECs) via an indirect metabolic activity test (MTT assay). Due to the lower ion release of the PT condition, the cell viability increased significantly. Thus, nitrogen implantation can control the in vitro corrosion rate starting from the very first stage of the implantation, improving cell viability.

The effect of Nano-liposomal sodium nitrite on smooth muscle cell growth in a tissue-engineered small-diameter vascular graft.

BACKGROUND: Nitric oxide is a chemical agent produced by endothelial cells in a healthy blood vessel, inhibiting the overgrowth of vascular smooth muscle cells and regulating vessel tone. Liposomes are biocompatible and biodegradable drug carriers with a similar structure to cell bilayer phospholipid membrane that can be used as useful nitric oxide carriers in vascular grafts. METHOD: Using a custom-designed apparatus, the sheep carotid arteries were decellularized while still maintaining important components of the vascular extracellular matrix (ECM), allowing them to be used as small-diameter vascular grafts. A chemical signal of sodium nitrite was applied to control smooth muscle cells' behavior under static and dynamic cell culture conditions. The thin film hydration approach was used to create nano-liposomes, which were then used as sodium nitrite carriers to control the drug release rate and enhance the amount of drug loaded into the liposomes. RESULTS: The ratio of 80:20:2 for DPPC: Cholesterol: PEG was determined as the optimum formulation of the liposome structure with high drug encapsulation efficiency (98%) and optimum drug release rate (the drug release rate was 40%, 65%, and 83% after 24, 48, and 72 h, respectively). MTT assay results showed an improvement in endothelial cell proliferation in the presence of nano-liposomal sodium nitrite (LNS) at the concentration of 0.5 µg/mL. Using a suitable concentration of liposomal sodium nitrite (0.5 µg/mL) put onto the constructed scaffold resulted in the controllable development of smooth muscle cells in the experiment. The culture of smooth muscle cells in a pulsatile perfusion bioreactor indicated that in the presence of synthesized liposomal sodium nitrite, the overgrowth of smooth muscle cells was inhibited in dynamic cell culture conditions. The mechanical properties of ECM graft were measured, and a multi-scale model with an accuracy of 83% was proposed to predict mechanical properties successfully. CONCLUSION: The liposomal drug-loaded small-diameter vascular graft can prevent the overgrowth of SMCs and the formation of intimal hyperplasia in the graft. Aside from that, the effect of LNS on endothelial has the potential to stimulate endothelial cell proliferation and re-endothelialization.

Investigation of electrical stimulation on phenotypic vascular smooth muscle cells differentiation in tissue-engineered small-diameter vascular graft.

In the development of vascular tissue engineering, particularly in the case of small diameter vessels, one of the key obstacles is the blockage of these veins once they enter the in vivo environment. One of the contributing factors to this problem is the aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) from the media layer of the artery to the interior of the channel. Two distinct phenotypes have been identified for smooth muscle cells, namely synthetic and contractile. Since the synthetic phenotype plays an essential role in the unusual growth and migration, the aim of this study was to convert the synthetic phenotype into the contractile one, which is a solution to prevent the abnormal growth of VSMCs. To achieve this goal, these cells were subjected to electrical signals, using a 1000 µA sinusoidal stimulation at 10 Hz for four days, with 20 min duration per 24 h. The morphological transformations and changes in the expression of vimentin, nestin, and ß-actin proteins were then studied using ICC and flow cytometry assays. Also, the expression of VSMC specific markers such as smooth muscle myosin heavy chain (SMMHC) and smooth muscle alpha-actin (α-SMA) were evaluated using RT-PCR test. In the final phase of this study, the sheep decellularized vessel was employed as a scaffold for seeding these cells. Based on the results, electrical stimulation resulted in some morphological alterations in VSMCs. Furthermore, the observed reductions in the expression levels of vimentin, nestin and ß-actin proteins and increase in the expression of SMMHC and α-SMA markers showed that it is possible to convert the synthetic phenotype to the contractile one using the studied regime of electrical stimulation. Finally, it can be concluded that electrical stimulation can significantly affect the phenotype of VSMCs, as demonstrated in this study.

Experimental investigation and finite element modelling of PMMA/carbon nanotube nanobiocomposites for bone cement applications.

Multi-walled carbon nanotubes (MWCNTs) are one of the preferred candidates for reinforcing polymeric nanobiocomposites, such as acrylic bone type of cement. In this study, at first, bulk samples of the reinforced polymethylmethacrylate (PMMA) matrix were prepared with 0.1, 0.25, and 0.5 wt per wt% of MWCNTs by the casting method. Tensile and three-point bending tests were performed to determine the essential mechanical properties of bone cement, such as tensile and bending strengths. The tensile fracture surfaces were investigated by scanning electron microscopy (SEM). The commercial software (Abaqus) was used to conduct finite element analysis (FEA) by constructing a representative volume element (RVE) model for numerically computing the tensile and bending parameters of PMMA-MWCNT nanocomposites. Finally, MTT assays were utilized to evaluate the cell viability on the surface of nanobiocomposites. The results show that by increasing the MWCNT amount in the PMMA-based cement, the bending strengths (BS), tensile strength (TS), and elastic modulus (EM) increased considerably. Furthermore, the disparity between the FEA and experimental TS, EM, and BS values was less than 20%. According to MTT viability experiments, adding MWCNTs to PMMA had no influence on PMMA toxicity and resulted in a negative response to interaction with mesenchymal stem cells. The cell density on the nanobiocomposite was more than pristine-PMMA.

Medical application of biomimetic 4D printing.

Additive manufacturing has attracted a lot of attention in fabrication of bio medical devices and structures in recent years. 4D printing, a new class of 3D printing where time is considered as a 4th dimension, allows us to build biological structures such as scaffolds, implants, and stents with dynamic performance mimicking the body's natural tissues. In order to properly exploit the capabilities of this fabrication method, understanding and exploiting the shape memory materials is critical. These 'smart' materials are responsive to the external stimuli which eliminates the need for utilizing the sensors, and batteries. These stimuli-triggered 'smart' materials possess a dynamic behavior unlike the static scaffolds based on conventional manufacturing techniques. In this review, recent advances on application of 4D printing for manufacturing of this type of materials and other high-performance biomaterials for medical applications have been discussed.

In Vitro Degradation, Hemocompatibility, and Cytocompatibility of Nanostructured Absorbable Fe-Mn-Ag Alloys for Biomedical Application.

The addition of noble elements such as Ag was shown as a successful method to accelerate the corrosion rate of absorbable Fe-based alloys. One major concern of Ag addition is its effect on hemocompatibility and biocompatibility. In this study, in vitro degradation and surface analysis of Fe-30Mn-xAg (x = 0, 1, and 3 wt %) alloys as well as their effects on hemocompatibility and cell viability of human umbilical vein endothelial cells (HUVECs) were investigated. The static degradation rate of the alloys was 4.97, 4.69, and 4.49 mg/cm2 for Fe-30Mn, Fe-30Mn-1Ag, and Fe-30Mn-3Ag, respectively. The surface analysis after degradation showed that γ-FeOOH was formed on Fe-30Mn-3Ag, while α-FeOOH was more dominant on Fe-30Mn and Fe-30Mn-1Ag. As γ-FeOOH is more soluble than α-FeOOH, it assists further degradation of Fe-30Mn-3Ag alloy. The high amount of Ag, which induced the hemolysis ratio, however, inhibited coagulation by decreasing the platelet adhesion. Fe-30Mn-1Ag and Fe-30Mn-3Ag alloys show an improved cell viability as compared to that of Fe-Mn alloy. Shear yield strength and shear elastic modulus of the samples after immersion tests were increased, while the ultimate shear strength was not affected. On the basis of the acceptable hemolysis rate, low platelet adhesion, acceptable cell viability, and appropriate mechanical properties after degradation, Fe-30Mn-1Ag can be considered as a suitable blood-contacting Fe-based absorbable alloy.

Preclinical studies of acellular extracellular matrices as small-caliber vascular grafts.

Due to morbidity and mortality of cardiovascular diseases around the globe, there has been an unmet clinical need for small caliber vascular grafts. Autologous vessels are still the gold standard for small caliber vascular grafts (<6 mm). In an attempt to develop a tissue-engineered vascular graft, several approaches have been pursued. One of the promising techniques is the use of acellular matrices offering a prospect of being able to meet the demand for small caliber vessels. Acellular matrices can ideally preserve the vascular wall complexity, biochemical properties, and bioactivity required for tissue regeneration and function. Various strategies have emerged to increase long term patency of acellular matrices including surface modification and pre-implantation cell seeding. This article reviews the most recent and relevant in vivo studies on acellular small caliber vascular grafts, which provides an outlook toward the preclinical potential of acellular extracellular matrices in vascular tissue engineering.

Synthesis and characterization of Zn/Al-LDH@SiO2 nanohybrid: Intercalation and release behavior of vitamin C.

Layered double hydroxide (LDH) nanoparticles (NPs) have potential applications for the loading and controlled release of drugs. This study investigated the synthesis of Zn/Al-LDH using the co-precipitation and ion-exchange methods, coating with SiO2 NPs and precise control of the release of vitamin C (VC). The results showed that more VC could be loaded by ion exchange. The surface of the VC-loaded LDH NPs was coated with SiO2 using the sol-gel and physical mixing methods. The structure, surface morphology, drug loading and thermostability were characterized and the drug release profile and release kinetics of the intercalated LDHs were studied. It was found that the SiO2 NPs more uniformly coated the LDH surfaces using the sol-gel process than the physical mixing method. The release behavior of VC from the intercalated nanohybrid is well described by the Avrami-Erofe'ev and Elovich models in the slow and fast stages. The sol-gel coated LDH@SiO2 nanohybrid system showed sustained drug delivery compared to the physical mixing method. The overall VC release from LDH increased more than 3-fold after coating with SiO2 NPs. Taken together, the Zn/Al-LDH@SiO2 coated by sol-gel should be considered as a potential sustained-release drug delivery system for VC.

A biomaterials approach to Schwann cell development in neural tissue engineering.

Schwann cells, in addition to forming myelin sheaths, have pivotal roles in regeneration of injured axons in the peripheral nervous system such as producing a natural permissive conduit between distal and proximal stumps and secreting nerve growth factors. Due to the atrophy and senescence of Schwann cells in long nerve gap, and the need to ensure the presence of nerve growth factors and basal lamina tubes for axon regeneration in a critical time, injection of Schwann cells with the aid of an engineered conduit seems to be an effective approach to induce axon regrowth. Stem cells with high differentiation and proliferation capability can provide an adequate number of Schwann cells in healthy state for regeneration purposes. Guidance of stem cells differentiation into desired lineages, control of implanted Schwann cells fate, maintenance of nerve growth factors expression, and guidance of axon regrowth are possible with the aid of biomaterials with appropriate chemical, physical, and mechanical properties. Biomaterials' surface chemistry and biomolecules interacting with cells' receptors initiate specific intracellular signaling cascades and direct cells fate. In addition, biomaterials' surface topography in association with cells contact area, focal adhesion, and cytoskeletal remodeling by mechanotransduction process influences cells behavior and induces specific differentiation. The main objective of this review is to investigate the chemical, topographical, and mechanical properties of biomaterials which influence the fate of Schwann cells and the nerve regeneration process.

Carboxymethyl kappa carrageenan-modified decellularized small-diameter vascular grafts improving thromboresistance properties.

The development of decellularized small-diameter vascular grafts is a potential solution for patients requiring vascular reconstructive procedures. However, there is a limitation for acellular scaffolds due to incomplete recellularization and exposure of extracellular matrix components to whole blood resulting in platelet adhesion. To address this issue, a perfusion decellularization method was developed using a custom-designed set up which completely removed cell nuclei and preserved three-dimensional structure and mechanical properties of native tissue (sheep carotid arteries). Afterwards, carboxymethyl kappa carrageenan (CKC) was introduced as a novel anticoagulant in vascular tissue engineering which can inhibit thrombosis formation. The method enabled uniform immobilization of CKC on decellularized arteries as a result of interaction between amine functional groups of decellularized arteries and carboxyl groups of CKC. The CKC modified graft significantly reduced platelet adhesion from 44.53 ± 2.05% (control) to 19.57 ± 1.37% (modified) and supported endothelial cells viability, proliferation, and nitric oxide production. Overall, the novel CKC modified scaffold provides a promising solution for thrombosis formation of small-diameter vessels and could be a potent graft for future in vivo applications in vascular bypass procedures. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1690-1701, 2019.

Comparative analysis and properties evaluation of gelatin microspheres crosslinked with glutaraldehyde and 3-glycidoxypropyltrimethoxysilane as drug delivery systems for the antibiotic vancomycin.

In the present comparative study, gelatin microspheres (GMs) were prepared by emulsification-solvent-extraction method using well-known crosslinker: glutaraldehyde (GA) and biocompatible silane-coupling agent: glycidoxypropyltrimethoxysilane (GPTMS). Crosslinking with GA was done by a definite and common procedure, while GPTMS crosslinking potency was investigated after 5, 10, 24, and 48 h synthesis periods and the fabrication method was adjusted in order for preparation of GMs with optimized morphological and compositional characteristics. The prepared GMs were then evaluated and compared as drug delivery systems for the antibiotic vancomycin (Vm). Morphological observations, FTIR, ninhydrin assay, swelling behavior evaluation and Hydrolytic degradation analysis proved successful modification of GMs and revealed that increasing synthesis time from 5 h to 24 h and 48 h, when using GPTMS as crosslinker, led to formation of morphologically-optimized GMs with highest crosslinking degree (∼50%) and the slowest hydrolytic degradation rate. Such GMs also exhibited most sustained release period of Vm. The antibacterial test results against gram-positive bacterium Staphylococcus aureus, were in accordance with the release profiles of Vm, as well. Together, GPTMS-crosslinked GMs with their preferable characteristics and known as biocompatible gelatin-siloxane hybrids, could act as proper drug delivery systems for the sustained release of the antibiotic vancomycin.

Novel antibacterial biodegradable Fe-Mn-Ag alloys produced by mechanical alloying.

Various compositions and synthesis methods of biodegradable iron-based alloys have been studied aiming for the use of temporary medical implants. However, none is focused on nano-structured alloy and on adding antibacterial property to the alloy. In this study, new Fe-30Mn-(1-3)Ag alloys were synthesized by means of mechanical alloying and assessed for their microstructure, mechanical properties, corrosion rate, antibacterial activity and cytotoxicity. Results showed that the alloy with 3 wt% Ag content displayed the highest relative density, shear strength, micro hardness and corrosion rate. However, optimum cytotoxicity and the antibacterial activity were reached by the alloy with 1 wt% Ag content. The compositional and processing effects of the alloys' properties are further discussed in this work.

Inhibitor of PI3K/Akt Signaling Pathway Small Molecule Promotes Motor Neuron Differentiation of Human Endometrial Stem Cells Cultured on Electrospun Biocomposite Polycaprolactone/Collagen Scaffolds.

Small molecules as useful chemical tools can affect cell differentiation and even change cell fate. It is demonstrated that LY294002, a small molecule inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway, can inhibit proliferation and promote neuronal differentiation of mesenchymal stem cells (MSCs). The purpose of this study was to investigate the differentiation effect of Ly294002 small molecule on the human endometrial stem cells (hEnSCs) into motor neuron-like cells on polycaprolactone (PCL)/collagen scaffolds. hEnSCs were cultured in a neurogenic inductive medium containing 1 µM LY294002 on the surface of PCL/collagen electrospun fibrous scaffolds. Cell attachment and viability of cells on scaffolds were characterized by scanning electron microscope (SEM) and 3-(4,5-dimethylthiazoyl-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. The expression of neuron-specific markers was assayed by real-time PCR and immunocytochemistry analysis after 15 days post induction. Results showed that attachment and differentiation of hEnSCs into motor neuron-like cells on the scaffolds with Ly294002 small molecule were higher than that of the cells on tissue culture plates as control group. In conclusion, PCL/collagen electrospun scaffolds with Ly294002 have potential for being used in neural tissue engineering because of its bioactive and three-dimensional structure which enhances viability and differentiation of hEnSCs into neurons through inhibition of the PI3K/Akt pathway. Thus, manipulation of this pathway by small molecules can enhance neural differentiation.

Purmorphamine as a Shh Signaling Activator Small Molecule Promotes Motor Neuron Differentiation of Mesenchymal Stem Cells Cultured on Nanofibrous PCL Scaffold.

There is variety of stem cell sources but problems in ethical issues, contamination, and normal karyotype cause many limitations in obtaining and using these cells. The cells in Wharton's jelly region of umbilical cord are abundant and available stem cells with low immunological incompatibility, which could be considered for cell replacement therapy. Small molecules have been presented as less expensive biologically active compounds that can regulate different developmental process. Purmorphamine (PMA) is a small molecule that, according to some studies, possesses certain differentiation effects. In this study, we investigated the effect of the PMA on Wharton's jelly mesenchymal stem cell (WJ-MSC) differentiation into motor neuronal lineages instead of sonic hedgehog (Shh) on PCL scaffold. After exposing to induction media for 15 days, the cells were characterized for expression of motor neuron markers including PAX6, NF-H, Islet1, HB9, and choline acetyl transferase (ChAT) by quantitative reverse transcription (PCR) and immunocytochemistry. Our results demonstrated that induced WJ-MSCs with PMA could significantly express motor neuron markers in RNA and protein levels 15 days post induction. These results suggested that WJ-MSCs can differentiate to motor neuron-like cells with PMA on PCL scaffold and might provide a potential source in cell therapy for nervous system.