Evaluation of Inhibitory Effects of Caffeine on Human Carcinoma Cells.

One of the world's most consumed medications is caffeine which is available in the vast majority of beverages. Previously, some effects of caffeine have been evaluated including its inhibitory effect on cancer cells. But, the influence of caffeine on esophagus carcinoma squamous cells (CSC) and head and neck carcinoma cells still has not well understood. Herein, the relation between different amounts of caffeine with the proliferation rate of human esophagus carcinoma squamous cell line KYSE-30 as well as human head and neck carcinoma cell line HN5 was evaluated. Furthermore, concentrations of caffeine were adjusted and their effect on cells were studied. The inhibitory effects of caffeine on cells were measured using the conventional colorimetric MTT assay after 3 and 7 day of incubation. Our findings are suggested that caffeine has a significant inhibitory effect on both cell lines at the concentrations of 20, 50, and 70 milli-mol (mmol). The result shows that caffeine can prevent the proliferation of carcinoma cells and it is a perfect candidate for therapeutic applications.

PCL/gelatin nanofibrous scaffolds with human endometrial stem cells/Schwann cells facilitate axon regeneration in spinal cord injury.

The significant consequences of spinal cord injury (SCI) include sensory and motor disability resulting from the death of neuronal cells and axon degeneration. In this respect, overcoming the consequences of SCI including the recovery of sensory and motor functions is considered to be a difficult tasks that requires attention to multiple aspects of treatment. The breakthrough in tissue engineering through the integration of biomaterial scaffolds and stem cells has brought a new hope for the treatment of SCI. In the present study, human endometrial stem cells (hEnSCs) were cultured with human Schwann cells (hSC) in transwells, their differentiation into nerve-like cells was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunocytochemistry techniques. The differentiated cells (co-hEnSC) were then seeded on the poly ε-caprolactone (PCL)/gelatin scaffolds. The SEM images displayed the favorable seeding and survival of the cells on the scaffolds. The seeded scaffolds were then transplanted into hemisected SCI rats. The growth of neuronal cells was confirmed with immunohistochemical study using NF-H as a neuronal marker. Finally, the Basso, Beattie, and Bresnahan (BBB) test confirmed the recovery of sensory and motor functions. The results suggested that combination therapy using the differentiated hEnSC seeded on PCL/gelatin scaffolds has the potential to heal the injured spinal cord and to limit the secondary damage.

Reduction of marginal mass required for successful islet transplantation in a diabetic rat model using adipose tissue-derived mesenchymal stromal cells.

BACKGROUND AIMS: Adipose tissue-derived mesenchymal stromal cells (AT-MSCs), widely known as multipotent progenitors, release several cytokines that support cell survival and repair. There are in vitro and in vivo studies reporting the regenerative role of AT-MSCs possibly mediated by their protective effects on functional islet cells as well as their capacity to differentiate into insulin-producing cells (IPCs). METHODS: On such a basis, our goal in the present study was to use three different models including direct and indirect co-cultures and islet-derived conditioned medium (CM) to differentiate AT-MSCs into IPCs and to illuminate the molecular mechanisms of the beneficial impact of AT-MSCs on pancreatic islet functionality. Furthermore, we combined in vitro co-culture of islets and AT-MSCs with in vivo assessment of islet graft function to assess whether co-transplantation of islets with AT-MSCs can reduce marginal mass required for successful islet transplantation and prolong graft function in a diabetic rat model. RESULTS: Our findings demonstrated that AT-MSCs are suitable for creating a microenvironment favorable for the repair and longevity of the pancreas ß cells through the improvement of islet survival and maintenance of cell morphology and insulin secretion due to their potent properties in differentiation. Most importantly, hybrid transplantation of islets with AT-MSCs significantly promoted survival, engraftment and insulin-producing function of the graft and reduced the islet mass required for reversal of diabetes. CONCLUSIONS: This strategy might be of therapeutic potential solving the problem of donor islet material loss that currently limits the application of allogeneic islet transplantation as a more widespread therapy for type 1 diabetes.

A new approach for pancreatic tissue engineering: human endometrial stem cells encapsulated in fibrin gel can differentiate to pancreatic islet beta-cell.

Metabolic diabetes mellitus as the most serious and prevalent metabolic disease in the world has various complications. The most effective treatment of type I diabetes seems to be islet cell transplantation. Shortage of donors and difficult procedures and high rate of rejection have always restricted this approach. Tissue engineering is a novel effective solution to many medical problems such as diabetes. Endometrial mesenchymal stem cells as a lineage which have the potential to differentiate to mesodermal and endodermal tissues seem to be suitable for this purpose. Fibrin hydrogel with a high degree of biocompatibility and specific properties making it similar to normal pancreas seems to be an ideal scaffold. After successfully isolating stem cells (hEnSCs) from human endometrium, a three-step protocol was used to differentiate them into pancreatic beta cells. Fibrin was used as 3D scaffold. After 2 weeks, cells formed clusters like islets cells, and secretion of insulin was measured by chemiluminescence. PDX1, proinsulin, and c-peptide as special markers of ß cells were detected by immunofluorescence. Expression of glucagon, PDX1, and insulin genes in mRNA level was detected by Real time PCR and gel electrophoresis. The former showed higher levels of gene expression in 3D cultures. SEM analysis showed good integrity between cells and scaffold. No toxicity was detected with fibrin scaffold by MTT assay.

Preparation and characterization of 3D bioprinted gelatin methacrylate hydrogel incorporated with curcumin loaded chitosan nanoparticles for in vivo wound healing application.

This study developed a biomimetic composite bioink consisting of gelatin methacrylate (GelMA) /chitosan nanoparticles (CSNPs) for extrusion-based 3D bioprinting. Additionally, curcumin(Cur)-loaded nanoparticles were incorporated which increased the proliferation and antibacterial activity of biomimetic skin constructs. The hydrogel, curcumin-loaded NPs, and the biocomposite was characterized chemically and physically. The results indicated proper modified gelatin with tunable physical characteristics, e.g., swelling ratio and biodegradability up to 1200 % and 25 days, respectively. In addition, the characterized CSNPs showed good distribution with a size of 370 nm and a zeta potential of 41.1 mV. We investigated the mechanical and cytocompatibility properties of chitosan nanoparticles encapsulated in hydrogel for emulating an extracellular matrix suitable for skin tissue engineering. CSNPs entrapped in GelMA (15 % w/v) exhibited controlled drug release during 5 days, which was fitted into various kinetic models to study the mass transfer mechanism behavior. Also, the composite hydrogels were effective as a barrier against both gram-positive and gram-negative bacteria at a concentration of 50 µg/ml nanoparticles in GelMA 15 %. Furthermore, the biocomposite was applied on Wistar rats for wound healing. As a result, this study provides a GelMA-NP50-Cur3 scaffold that promotes cell proliferation and decreases microbial infections in wounds.

Exploring the various effects of Cu doping in hydroxyapatite nanoparticle.

Adding foreign ions to hydroxyapatite (HAp) is a popular approach for improving its properties. This study focuses on the effects of calcium substitution with copper in HAp. Instead of calcium, copper ions were doped into the structure of hydroxyapatite nanoparticles at 1%, 3%, and 5% concentrations. XRD analysis showed that the amount of substituted copper was less than needed to generate a distinct phase, yet its lattice parameters and crystallinity slightly decreased. Further, the results of degradation tests revealed that copper doping in hydroxyapatite doubled calcium ion release in water. The incorporation of copper into the apatite structure also boosted the HAp zeta potential and FBS protein adsorption onto powders. According to antibacterial investigations, a concentration of 200 mg/ml of hydroxyapatite containing 5% copper was sufficient to effectively eradicate E. coli and S. aureus bacteria. Furthermore, copper improved hydroxyapatite biocompatibility. Alkaline phosphatase activity and alizarin red tests showed that copper in hydroxyapatite did not inhibit stem cell differentiation into osteoblasts. Also, the scratch test demonstrated that copper-containing hydroxyapatite extract increased HUVEC cell migration. Overall, our findings demonstrated the utility of incorporating copper into the structure of hydroxyapatite from several perspectives, including the induction of antibacterial characteristics, biocompatibility, and angiogenesis.

3D-bioprinted GelMA/gelatin/amniotic membrane extract (AME) scaffold loaded with keratinocytes, fibroblasts, and endothelial cells for skin tissue engineering.

Gelatin-methacryloyl (GelMA) is a highly adaptable biomaterial extensively utilized in skin regeneration applications. However, it is frequently imperative to enhance its physical and biological qualities by including supplementary substances in its composition. The purpose of this study was to fabricate and characterize a bi-layered GelMA-gelatin scaffold using 3D bioprinting. The upper section of the scaffold was encompassed with keratinocytes to simulate the epidermis, while the lower section included fibroblasts and HUVEC cells to mimic the dermis. A further step involved the addition of amniotic membrane extract (AME) to the scaffold in order to promote angiogenesis. The incorporation of gelatin into GelMA was found to enhance its stability and mechanical qualities. While the Alamar blue test demonstrated that a high concentration of GelMA (20%) resulted in a decrease in cell viability, the live/dead cell staining revealed that incorporation of AME increased the quantity of viable HUVECs. Further, gelatin upregulated the expression of KRT10 in keratinocytes and VIM in fibroblasts. Additionally, the histological staining results demonstrated the formation of well-defined skin layers and the creation of extracellular matrix (ECM) in GelMA/gelatin hydrogels during a 14-day culture period. Our study showed that a 3D-bioprinted composite scaffold comprising GelMA, gelatin, and AME can be used to regenerate skin tissues.

Cartilage tissue engineering using decellularized biomatrix hydrogel containing TGF-ß-loaded alginate microspheres in mechanically loaded bioreactor.

Physiochemical tissue inducers and mechanical stimulation are both efficient variables in cartilage tissue fabrication and regeneration. In the presence of biomolecules, decellularized extracellular matrix (ECM) may trigger and enhance stem cell proliferation and differentiation. Here, we investigated the controlled release of transforming growth factor beta (TGF-ß1) as an active mediator of mesenchymal stromal cells (MSCs) in a biocompatible scaffold and mechanical stimulation for cartilage tissue engineering. ECM-derived hydrogel with TGF-ß1-loaded alginate-based microspheres (MSs) was created to promote human MSC chondrogenic development. Ex vivo explants and a complicated multiaxial loading bioreactor replicated the physiological conditions. Hydrogels with/without MSs and TGF-ß1 were highly cytocompatible. MSCs in ECM-derived hydrogel containing TGF-ß1/MSs showed comparable chondrogenic gene expression levels as those hydrogels with TGF-ß1 added in culture media or those without TGF-ß1. However, constructs with TGF-ß1 directly added within the hydrogel had inferior properties under unloaded conditions. The ECM-derived hydrogel group including TGF-ß1/MSs under loading circumstances formed better cartilage matrix in an ex vivo osteochondral defect than control settings. This study demonstrates that controlled local delivery of TGF-ß1 using MSs and mechanical loading is essential for neocartilage formation by MSCs and that further optimization is needed to prevent MSC differentiation towards hypertrophy.

3D printing of complicated GelMA-coated Alginate/Tri-calcium silicate scaffold for accelerated bone regeneration.

Polymer-based composite scaffolds are an attractive class of biomaterials due to their suitable physical and mechanical performance as well as appropriate biological properties. When such composites contain osteoinductive ceramic nanopowders, it is possible, in principle, to stimulate the seeded cells to differentiate into osteoblasts. However, reproducibly fabricating and developing an appropriate niche for cells' activities in three-dimensional (3D) scaffolds remains a challenge using conventional fabrication techniques. Additive manufacturing provides a new strategy for the fabrication of complex 3D structures. Here, an extrusion-based 3D printing method was used to fabricate the Alginate (Alg)/Tri-calcium silicate (C3S) bone scaffolds. To improve physical and biological attributes, scaffolds were coated with gelatin methacryloyl (GelMA), a biocompatible viscose hydrogel. Conducting a combination of experimental techniques and molecular dynamics simulations, it is found that the composition ratio of Alg/C3S governs intermolecular interactions among the polymer and ceramic, affecting the product performance. Investigating the effects of various C3S amounts in the bioinks, the 90/10 composition ratio of Alg/C3S is known as the optimum content in developed bioinks. Accordingly, the printability of high-viscosity inks is boosted by improved hierarchical interactions among assemblies, which in turn leads to better nanoscale alignment in extruded macroscopic filaments. Conducting multiple tests on specimens, the GelMA-coated Alg/C3S scaffolds (with a composition ratio of 90/10) were shown to have improved mechanical qualities and cell adhesion, spreading, proliferation, and osteogenic differentiation, compared to the bare scaffolds, making them better candidates for further future research. Overall, the in-silico and in vitro studies of GelMA-coated 3D-printed Alg/C3S scaffolds open new aspects for biomaterials aimed at the regeneration of large- and complicated-bone defects through modifying the extrusion-based 3D-printed constructs.

Tissue-Engineered Core-Shell Silk-Fibroin/Poly-l-Lactic Acid Nerve Guidance Conduit Containing Encapsulated Exosomes of Human Endometrial Stem Cells Promotes Peripheral Nerve Regeneration.

Nerve guide conduits (NGCs) have been shown to be less efficient than nerve autografts in peripheral nerve regeneration. To address this issue, we developed for the first time a novel tissue-engineered nerve guide conduit structure encapsulated with human endometrial stem cell (EnSC) derived exosomes, which promoted nerve regeneration in rat sciatic nerve defects. In this study, we initially indicated the long-term efficacy and safety impacts of newly designed double layered SF/PLLA nerve guide conduits. Then the regeneration effects of SF/PLLA nerve guide conduits containing exosomes derived from human EnSCs were evaluated in rat sciatic nerve defects. The human EnSC derived exosomes were isolated from the supernatant of human EnSC cultures and characterized. Subsequently, the human EnSC derived exosomes were encapsulated in constructed NGCs by fibrin gel. For in vivo studies, entire 10 mm peripheral nerve defects were generated in rat sciatic nerves and restored with NGC encapsulated with human EnSC derived exosomes (Exo-NGC group), nerve guide conduits, and autografts. The efficiency of the NGCs encapsulated with human EnSCs derived exosomes in assisting peripheral nerve regeneration was investigated and compared with other groups. The in vivo results demonstrated that encapsulated human EnSC derived exosomes in NGC (Exo-NGC) significantly benefitted nerve regeneration based on motor function, sensory reaction, and electrophysiological results. Furthermore, immunohistochemistry with histopathology results showed the formation of regenerated nerve fibers, along with blood vessels that newly were developed, as a result of the exosome functions in the Exo-NGC group. These outcomes illustrated that the newly designed core-shell SF/PLLA nerve guide conduit encapsulated with human EnSC derived exosomes enhanced the regeneration process of axons and improved the functional recovery of rat sciatic nerve defects. So, encapsulated human EnSC-derived exosomes in a core-shell SF/PLLA nerve guide conduit are a potential therapeutic cell-free treatment for peripheral nerve defects.

Differentiation of human endometrial stem cells encapsulated in alginate hydrogel into oocyte-like cells.

Introduction: Human endometrial mesenchymal stem cells (hEnMSCs) are a rich source of mesenchymal stem cells (MSCs) with multi-lineage differentiation potential, making them an intriguing tool in regenerative medicine, particularly for the treatment of reproductive and infertility issues. The specific process of germline cell-derived stem cell differentiation remains unknown, the aim is to study novel ways to achieve an effective differentiation method that produces adequate and functioning human gamete cells. Methods: We adjusted the optimum retinoic acid (RA) concentration for enhancement of germ cell-derived hEnSCs generation in 2D cell culture after 7 days in this study. Subsequently, we developed a suitable oocyte-like cell induction media including RA and bone morphogenetic protein 4 (BMP4), and studied their effects on oocyte-like cell differentiation in 2D and 3D cell culture media utilizing cells encapsulated in alginate hydrogel. Results: Our results from microscopy analysis, real-time PCR, and immunofluorescence tests revealed that 10 µM RA concentration was the optimal dose for inducing germ-like cells after 7 days. We examined the alginate hydrogel structural characteristics and integrity by rheology analysis and SEM microscope. We also demonstrated encapsulated cell viability and adhesion in the manufactured hydrogel. We propose that in 3D cell cultures in alginate hydrogel, an induction medium containing 10 µM RA and 50 ng/mL BMP4 can enhance hEnSC differentiation into oocyte-like cells. Conclusion: The production of oocyte-like cells using 3D alginate hydrogel may be viable in vitro approach for replacing gonad tissues and cells.

Portable hand-held bioprinters promote in situ tissue regeneration.

Three-dimensional bioprinting, as a novel technique of fabricating engineered tissues, is positively correlated with the ultimate goal of regenerative medicine, which is the restoration, reconstruction, and repair of lost and/or damaged tissue function. The progressive trend of this technology resulted in developing the portable hand-held bioprinters, which could be used quite easily by surgeons and physicians. With the advent of portable hand-held bioprinters, the obstacles and challenges of utilizing statistical bioprinters could be resolved. This review attempts to discuss the advantages and challenges of portable hand-held bioprinters via in situ tissue regeneration. All the tissues that have been investigated by this approach were reviewed, including skin, cartilage, bone, dental, and skeletal muscle regeneration, while the tissues that could be regenerated via this approach are targeted in the authors' perspective. The design and applications of hand-held bioprinters were discussed widely, and the marketed printers were introduced. It has been prospected that these facilities could ameliorate translating the regenerative medicine science from the bench to the bedside actively.

Synergy effects of copper and L-arginine on osteogenic, angiogenic, and antibacterial activities.

Copper (Cu) ions have been found to exert antibacterial and angiogenic effects. However, some studies have indicated that it inhibits osteogenesis at high concentrations. On the other hand, L-arginine (Arg) is a semi-essential amino acid required for various biological processes, including osteogenic and angiogenic activities. As a result, we hypothesized that combining Arg with Cu ions would reduce its inhibitory effects on osteogenesis while increasing its angiogenic and antibacterial capabilities. To assess osteogenic and angiogenic activities, we employed rat bone marrow mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs), respectively. The gram-positive bacteria Staphylococcus epidermidis (S. epidermidis), Staphylococcus aureus (S. aureus), and the gram-negative bacterium Escherichia coli (E. coli) were used to investigate bacterial behaviors. According to ALP activity and calcium deposition outcomes, copper ions inhibited osteogenic development of MSCs at 100 µM; however, Arg supplementation somewhat mitigated the inhibitory effects. Furthermore, Copper and Arg synergistically stimulated migration and tube formation of HUVECs. According to our findings, copper ions and Arg in the range of 1-100 µM had no antibacterial effect on any examined bacteria. However, at a dose of 20 mM, copper demonstrated antibacterial activity, which was boosted by Arg. Overall, these findings suggest that a combination of copper and Arg may be more beneficial for bone regeneration than either copper or Arg alone.

Hyaluronic acid/gelatin microcapsule functionalized with carbon nanotube through laccase-catalyzed crosslinking for fabrication of cardiac microtissue.

Carbon nanotube (CNT) and gelatin (Gela) molecules are effective substrates in promoting engineered cardiac tissue functions. This study developed a microfluidic-based encapsulation process for biomimetic hydrogel microcapsule fabrication. The hydrogel microcapsule was produced through a coaxial double orifice microfluidic technique and a water-in-oil emulsion system in two sequential processes. The phenol (Ph) substituted Gela (Gela-Ph) and CNT (CNT-Ph), respectively as cell-adhesive and electrically conductive substrates were incorporated in hyaluronic acid (HA)-based hydrogel through laccase-mediated crosslinking. The Cardiomyocyte-enclosing microcapsule fabricated and cellular survival, function, and possible difference in the biological activity of encapsulated cells within micro vehicles were investigated. The coaxial microfluidic method and Lac-mediated crosslinking reaction resulted in spherical vehicle production in 183 µm diameter at 500 capsules/min speed. The encapsulation process did not affect cellular viability and harvested cells from microcapsule proliferated well likewise subcultured cells in tissue culture plate. The biophysical properties of the designed hydrogel, including mechanical strength, swelling, biodegradability and electroconductivity upregulated significantly for hydrogels decorated covalently with Gela-Ph and CNT-Ph. The tendency of the microcapsule for the spheroid formation of cardiomyocytes inside the proposed microcapsule occurred 3 days after encapsulation. Interestingly, immobilized Gela-Ph and CNT-Ph promote cellular growth and specific cardiac markers. Overall, the microfluidic-based encapsulation technology and synthesized biomimetic substrates with electroconductive properties demonstrate desirable cellular adhesion, proliferation, and cardiac functions for engineering cardiac tissue.

Commercialization and regulation of regenerative medicine products: Promises, advances and challenges.

The ultimate goal of regenerative medicine is to repair, regenerate, or reconstruct functional loss in failed tissues and/or organs. Although regenerative medicine is a relatively new field, multiple diverse research groups are helping regenerative medicine reach its objectives. All endeavors in this field go through in silico, in vitro, in vivo, and clinical trials which are prerequisites to translating such approaches from the bench to the bedside. However, despite such promise, there are only a few regenerative medicine approaches that have actually entered commercialization due to extensive demands for the inclusion of multiple rules, principles, and finances, to reach the market. This review covers the commercialization of regenerative medicine, including its progress (or lack thereof), processes, regulatory concerns, and immunological considerations to name just a few key areas. Also, commercially available engineered tissues, including allografts, synthetic substitutes, and 3D bioprinting inks, along with commercially available cell and gene therapeutic products, are reviewed. Clinical applications and future perspectives are stated with a clear road map for improving the regenerative medicine field.

A network analysis of angiogenesis/osteogenesis-related growth factors in bone tissue engineering based on in-vitro and in-vivo data: A systems biology approach.

The principal purpose of tissue engineering is to stimulate the injured or unhealthy tissues to revive their primary function through the simultaneous use of chemical agents, cells, and biocompatible materials. Still, choosing the appropriate protein as a growth factor (GF) for tissue engineering is vital to fabricate artificial tissues and accelerate the regeneration procedure. In this study, the angiogenesis and osteogenesis-related proteins' interactions are studied using their related network. Three major biological processes, including osteogenesis, angiogenesis, and angiogenesis regulation, were investigated by creating a protein-protein interaction (PPI) network (45 nodes and 237 edges) of bone regeneration efficient proteins. Furthermore, a gene ontology and a centrality analysis were performed to identify essential proteins within a network. The higher degree in this network leads to higher interactions between proteins and causes a considerable effect. The most highly connected proteins in the PPI network are the most remarkable for their employment. The results of this study showed that three significant proteins including prostaglandin endoperoxide synthase 2 (PTGS2), TEK receptor tyrosine kinase (TEK), and fibroblast growth factor 18 (FGF18) were involved simultaneously in osteogenesis, angiogenesis, and their positive regulatory. Regarding the available literature, the results of this study confirmed that PTGS2 and FGF18 could be used as a GF in bone tissue engineering (BTE) applications to promote angiogenesis and osteogenesis. Nevertheless, TEK was not used in BTE applications until now and should be considered in future works to be examined in-vitro and in-vivo.

Comparison of insulin secretion by transduced adipose-derived and endometrial-derived stem cells in 2D and 3D cultures on fibrin scaffold.

Type 1 diabetes is a metabolic disorder caused by the loss or dysfunction of ß-cells in the pancreas. Organ shortage is a critical concern of diabetic patients in need of beta islet transplantation. Tissue engineered islets are promising alternatives to traditional organ transplantation. Recent progress in stem cell biology and gene cloning techniques has raised hopes for the generation of insulin producing cells (IPCs) without the need of immunosuppression. The purpose of this study was to produce IPCs using human adipose-derived stem cells (hADSCs) and human endometrial-derived stem cells (hEnSCs) and also to compare the level of insulin secretion by these cells in 2D and 3D culture systems on fibrin scaffolding. Stem cells differentiation was carried out through transduction with an insulin over expression lentiviral vector. Real-time PCR and immunocytochemistry confirmed the successful transduction of both cell types. Both cell types showed comparable insulin secretion by ELISA.3D culture resulted in higher amounts of insulin secretion of the two cell types versus 2D as control. This study showed that insulin gene delivery to the stem cells could be an efficient method for producing IPCs and fibrin encapsulation enhances the functionality of these cells.

Cell attachment effects of collagen nanoparticles on crosslinked electrospun nanofibers.

Since collagen is naturally a main extracellular matrix protein, it has been applied widely in skin's tissue engineering scaffolds to mimics the characteristics of extracellular matrix for proper transplantation of living cells. However, there are challenges that come with application of this natural polymer such as high solubility in aqueous environments which requires further consideration such as chemically cross-linking in order to stabilization. But these treatments also affect its functionality and finally cellular behaviors on scaffold. In this research we evaluated the suitability of collagen nanofibers versus collagen nanoparticles for cell adhesion and viability on glutaraldehyde cross-linked scaffolds. Appling a dual-pump electrospining machine a blend PCL-Gelatin from one side and collagen nanofibers or collagen nanoparticles from the other side were collected on the collector. The fabricated scaffolds were characterized by scanning electron microscopy, contact angle, and mechanical analysis. The cell viability, adhesion and morphology were studied respectively using MTT assay, hoechst staining and scanning electron microscopy. The results indicated significantly improvement of cell viability, adhesion and better spreading on scaffolds with collagen nanoparticles than collagen nanofibers. It seems changes in surface morphology, viscoelastic moduli and swelling ability following cross-linking with glutaraldehyde in scaffold with collagen nanoparticles are still favorable for cellular proliferation. Based on these results, in the case of glutaraldehyde cross-linking, application of collagen nanoparticles rather than collagen nanofibers in tissue regeneration scaffolds will better mimic the extracellular matrix characteristics; and preserve the viability and adhesion of seeded cells.

Therapeutic effects of combination of platelet lysate and sulfasalazine administration in TNBS-induced colitis in rat.

Inflammatory bowel disease (IBD) is a chronic and idiopathic disease with gastrointestinal dysfunction. Current therapeutic approaches in IBD have several limitations such as, harmful side effects and high price for biologic drugs. It sounds that finding of an effective, safe and inexpensive strategy to overcome IBD is critical. Platelet derivatives, as biological pool of wide range of growth factors and cytokines, are widely used in regenerative medicine for treatment of soft and hard tissue lesions. We sought to determine whether platelet lysate (PL) alone or in combination with sulfasalazine (reference drug) can be a valuable strategy for overcoming IBD. In the present study, we investigated and compared the daily and alternate-day administration of PL alone or combined with sulfasalazine for treating colitis in a rat model of IBD. Histological damage scores of TNBS-induced colitis were reduced by co-administration of every alternate day PL and sulfasalazine. Pro-inflammatory cytokines TNF-α, IL-1 and IL-6 were decreased and anti-inflammatory cytokines IL-10 and TGF-ß were increased after treatment with PL compared to that in the TNBS group. Furthermore, combined treatment with PL and sulfasalazine decreased apoptosis and inhibited the NF-κB signaling pathway. In conclusion, the combined administration of PL with conventional IBD therapy is able to effectively ameliorate IBD through modulation of inflammatory status.

The Role of Stem Cells in the Treatment of Cerebral Palsy: a Review.

Cerebral palsy (CP) is a neuromuscular disease due to injury in the infant's brain. The CP disorder causes many neurologic dysfunctions in the patient. Various treatment methods have been used for the management of CP disorder. However, there has been no absolute cure for this condition. Furthermore, some of the procedures which are currently used for relief of symptoms in CP cause discomfort or side effects in the patient. Recently, stem cell therapy has attracted a huge interest as a new therapeutic method for treatment of CP. Several investigations in animal and human with CP have demonstrated positive potential of stem cell transplantation for the treatment of CP disorder. The ultimate goal of this therapeutic method is to harness the regenerative capacity of the stem cells causing a formation of new tissues to replace the damaged tissue. During the recent years, there have been many investigations on stem cell therapy. However, there are still many unclear issues regarding this method and high effort is needed to create a technology as a perfect treatment. This review will discuss the scientific background of stem cell therapy for cerebral palsy including evidences from current clinical trials.