Role of bone 1stem cell-seeded 3D polylactic acid/polycaprolactone/hydroxyapatite scaffold on a critical-sized radial bone defect in rat.

Osteoconductive biomaterials were used to find the most reliable materials in bone healing. Our focus was on the bone healing capacity of the stem cell-loaded and unloaded PLA/PCL/HA scaffolds. The 3D scaffold of PLA/PCL/HA was characterized by scanning electron microscopy (SEM), rheology, X-ray diffraction (XRD), and Fourier transform-infrared (FT-IR) spectroscopy. Bone marrow stem cells (BMSCs) have multipotential differentiation into osteoblasts. Forty Wistar male rats were used to organize four experimental groups: control, autograft, scaffold, and BMSCs-loaded scaffold groups. qRT-PCR showed that the BMSCs-loaded scaffold had a higher expression level of CD31 and osteogenic markers compared with the control group (P < 0.05). Radiology and computed tomography (CT) scan evaluations showed significant improvement in the BMSCs-loaded scaffold compared with the control group (P < 0.001). Biomechanical estimation demonstrated significantly higher stress (P < 0.01), stiffness (P < 0.001), and ultimate load (P < 0.01) in the autograft and BMSCs-loaded scaffold groups compared with the untreated group and higher strain was seen in the control group than the other groups (P < 0.01). Histomorphometric and immunohistochemical (IHC) investigations showed significantly improved regeneration scores in the autograft and BMSCs-loaded scaffold groups compared with the control group (P < 0.05). Also, there was a significant difference between the scaffold and control groups in all tests (P < 0.05). The results depicted that our novel approach will allow to develop PLA/PCL/HA 3D scaffold in bone healing via BMSC loading.

Substrate stiffness affects the morphology and gene expression of epidermal neural crest stem cells in a short term culture.

According to the intrinsic plasticity of stem cells, controlling their fate is a critical issue in cell-based therapies. Recently, a growing body of evidence has suggested that substrate stiffness can affect the fate decisions of various stem cells. Epidermal neural crest stem cells as one of the main neural crest cell derivatives hold great promise for cell therapies due to presenting a high level of plasticity. This study was conducted to define the influence of substrate stiffness on the lineage commitment of these cells. Here, four different polyacrylamide hydrogels with elastic modulus in the range of 0.7-30 kPa were synthesized and coated with collagen and stem cells were seeded on them for 24 hr. The obtained data showed that cells can attach faster to hydrogels compared with culture plate and cells on <1 kPa stiffness show more neuronal-like morphology as they presented several branches and extended longer neurites over time. Moreover, the transcription of actin downregulated on all hydrogels, while the expression of Nestin, Tubulin, and PDGFR-α increased on all of them and SOX-10 and doublecortin gene expression were higher only on <1 kPa. Also, it was revealed that soft hydrogels can enhance the expression of glial cell line-derived neurotrophic factor, neurotrophin-3, and vascular endothelial growth factor in these stem cells. On the basis of the results, these cells can respond to the substrate stiffness in the short term culture and soft hydrogels can alter their morphology and gene expression. These findings suggested that employing proper substrate stiffness might result in cells with more natural profiles similar to the nervous system and superior usefulness in therapeutic applications.

Effectiveness of a biodegradable 3D polylactic acid/poly(ɛ-caprolactone)/hydroxyapatite scaffold loaded by differentiated osteogenic cells in a critical-sized radius bone defect in rat.

The effects of a scaffold made of polylactic acid, poly (ɛ-caprolactone) and hydroxyapatite by indirect 3D printing method with and without differentiated bone cells was tested on the regeneration of a critical radial bone defect in rat. The scaffold characterization and mechanical performance were determined by the rheology, scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and Fourier transform infrared spectrometry. The defects were created in forty Wistar rats which were randomly divided into the untreated, autograft, scaffold cell-free, and differentiated bone cell-seeded scaffold groups (n = 10 in each group). The expression level of angiogenic and osteogenic markers, analyzed by quantitative real time-polymerase chain reaction (in vitro), significantly improved (p < 0.05) in the scaffold group compared to the untreated one. Radiology and computed tomography scan demonstrated a significant improvement in the cell-seeded scaffold group compared to the untreated one (p < 0.001). Biomechanical, histopathological, histomorphometric, and immunohistochemical investigations showed significantly better regeneration scores in the cell-seeded scaffold and autograft groups compared to the untreated group (p < 0.05). The cell-seeded scaffold and autograft groups did show comparable results on the 80th day post-treatment (p > 0.05), however, most results in the scaffold group were significantly higher than the untreated group (p < 0.05). Differentiated bone cells can enhance bone regeneration potential of the scaffold.

Bioactive antibacterial bilayer PCL/gelatin nanofibrous scaffold promotes full-thickness wound healing.

Treatment of diabetic, chronic, and full-thickness wounds is a challenge as these injuries usually lead to infections that cause delayed and inappropriate healing. Therefore, fabrication of skin scaffolds with prolonged antibacterial properties are of great interest. Due to this demand, bilayered nanofibrous scaffolds were fabricated based on polycaprolactone and gelatin. The top layer of these scaffolds contained amoxicillin as a model drug and the bottom layer was loaded with zinc oxide nanoparticles to accelerate wound healing. Several characterization techniques including FTIR, SEM, swelling, tensile test, in vitro degradation, drug release, antibacterial activity, and MTT assay were used to assess physical, mechanical, and biological properties of produced nanofibers. SEM results demonstrated that bilayered scaffolds have smooth bead-free microstructures while in vitro release test showed that samples have a sustained release for amoxicillin up to 144 h (tested time). Disk diffusion assessment confirmed the potency of scaffolds for hindering bacterial growth while results of cytotoxicity evaluation revealed that scaffolds could effectively accelerate cell proliferation. Finally, in vivo tests on full-thickness rat models revealed that fabricated nanofibers accelerate wound contraction, increase collagen deposition and angiogenesis, and prevent scar formation. Altogether, results showed that fabricated scaffolds are promising candidates for treatment of full-thickness wounds.

Preparation and characterization of PLA/PCL/HA composite scaffolds using indirect 3D printing for bone tissue engineering.

3D printing-based technologies can fabricate scaffolds offer great precision to control internal architecture and print complicated structures based upon the defect site. However, the materials used in the direct printing are restricted depending on the printing technology used and the indirect one can overcome this limitation. In the present study, indirect 3D printing approach was used to develop bone scaffolds from polylactic acid/ polycaprolactone/ hydroxyapatite (PLA/PCL/HA) composites. Casting of the composite suspensions was done into a dissolvable 3D printed negative mold, in order to achieve simultaneous macro- and micro-porous composites, using freeze drying/particle leaching method. To evaluate morphology, functional groups, and elemental analysis of the scaffolds, scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and energy dispersive spectroscopy (EDS) were respectively used. Scaffolds' porosity was measured with the aid of liquid replacement technique. Also, the mechanical strength of scaffolds was examined by compression test and measuring the compressive modulus Considering the microstructure, porosity and pore size as well as mechanical property, the scaffold composed of PLA/PCL 70/30 w/w and 35% HA was more favorable. The PLA/PCL/HA 70/30-35% scaffold presented a porosity of 77%, an average pore size of 160 µm, and Young's modulus of 1.35 MPa. Cell adhesion, viability and mineral deposits formation for PLA/PCL/HA scaffolds at PLA/PCL ratios of 70/30, 50/50 and 30/70 and the fixed amount of HA (35%) were also studied in vitro by the means of MG63 cells. The cytotoxicity assessment showed that the cells could be viable and proliferate on the scaffolds. The results indicated that composite scaffold with the PLA/PCL weight ratio of70/30 accomplished more favorable properties in terms of biocompatibility, viability, and osteoinduction property.

Cardiovascular stents: overview, evolution, and next generation.

Compared to bare-metal stents (BMSs), drug-eluting stents (DESs) have been regarded as a revolutionary change in coronary artery diseases (CADs). Releasing pharmaceutical agents from the stent surface was a promising progress in the realm of cardiovascular stents. Despite supreme advantages over BMSs, in-stent restenosis (ISR) and long-term safety of DESs are still deemed ongoing concerns over clinically application of DESs. The failure of DESs for long-term clinical use is associated with following factors including permanent polymeric coating materials, metallic stent platforms, non-optimal drug releasing condition, and factors that have recently been supposed as contributory factors such as degradation products of polymers, metal ions due to erosion and degradation of metals and their alloys utilizing in some stents as metal frameworks. Discovering the direct relation between stent materials and associating adverse effects is a complicated process, and yet it has not been resolved. For clinical success it is of significant importance to optimize DES design and explore novel strategies to overcome all problems including inflammatory response, delay endothelialization, and sub-acute stent thrombosis (ST) simultaneously. In this work, scientific reports are reviewed particularly focusing on recent advancements in DES design which covers both potential improvements of existing and recently novel prototype stent fabrications. Covering a wide range of information from the BMSs to recent advancement, this study mostly sheds light on DES's concepts, namely stent composition, drug release mechanism, and coating techniques. This review further reports different forms of DES including fully biodegradable DESs, shape-memory ones, and polymer-free DESs.

Effect of organic/inorganic nanoparticles on performance of polyurethane nanocomposites for potential wound dressing applications.

This study focuses on the evaluation and modification of polyurethane (PU) membranes containing organic and inorganic nanoparticles for potential use as a wound dressing. For the purpose of PU nanocomposite preparation, chitosan (CS) was converted into nanoparticles by the ionic-gelation method to improve its blending capability with the PU matrix. These CS nanoparticles (nano-CS) were obtained as a hydrophilic organic filler with different contents and were utilized along with inorganic titanium dioxide (TiO2) nanoparticles in the nanocomposite membrane preparation. The membranes were prepared using phase inversion technique and their microstructure was controlled by manipulating the solvent non-solvent exchange rate. Obtained results demonstrate that addition of polymer solvent to nonsolvent induced a microstructure alteration from finger-like to sponge-like, which is more suitable for fluid uptake and consequently more useful for wound dressing applications. Similar results were obtained by introduction of nanoparticles to membranes. Due to the polar nature of nanoparticles and their effects on PU structure, prepared membranes showed 71.5% improve in swelling when compared to neat PU. Moreover, the reinforcement effect of nanoparticles caused an 18.94% increase in ultimate tensile strength in comparison with bare PU film, while elongation at break was not affected considerably. In addition, prepared PU nanocomposite films showed suitable antibacterial activity of 69% against Staphylococcus aureus and did not show any toxicity to human fibroblast cells. Based on these results, simultaneous use of TiO2 and chitosan nanoparticles can improve both physical and antibacterial properties of PU as an ideal wound dressing.

Correction to: Solidification of hydatid cyst fluid with an injectable chitosan/carboxymethylcellulose/ß-glycerophosphate hydrogel for effective control of spillage during aspiration of hydatid cysts.

The original version of this article unfortunately contained a mistake: the spelling of the Shadi Hassanajili's name was incorrect. The corrected name is given above.

Solidification of hydatid cyst fluid with an injectable chitosan/carboxymethylcellulose/ß-glycerophosphate hydrogel for effective control of spillage during aspiration of hydatid cysts.

Cystic echinococcosis (CE)/hydatid cyst is one of the most important helminthic diseases in the world. The treatment of hydatid cyst ranges from surgical intervention to chemotherapy, although the efficacy of chemotherapy is still unclear. Postoperative complication which results from the spillage of cysts during surgical operation is one of the most important concerns in surgical treatment of hydatid cyst. The aim of the current study was to solidify the hydatid cyst fluid (HCF) with an injectable and thermosensitive chitosan (CS)/carboxymethyl cellulose (CMC)/ß-glycerol phosphate (BGP) hydrogel for effective control of spillage during the aspiration of hydatid cysts. Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), water uptake, rheological analysis, and Alamar Blue cytotoxicity assay were employed to characterize the hydrogel. A five level with three times replication at the central point using a central composite design (CCD), which is a response surface methodology (RSM), was used to optimize the experimental conditions. Assessment of the produced hydrogel showed that the intermolecular interactions of amino groups of chitosan and hydrogen groups of CMC were correctively established and appreciable swelling with a good strength was obtained. Hydrogels morphology had a porous structure. Rheological analysis showed that CS/CMC/BGP blends had a phase transition (32-35 °C) of sol-gel close to the body temperature. Alamar Blue cytotoxicity assay showed that CS (1.75%)/CMC (1.4%)/BGP (2.9%) had IC50 values of 0.598, 0.235 and 0.138 (µg/µL) for 24, 48 and 72 h, which indicated that the produced polymer solution had no significant cytotoxic effect for human fibroblast cell line. In vitro injection of the polymer solution of CS/CMC/BGP with CS/CMC ratio of 1.75/1.4 was done on HCF (1 mL polymer solution to 3 mL of HCF) at 37 °C with a final concentration of 2.9% for BGP resulting in solidification of HCF in less than 45 min.