Optimization of the Modular Reinforced Bone Scaffold for Customized Alveolar Bone Defects.

A modular reinforced bone scaffold with enhanced mechanical properties has recently been developed by our group. It includes: 1) A load-bearing module: a skeleton which is made of a slowly degradable material, undertaking mechanical necessities of the scaffold, and 2) A bioreactive module: a porous and biodegradable component undertaking biological necessities of the scaffold. The load-bearing module is placed into the bio-reactive module to reinforce it. This paper is dedicated to optimizing the load-bearing module for a certain customized alveolar bone defect. More specifically, a 3D-printed skeleton, made of polycaprolactone (PCL), is optimized based on the boundary conditions of the defect shape using the finite element method (FEM) to minimize the weight (to minimize the amount of PCL) and maximize the mechanical properties and porosity of the skeleton. Gelatin foam has been incorporated into the optimized skeleton through the aminolysis process to form the bio-reactive module. The mechanical characterization confirmed that the optimized load-bearing module has a bridge-like shape and can significantly improve the mechanical properties of the scaffold. Also, in vitro studies showed that the Revised manuscript (clean version) Click here to view linked References fabricated scaffold can improve cell proliferation and osteogenesis. This kind of scaffold can be useful for the treatment of critical-sized defects.

Microfluidic-assisted fabrication of reverse micelle/PLGA hybrid microspheres for sustained vascular endothelial growth factor delivery.

In this study, poly (d, l-lactide-co-glycolide) (PLGA) composite microspheres containing anhydrous reverse micelle (R.M.) dipalmitoylphosphatidylcholine (DPPC) nanoparticles loaded vascular endothelial growth factor (VEGF) were produced using microfluidic platforms. The VEGF-loaded R.M. nanoparticles (VRM) were achieved by initial self-assembly and subsequent lipid inversion of the DPPC vesicles. The fabricated VRMs were encapsulated into the PLGA matrix by flow-focusing geometry microfluidic platforms. The encapsulation efficiency, in vitro release profile, and the bioactivity of the produced composite microspheres were investigated. The release study showed that VEGF was slowly released from the PLGA composite microspheres over 28 days with a reduced initial burst (18 â€¯± â€¯4.17% in the first 24 H). The VEGF stability during encapsulation and release period was also investigated, and the results indicated that encapsulated VEGF was well preserved. Also, the bioactivity assay of the PLGA composite microspheres on human umbilical vein endothelial cells was confirmed that the encapsulated VEGF was utterly active. The present monodisperse and controllable VEGF-loaded microspheres with reproducible manner could be widely used in tissue engineering and therapeutic applications.

Polyvinyl alcohol modified polyvinylidene fluoride-graphene oxide scaffold promotes osteogenic differentiation potential of human induced pluripotent stem cells.

Tissue engineering is fast becoming a key approach in bone medicine studies. Designing the ideally desirable combination of stem cells and scaffolds are at the hurt of efforts for producing implantable bone substitutes. Clinical application of stem cells could be associated with serious limitations, and engineering scaffolds that are able to imitate the important features of extracellular matrix is a major area of challenges within the field. In this study, electrospun scaffolds of polyvinylidene fluoride (PVDF), PVDF-graphene oxide (GO), PVDF-polyvinyl alcohol (PVA) and PVDF-PVA-GO were fabricated to study the osteogenic differentiation potential of human induced pluripotent stem cells (iPSCs) while cultured on fabricated scaffolds. Scanning electron microscopy study, viability assay, relative gene expression analysis, immunocytochemistry, alkaline phosphates activity, and calcium content assays confirmed that the osteogenesis rate of hiPSCs cultured on PVDF-PVA-Go is significantly higher than other scaffolds. Here, we showed that the biocompatible, nontoxic, flexible, piezoelectric, highly porous and interconnected three-dimensional structure of electrospun PVDF-PVA-Go scaffold in combination with hiPSCs (as the stem cells with significant advantageous in comparison to other types) makes them a highly promising scaffold-stem cell system for bone remodeling medicine. There was no evidence for the superiority of PVDF-GO or PVDF-PVA scaffold for osteogenesis, compared to each other; however both of them showed better potentials as to PVDF scaffold.

Bone tissue engineering gelatin-hydroxyapatite/graphene oxide scaffolds with the ability to release vitamin D: fabrication, characterization, and in vitro study.

Developing smart scaffolds with drug release capability is one of the main approaches to bone tissue engineering. The current study involves the fabrication of novel gelatin (G)-hydroxyapatite (HA)-/vitamin D (VD)-loaded graphene oxide (GO) scaffolds with different concentrations through solvent-casting method. Characterizations confirmed the successful synthesis of HA and GO, and VD was loaded in GO with 36.87 ± 4.87% encapsulation efficiency. Physicochemical characterizations showed that the scaffold containing 1% VD-loaded GO had the best mechanical properties and its porosity percentage and density was in the range of natural spongy bone. All scaffolds were degraded after 1-month, subjecting to phosphate buffer saline. The release profile of VD did not match any mathematical kinetics model, porosities and the degradation rate of the scaffolds were dominant controlling factors of release behavior. Studies on the bioactivity of scaffolds immersed in simulated body fluid indicated that VD and HA could encourage the formation of secondary apatite crystals in vitro. Buccal fat pad-derived stem cells (BFPSCs) were seeded on the scaffolds, MTT assay, alkaline phosphatase activity as an indicator of osteoconductivity, and cell adhesion were conducted in order to evaluate in vitro biological responses. All scaffolds highly supported cell adhesion, MTT assay indicated better cell viability in 0.5% VD-loaded GO containing scaffold, and the scaffold enriched with 2% VD-loaded GO performed the most ALP activity. The results demonstrated the potential of these scaffolds to induce bone regeneration. Developing smart scaffolds with drug release capability is one of the main approaches to bone tissue engineering. The current study involves the fabrication of novel gelatin (G)-hydroxyapatite (HA)-/vitamin D (VD)-loaded graphene oxide (GO) scaffolds with different concentrations through solvent-casting method. Characterizations confirmed the successful synthesis of HA and GO, and VD was loaded in GO with 36.87 ± 4.87% encapsulation efficiency. Physicochemical characterizations showed that the scaffold containing 1% VD-loaded GO had the best mechanical properties and its porosity percentage and density was in the range of natural spongy bone. All scaffolds were degraded after 1-month, subjecting to phosphate buffer saline. The release profile of VD did not match any mathematical kinetics model, porosities and the degradation rate of the scaffolds were dominant controlling factors of release behavior. Studies on the bioactivity of scaffolds immersed in simulated body fluid indicated that VD and HA could encourage the formation of secondary apatite crystals in vitro. Buccal fat pad-derived stem cells (BFPSCs) were seeded on the scaffolds, MTT assay, alkaline phosphatase activity as an indicator of osteoconductivity, and cell adhesion were conducted in order to evaluate in vitro biological responses. All scaffolds highly supported cell adhesion, MTT assay indicated better cell viability in 0.5% VD-loaded GO containing scaffold, and the scaffold enriched with 2% VD-loaded GO performed the most ALP activity. The results demonstrated the potential of these scaffolds to induce bone regeneration.

Novel microfluidic graphene oxide-protein amperometric biosensor for detecting sulfur compounds.

Sulfur compounds are essential for many industries and organisms; however, they cause serious respiratory problems in human beings. Therefore, determination of sulfur concentration is of paramount importance. The research approach in the field of detecting contaminants has led to smaller systems that provide faster and more effective ways for diagnosis purposes. In this study, a novel portable amperometric graphene oxide-protein biosensor platform is investigated. The main characteristic of this structure is the implementation of a microfluidic configuration. With albumin metalloprotein as the biorecognition element, graphene oxide was synthesized and characterized by transmission electron microscopy and Fourier-transform infrared spectroscopy (FTIR). Albumin protein was stabilized on the surface of graphene oxide by the application of the N-(3-dimethylamionpropyl)-N-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide method. The stabilization was confirmed by FTIR and electrochemistry analyses. The calibration curve of sulfur concentration was determined. When the graphene oxide-protein complex was stabilized by nephion on the surface of the microfluidic system, the response time reduced to 50 Sec, which is a relatively faster response among the similar studies and validated the significant effect of the microfluidic system. The nanosystem had an optimized pH of 7.4 and exhibited high sensitivity in determining sulfide. The results confirm that the portable graphene oxide-protein nanosystem has a fast and accurate response in detecting sulfide.

Graphene oxide-l-arginine nanogel: A pH-sensitive fluorouracil nanocarrier.

Nowadays, putting forward an accurate cancer therapy method with minimal side effects is an important topic of research. Nanostructures, for their ability in controlled and targeted drug release on specific cells, are critical materials in this field. In this study, a pH-sensitive graphene oxide-l-arginine nanogel was synthesized to carry and release 5-fluorouracil. Optimized conditions using statistical analysis, based on the maximum relative viscosity of nanogel, were evaluated: 5.489 for the concentration of l-arginine and 2.404 for pH. The prepared nanogels were characterized using scanning electron microscope and transmission electron microscope images and Fourier-transform infrared spectroscopic analysis. Cytotoxicity was assessed using the sulforhodamine B (SRB) assay on MCF-7 breast cancer cells. The fluorouracil release was measured by the dialysis bag method, UV spectrophotometry, and fluorouracil calibration diagram. Results proved the successful controlled release of fluorouracil at pH 5.4 and the beneficial role of graphene-oxide- l-arginine- fluorouracil nanogel in eliminating cancer cells.

A glassy carbon electrode modified with reduced graphene oxide and gold nanoparticles for electrochemical aptasensing of lipopolysaccharides from Escherichia coli bacteria.

An electrochemical aptasensor is described for the voltammetric determination of lipopolysaccharide (LPS) from Escherichia coli 055:B5. Aptamer chains were immobilized on the surface of a glassy carbon electrode (GCE) via reduced graphene oxide and gold nanoparticles (RGO/AuNPs). Fast Fourier transform infrared, X-ray diffraction and transmission electron microscopy were used to characterize the nanomaterials. Cyclic voltammetry, square wave voltammetry and electrochemical impedance spectroscopy were used to characterize the modified GCE. The results show that the modified electrode has a good selectivity for LPS over other biomolecules. The hexacyanoferrate redox system, typically operated at around 0.3 V (vs. Ag/AgCl) is used as an electrochemical probe. The detection limit is 30 fg·mL-1. To decrease the electrochemical potential for detection of LPS, Mg/carbon quantum dots were used as redox active media. They decrease the detection potentialto 0 V and the detection of limit (LOD) to 1 fg·mL-1. The electrode was successfully used to analyze serum of patients and healthy persons. Graphical abstractSchematic representation of the modification of reduced graphene oxide gold nanoparticles with aptamer chains to immobilize on the glassy carbon electrode surface for electrochemical detection of lipopolysaccharides.

Antagonistic effect of co-exposure to short-multiwalled carbon nanotubes and benzo[a]pyrene in human lung cells (A549).

In theenvironment, co-exposure to short-multiwalled carbon nanotubes (S-MWCNTs) and polycyclic aromatic compounds (PAHs) has been reported. In the co-exposure condition, the adsorption of PAHs onto MWCNTs may reduce PAHs toxic effect. The objective of this study was to investigate the cytotoxicity of S-MWCNTs and benzo[a]pyrene (B[a]P) individually, and in combination in human lung cell lines (A549). The adsorption of B[a]P onto MWCNTs was measured spectrometrically. In vitro toxicity was assessed through cell viability, reactive oxygen species (ROS) generation, apoptosis, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) generation experiments. The S-MWCNTs demonstrated cytotoxicity through the generation of ROS, apoptosis, and 8-OHdG in A549 cells. Co-exposure to S-MWCNTs and B[a]P demonstrated a significant reduction in ROS generation and apoptosis compared with the sum of their separate toxic effects at the same concentrations. Decreasing the bioavailability of B[a]P by MWCNT interaction is the probable reason for the antagonistic effects of the co-exposure condition. The findings of this study will contribute to a better understanding of the health effects of co-exposures to air pollutants and could be a starting point for modifying future health risk assessments.

Optimizing the nanostructure of graphene oxide/silver/arginine for effective wound healing.

In this study, we introduce a novel graphene oxide/silver/arginine (GO/Ag/Arg) nanohybrid structure, which can act as an angiogenesis promoter and provide antibacterial nanostructure for improving the wound healing process. GO/Ag nanostructure has been optimized in terms of the GO/Ag mass ratio and pH values using central composite design and the response surface method to increase the Ag loading efficiency. Then, Arg was chemically introduced to the surface of GO/Ag nanostructure. Electrospun polycaprolactone (PCL)-GO/Ag/Arg nanocomposite was successfully fabricated and characterized. The synthesized nanocomposite demonstrated not only a great antibacterial effect on both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacterial species, but appropriate biocompatibility against L929 fibroblastic cell lines. The results demonstrated that the preparation of the PCL-GO/Ag/Arg nanocomposite at a concentration of 1.0 wt% GO/Ag/Arg possessed the best biological and mechanical features. In vivo experiments also revealed that the use of optimized PCL-GO/Ag/Arg nanocomposite, after 12 d of treatment, led to significant increase in the healing process and also regeneration of the wound via reconstruction of a thickened epidermis layer on the wound surface, which was confirmed by histological analysis. In conclusion, the proposed approach can introduce a novel notion for preparing antibacterial material that significantly promotes angiogenesis.

Normalization of doxorubicin release from graphene oxide: New approach for optimization of effective parameters on drug loading.

Graphene oxide (GO) has been recently introduced as a suitable anticancer drug carrier, which could be loaded with doxorubicin (DOX) as a general chemotherapy agent. Herein, the attempts were made to optimize the effective parameters on both loading and release of DOX on GO. GO and GO-DOX were characterized using transition electron microscopy , zeta potential, Raman spectroscopy, UV-visible spectroscopy, and Fourier transform infrared spectroscopy. In addition, loading and releasing behaviors of DOX on GO were studied in terms of different temperature and pH values. The primary optimized values of pH and temperature for best-loaded amount of DOX were 8.9 and 309 K, respectively. Moreover, we found that the smallest amount of released DOX, in pH of cancer microenvironment (5.4), occurs when DOX had been previously loaded in pH 7.8 and 310 K. Although the highest amount of loaded DOX was in basic pH, the results of efficient release of DOX from the GO-DOX complex and also cellular toxicity assay revealed that the best pH for loading of DOX on GO was 7.8. Therefore, in addition to optimization of parameters for efficient loading of DOX on GO, this study suggested that normalization of a released drug compared with the amount of a loaded drug could be a new approach for optimization of drug loading on nanocarriers.

Electrochemical nanobiosensor based on reduced graphene oxide and gold nanoparticles for ultrasensitive detection of microRNA-128.

Acute lymphoblastic leukemia (ALL) is one of the most prevalent cancers in children and microRNA-128 is amongst the most useful biomarkers not only for diagnosis of ALL, but also for discriminating ALL from acute myeloid leukemia (AML). In this study, a novel electrochemical nanobiosensor based on reduced graphene oxide (RGO) and gold nanoparticles (AuNPs) has been fabricated to detect miRNA-128. Cyclic Voltametery (CV), Square Wave Voltametery (SWV) and Electrochemical Impedance Spectroscopy (EIS) have been applied to characterize the nanobiosensor. Hexacyanoferrate as a label-free and methylene blue as a labeling material were used in the design of the nanobiosensors. It was found that the modified electrode has excellent selectivity and sensitivity to miR-128, with a limit of detection of 0.08761 fM in label-free and 0.00956 fM in labeling assay. Additionally, the examination of real serum samples of ALL and AML patients and control cases confirms that the designed nanobiosensor has the potential to detect and discriminate these two cancers and the control samples.

Osteogenic Differentiation Potential of Adipose-Derived Mesenchymal Stem Cells Cultured on Magnesium Oxide/Polycaprolactone Nanofibrous Scaffolds for Improving Bone Tissue Reconstruction.

Purpose: Recently, bone tissue engineering as a new strategy is used to repair and replace bone defects due to limitations in allograft and autograft methods. In this regard, we prepared nanofibrous scaffolds composed of polycaprolactone (PCL) and magnesium oxide (MgO) nanoparticles using the electrospinning technique for possible bone tissue engineering applications. Methods: The fabricated composites were characterized via scanning electron microscopy (SEM) imaging of scaffolds and seeded cells, water contact angle, DAPI staining, and MTT assay. Then osteogenic differentiation of adipose-derived mesenchymal stem cells cultured on this composite scaffold was determined by standard osteogenic marker tests, including alkaline phosphatase (ALP) activity, calcium deposition, and expression of osteogenic differentiation genes in the laboratory conditions. Results: The SEM analysis demonstrated that the diameter of nanofibers significantly decreased from 1029.25±209.349 µm to 537.83+0.140 nm, with the increase of MgO concentration to 2% (P < 0.05). Initial adhesion and proliferation of the adipose-derived mesenchymal stem cells on MgO/PCL scaffolds were significantly enhanced with the increasing of MgO concentration (P < 0.05). The 2% MgO/PCL nanofibrous scaffold showed significant increase in ALP activity (P < 0.05) and osteogenic-related gene expressions (Col1a1 and OPN) (P < 0.05) in compared to pure PCL and (0, 0.5 and 1%) MgO/PCL scaffolds. Conclusion: According to the results, it was demonstrated that MgO/PCL composite nanofibers have considerable osteoinductive potential, and taking together adipose-derived mesenchymal stem cells-MgO/PCL composite nanofibers can be a proper bio-implant to usage for bone regenerative medicine applications. Future in vivo studies are needed to determine this composite therapeutic potential.

Culture and maintenance of neural progressive cells on cellulose acetate/graphene­gold nanocomposites.

In this study, the first CA nanofibers were fabricated by electrospinning under optimal conditions: flow rate of 0.5 ml/h, a voltage of 20 kV, electrospinning distance of 15 cm, and an internal temperature of 25 °C, and humidity of 38%. The used Graphene/gold nanoparticles for CA performance improvement were examined by TGA, XRD, and SEM analysis. Then the CA/graphene­gold nanocomposite was synthesized under optimum electrospinning conditions: flow rate 3 ml/h, voltage 20 kV, electrospinning distance 15 cm, internal temperature 26 °C, and humidity 36%. The SEM images revealed that the nanofibers' thicknesses of Graphene­gold NPs (CA1) and Chitosan (CA2) were 350 and 120 nm, respectively. The XRD diagrams of CA0, CA1 and CA2 revealed the peaks at 2θ, 8°, and 21° with Miller indices of (001) and (110) are related to CA (CA0), which proves its presence in other scaffolds. The FTIR analysis of samples indicated the presence of graphene­gold NPs in scaffolding CA1 and CA2. The CA2 nanofibers exhibited a high-water absorption capacity of about 2500% with the water contact-angle and Swelling method. The antibacterial properties of this nanocomposite were also confirmed by an antibacterial test on Staphylococcus aureus bacteria. The growth of Schwann cells on three scaffolds showed the highest growth of cells on CA1 scaffolds.

3D-printed bi-layered polymer/hydrogel construct for interfacial tissue regeneration in a canine model.

OBJECTIVES: There are complications in applying regenerative strategies at the interface of hard and soft tissues due to the limited designs of constructs that can accommodate different cell types in different sites. The problem originates from the challenges in the adhesion of dissimilar materials, such as polymers and hydrogels, that can be suitable for regenerating different tissues such as bone and soft tissues. This paper presents a design of a new hybrid construct in which a polymer (polycaprolactone (PCL)) membrane firmly adheres to a layer of hydrogen (gelatin). METHODS: PCL membranes with defined size and porosity were fabricated using 3D printing. The gelatin layer was attached to the PCL membranes using the aminolysis procedure. We have examined this construct for the application of Guided Bone Regeneration (GBR) as a typical surgical regenerative procedure of the oral cavity at the interface of bone and soft tissue. Complete in vitro and in vivo investigations on canine tibia bone defects have been performed. Histological analyses for fibrosis morphometric and bone morphometric evaluation, as well as bone-fibrosis histological grading and CBCT imaging, were conducted. RESULTS: Chemical and morphological studies of the membrane proved that gelatin was uniformly attached to the aminolyzed PCL membranes. The in vitro and in vivo studies indicated the membrane's biocompatibility, mechanical stability, and barrier function for the GBR application. Furthermore, in vitro study showed that the membranes could improve osteogenesis and the regeneration of bone defects. The results illustrated that the mean bone density in the membrane groups was about three times more than that of the control group. SIGNIFICANCE: The fabricated 3D-printed hybrid Gelatin/PCL bi-layered membrane can be a good candidate for interfacial tissue engineering and a promising membrane for GBR procedure.

A bioprinted composite hydrogel with controlled shear stress on cells.

In recent decades, three dimensional (3D) bio-printing technology has found widespread use in tissue engineering applications. The aim of this study is to scrutinize different parameters of the bioprinter - with the help of simulation software - to print a hydrogel so much so that avoid high amounts of shear stress which is detrimental for cell viability and cell proliferation. Rheology analysis was done on several hydrogels composed of different percentages of components: alginate, collagen, and gelatin. The results have led to the combination of percentages collagen:alginate:gelatin (1:4:8)% as the best condition which makes sol-gel transition at room temperature possible. The results have shown the highest diffusion rate and cell viability for the cross-linked sample with 1.5% CaCl2 for the duration of 1 h. Finally, we have succeeded in printing the hydrogel that is mechanically strong with suitable degradation rate and cell viability.

Impact of Lipid/Magnesium Hydroxide Hybrid Nanoparticles on the Stability of Vascular Endothelial Growth Factor-Loaded PLGA Microspheres.

The purpose of the present study is to characterize poly(d,l-lactide-co-glycolide) (PLGA) composite microcarriers for vascular endothelial growth factor (VEGF) delivery. To reduce the initial burst release and protect the bioactivity, VEGF is encapsulated in soybean l-α-phosphatidylethanolamine (PE) and l-α-phosphatidylcholine (PC) anhydrous reverse micelle (VEGF-RM) nanoparticles. Also, mesoporous nano-hexagonal Mg(OH)2 nanostructure (MNS)-loaded PE/PC anhydrous reverse micelle (MNS-RM) nanoparticles are synthesized to suppress the induced inflammation of PLGA acidic byproducts and regulate the release profile. The flow-focusing microfluidic geometry platforms are used to fabricate different combinations of PLGA composite microspheres (PLGA-CMPs) with MNSs, MNS-RM, VEGF-RM, and native VEGF. The essential parameters of each formulation, such as release profiles, encapsulation efficacy, bioactivity, inflammatory response, and cytotoxicity, are investigated by in vitro and in vivo studies. The results indicate that generated acidic byproducts during the hydrolytic degradation process of PLGA can be buffered, and pH values inside and outside microspheres can remain steady during degradation by MNSs. Furthermore, the significant improvement in the stability of the encapsulated VEGF is confirmed by the bioactivity assay. In vitro release study shows that the VEGF initial burst release is well minimized in the present microcarriers. The present monodisperse PLGA-CMPs can be widely used in various tissue engineering and therapeutic applications.

Ultra pH-sensitive detection of total and free prostate-specific antigen using electrochemical aptasensor based on reduced graphene oxide/gold nanoparticles emphasis on TiO2/carbon quantum dots as a redox probe.

The development of a rapid, sensitive, and straightforward detection method of prostate-specific antigen (PSA) is indispensable for the early diagnosis of prostate cancer (PCa). This work relates an electrochemical method using functionalized single-stranded DNA aptamer to diagnose PCa and benign prostate hyperplasia. The sensing platform relies on PSA recognition by aptamer/Au/GO-nanohybrid-modified glassy carbon electrode. Besides ferrocyanide TiO2/carbon quantum dots (CQDs) probe is used to investigate the effect of nanoparticle-containing electrolyte. Optimization of incubation time of aptamer/Au/GO-nanohybrid and volume fraction of nafion were done using Design Expert 10 software reporting 42.4 h and 0.095% V/V, respectively. In ferrocyanide medium, PSA detection as low as 3, 2.96, and 0.85 ng mL-1 was achieved with a dynamic range from 0.5 to 7 ng ml-1, in accord with clinical values, using cyclic voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy, respectively. Moreover, this sensor exhibited conspicuous performance in TiO2/CQDs-containing medium with different pH values of 5.4 and 8 to distinguish total PSA and free PSA, resulting in very low limit of detections, 0.028, and 0.007 ng ml-1, respectively. The results manifested the proposed system as a forthcoming sensor in a clinical and point of care analysis of PSA.

Synthesis of a novel nanocomposite containing chitosan as a three-dimensional printed wound dressing technique: Emphasis on gene expression.

In this study, a highly porous three-dimensional (3D)-printed wound healing core/shell scaffold fabricated using poly-lactic acid (PLA). The core of scaffold was composed of hyaluronic acid (HA), copper carbon dots (Cu-CDs), rosmarinic acid, and chitosan hydrogel. Cu-CDs were synthesized using ammonium hydrogen citrate under hydrothermal conditions. Formulation containing 1 mg ml-1 concentration of Cu-CDs showed an excellent antibacterial activity against gram bacteria. At 0.25 mg ml-1 of Cu-CDs concentration, scaffold had a good biocompatibility as confirmed by cytotoxicity assay on L929 fibroblast stem cells. in vivo wound healing experiments on groups of rats revealed that after 15 days of treatment, the optimal formulation of composite scaffold significantly improves the wound healing process compared to the PLA scaffold. This finding was confirmed by histological analysis and the relative expression of PDGF, TGF-ß, and MMP-1 genes. The biocompatible antibacterial CU-CDS/PLA/HA/chitosan/rosmarinic acid nanocomposite is a promising wound healing scaffold which highly accelerates the process of skin regeneration.

Theranostic applications of stimulus-responsive systems based on carbon dots.

Over recent years, many different nanoparticle-based drug delivery systems (NDDSs) have been developed. Recently the development of stimulus-responsive NDDSs has come into sharper focus. Carbon dots (CDs) possess outstanding features such as useful optical properties, good biocompatibility, and the ability for easy surface modification. Appropriate surface modification can allow these NDDSs to respond to various chemical or physical stimuli that are characteristic of their target cells or tissue (frequently malignant cells or tumors). The present review covers recent developments of CDs in NDDSs with a particular focus on internal stimulus response capability that allows simultaneous imaging and therapeutic delivery (theranostics). Relevant stimuli associated with tumor cells and tumors include pH levels, redox potential, and different enzymatic activities can be used to activate the CDs at the desired sites.

Fabrication, Rheological, and Compositional Characterization of Thermoresponsive Hydrogel from Cornea.

Fabricating thermoresponsive hydrogels from decellularized tissues is a trending and promising approach to develop novel biomaterials for tissue engineering and therapeutic purposes. There are differences in the characteristics of the produced hydrogels related to the source tissue as well as the decellularization and solubilization protocols used. Detailed characterization of the hydrogels will support the efforts to optimize their application as biomaterials for tissue engineering and therapeutics. Here, we describe an optimized method for fabricating an in situ thermoresponsive hydrogel from decellularized porcine cornea extracellular matrix (COMatrix), and provide a detailed characterization of its structure, thermoresponsive rheological behavior (heat-induced sol-gel transition), as well as exploring its protein composition using proteomics. COMatrix forms a transparent gel (10-min time to gelation) after in situ curing with heat, characterized by alteration in light absorbance and rheological indexes. The rheological characterization of heat-formed COMatrix gel shows similar behavior to common biomaterials utilized in tissue engineering. The fibrillar structure of COMatrix gel was observed by scanning electron microscopy showing that the density of fibers attenuates in lower concentrations. Mass spectrometry-based proteomic analysis revealed that COMatrix hydrogel is rich in proteins with known regenerative properties such as lumican, keratocan, and laminins in addition to structural collagen proteins (Data is available via ProteomeXchange with identifier PXD020606). COMatrix hydrogel is a naturally driven biomaterial with favorable biomechanical properties and protein content with potential application as a therapeutic biomaterial in ocular regeneration and tissue engineering. Impact statement Fabrication and application of decellularized porcine corneal extracellular matrix is an emerging approach for corneal tissue engineering and regeneration. There are several protocols for decellularization of porcine cornea with various efficiencies. Here, we are presenting an optimized protocol for decellularization of porcine cornea followed by fabrication of a thermoresponsive hydrogel from the decellularized cornea matrix. Moreover, the fabricated hydrogel was rheologically and compositionally characterized as crucial features to be employed for further application of this hydrogel in corneal tissue engineering and regeneration.