Harnessing IL-10 induced anti-inflammatory response in maturing macrophages in presence of electrospun dexamethasone-loaded PLLA scaffold.

The ultimate goal of tissue engineering is to repair and regenerate damaged tissue or organ. Achieving this goal requires blood vessel networks to supply oxygen and nutrients to new forming tissues. Macrophages are part of the immune system whose behavior plays a significant role in angiogenesis and blood vessel formation. On the other hand, macrophages are versatile cells that change their behavior in response to environmental stimuli. Given that implantation of a biomaterial is followed by inflammation; therefore, we reasoned that this inflammatory condition in tissue spaces modulates the final phenotype of macrophages. Also, we hypothesized that anti-inflammatory glucocorticoid dexamethasone improves modulating macrophages behavior. To check these concepts, we investigated the macrophages that had matured in an inflammatory media. Furthermore, we examined macrophages' behavior after maturation on a dexamethasone-containing scaffold and analyzed how the behavioral change of maturing macrophages stimulates other macrophages in the same environment. In this study, the expression of pro-inflammatory markers TNFa and NFκB1 along with pro-healing markers IL-10 and CD163 were investigated to study the behavior of macrophages. Our results showed that macrophages that were matured in the inflammatory media in vitro increase expression of IL-10, which in turn decreased the expression of pro-inflammatory markers TNFa and NFκB in maturing macrophages. Also, macrophages that were matured on dexamethasone-containing scaffolds decreased the expression of IL-10, TNFa, and NFκB and increase the expression of CD163 compared to the control group. Moreover, the modulation of anti-inflammatory response in maturing macrophages on dexamethasone-containing scaffold resulted in increased expression of TNFa and CD163 by other macrophages in the same media. The results obtained in this study, proposing strategies to improve healing through controlling the behavior of maturing macrophages and present a promising perspective for inflammation control using tissue engineering scaffolds.

Co-delivery of carboplatin and doxorubicin using ZIF-8 coated chitosan-poly(N-isopropyl acrylamide) nanoparticles through a dual pH/thermo responsive strategy to breast cancer cells.

A dual pH/temperature sensitive core-shell nanoformulation has been developed based on ZIF-8 coated with chitosan-poly(N-isopropyl acrylamide) (CS-PNIPAAm) for co-delivery of doxorubicin (DOX) and carboplatin (CBP) in breast cancer cells. The resulting nanoparticles (NPs) had particle sizes around 200 nm and a zeta potential of about +30 mV. The CBP and DOX loading contents in the final NPs were 11.6 % and 55.54 %, respectively. NPs showed a pH and thermoresponsive drug release profile with a sustained prolonged release under physiological conditions. The in vitro cytotoxicity experiments showed a significant synergism of CBP and DOX to induce the IC50 of 1.96 µg/mL in MCF-7 cells and 4.54 µg/mL in MDA-MB-231 cells. Also, the final NPs were safer than free DOX and CBP on normal cells. The in vitro study confirmed the higher potency of the designed NPs in combination therapy against breast cancer cells with lower side effects than free drugs.

Platelet rich fibrin and simvastatin-loaded pectin-based 3D printed-electrospun bilayer scaffold for skin tissue regeneration.

Designing multifunctional wound dressings is a prerequisite to prevent infection and stimulate healing. In this study, a bilayer scaffold (BS) with a top layer (TL) comprising 3D printed pectin/polyacrylic acid/platelet rich fibrin hydrogel (Pec/PAA/PRF) and a bottom nanofibrous layer (NL) containing Pec/PAA/simvastatin (SIM) was produced. The biodegradable and biocompatible polymers Pec and PAA were cross-linked to form hydrogels via Ca2+ activation through galacturonate linkage and chelation, respectively. PRF as an autologous growth factor (GF) source and SIM together augmented angiogenesis and neovascularization. Because of 3D printing, the BS possessed a uniform distribution of PRF in TL and an average fiber diameter of 96.71 ± 18.14 nm was obtained in NL. The Young's modulus of BS was recorded as 6.02 ± 0.31 MPa and its elongation at break was measured as 30.16 ± 2.70 %. The wound dressing gradually released growth factors over 7 days of investigation. Furthermore, the BS significantly outperformed other groups in increasing cell viability and in vivo wound closure rate (95.80 ± 3.47 % after 14 days). Wounds covered with BS healed faster with more collagen deposition and re-epithelialization. The results demonstrate that the BS can be a potential remedy for skin tissue regeneration.

Core-shell nanofibers containing L-arginine stimulates angiogenesis and full thickness dermal wound repair.

Despite the advances in medicine, wound healing is still challenging and piques the interest of biomedical engineers to design effective wound dressings using natural and artificial polymers. In present study, coaxial electrospinning was employed to fabricate core-shell nanofiber-based wound dressing, with core composed of polyacrylamide (PAAm) and shell comprising 0.5 % solution of L-Arginine (L-Arg) in aloe vera and keratin (AloKr). Aloe vera and keratin were added as natural polymers to promote angiogenesis, reduce inflammation, and provide antibacterial activity, whereas PAAm in core was used to improve the tensile properties of the wound dressing. Moreover, L-Arg was incorporated in shell to promote angiogenesis and collagen synthesis. The fiber diameter of PAAm/(AloKr/L-Arg) core-shell fibers was (93.33 ± 35.11 nm) with finer and straighter fibers and higher water holding capacity due to increased surface area to volume ratio. In terms of tensile properties, the PAAm/(AloKr/L-Arg) core-shell nanofibers with tensile strength and elastic modulus of 2.84 ± 0.27 MPa and 62.15 ± 5.32 MPa, respectively, showed the best mechanical performance compared to other nanofibers tested. Furthermore, PAAm/(AloKr/L-Arg) exhibited the highest L-Arg release (87.62 ± 3.02 %) and viability of L929 cells in vitro compared to other groups. In addition, the highest rate of in vivo full thickness wound healing was observed in PAAm/(AloKr/L-Arg) group compared to other groups. It significantly enhanced the angiogenesis, neovascularization, and cell proliferation. The prepared PAAm/(AloKr/L-Arg) core-shell nanofibrous dressing could be promising for full-thickness wound healing.

Clinical Outcomes and Effectiveness of CRLX101 for Solid Tumors: A Systematic Review and Meta-analysis.

BACKGROUND: While it has been demonstrated that delivery of cytotoxic chemotherapy using nanoparticles greatly improves patient drug tolerance and reduces toxicity when compared to the standard formulation, the crucial question of whether they also increase anticancer efficacy remains. The CRLX101 is a nanoparticle composed of cyclodextrin and 20(S)-camptothecin cytotoxic chemotherapy. OBJECTIVE: In order to compare the efficacy of the CRLX101 to its corresponding traditional formulation, we carried out this systematic literature search for randomized clinical and non-randomized trials. METHODS: Multiple electronic databases, including PubMed, Scopus, Embase, Web of Science, the Cochrane Library, and clinicaltrials.gov, were used to conduct a thorough literature search. By employing a technique akin to a random-effects model, the median of the study-specific was taken into account as the pooled median estimate with a 95% confidence interval. RESULTS: Finally, nine clinical studies were chosen for the meta-analysis. The treatment and control groups' overall survival were examined in five and three trials, respectively. Additionally, six out of nine trials and two out of nine trials, respectively, examined the treatment and control groups for progression-free survival (PFS). Meta-analysis revealed that the treatment group had a lower median overall survival (OS) but a greater median progression-free survival than the control group. CONCLUSION: Our meta-analysis shows that CRLX101 outperforms camptothecin in PFS despite its inferior OS. Unresolved pharmacology limits carrier-mediated drug therapeutic application. Carrier-mediated dosages may differ from normal formulations because they are rarely studied.

Graphene oxide-encapsulated baghdadite nanocomposite improved physical, mechanical, and biological properties of a vancomycin-loaded PMMA bone cement.

Polymethyl methacrylate (PMMA) bone cement is commonly used in orthopedic surgeries to fill the bone defects or fix the prostheses. These cements are usually containing amounts of a nonbioactive radiopacifying agent such as barium sulfate and zirconium dioxide, which does not have a good interface compatibility with PMMA, and the clumps formed from these materials can scratch metal counterfaces. In this work, graphene oxide encapsulated baghdadite (GOBgh) nanoparticles were applied as radiopacifying and bioactive agent in a PMMA bone cement containing 2 wt.% of vancomycin (VAN). The addition of 20 wt.% of GOBgh (GOBgh20) nanoparticles to PMMA powder caused a 33.6% increase in compressive strength and a 70.9% increase in elastic modulus compared to the Simplex® P bone cement, and also enhanced the setting properties, radiopacity, antibacterial activity, and the apatite formation in simulated body fluid. In vitro cell assessments confirmed the increase in adhesion and proliferation of MG-63 cells as well as the osteogenic differentiation of human adipose-derived mesenchymal stem cells on the surface of PMMA-GOBgh20 cement. The chorioallantoic membrane assay revealed the excellent angiogenesis activity of nanocomposite cement samples. In vivo experiments on a rat model also demonstrated the mineralization and bone integration of PMMA-GOBgh20 cement within four weeks. Based on the promising results obtained, PMMA-GOBgh20 bone cement is suggested as an optimal sample for use in orthopedic surgeries.

Design and preparation of an electromechanical implant prototype for an on-demand drug delivery.

INTRODUCTION: A bio-implant is a drug-delivery system that is implanted in the human body for a period of more than 30 days. Electromechanical systems are one type of bio-implant that has recently been introduced as a new generation of targeted drug delivery methods. The overarching goal of utilizing these systems is to integrate electrical and mechanical features in order to benefit from the numerous applications of these two systems when used together. The current study aimed to design a prototype of an electromechanical system using Fused Deposition Modeling (FDM), Selective Laser Sintering (SLS), and MultiJet Fusion (MJF) techniques for drug delivery that can release a specific drug dosage in the patient's body by connecting to a sensor or under the control of a signal sent by the physician. METHODS: Initially, the implant chambers were created in the form of a hollow cylinder, closed at one end, using three different types of 3D printers: FDM, SLS, and MJF. Each implant was then filled with a model drug (pentoxifylline) and sealed with a thin gold membrane. To achieve the lowest voltage required to melt the gold membrane, an electric circuit with controllable DC voltage generator was designed. Finally, the mechanical resistance, drug release rate, and surface morphology of the designed implants were evaluated. RESULTS: The MJF 3D printer, overally, had higher printing precision and repeatability than other printers; however, the implants printed by the FDM 3D printer were more accurate than other techniques (P value < 0.001), similar to the dimensions of the designed file. The mechanical resistance of the implants was also evaluated, and the polylactic acid implants printed by FDM had the highest value of Young's modulus in both the standard samples and the designed implants. During the 3-month drug leakage study, FDM 3D printed implant had a greater ability to store the desired drug load (P value < 0.001), Furthermore, the SEM micrographs revealed that the polylactic acid implants printed by FDM had minimal porosity in their structure and the layers were well adhered together. The gold membrane with a middle diameter of 2 mm required the lowest voltage of 6 V. As a result, the final electrical circuit was designed with smaller dimensions in order to achieve the voltage required to melt the gold membrane. CONCLUSION: Due to the lack of drug leakage and other mechanical studies, the electromechanical implant produced by the FDM 3D printer was chosen as the optimal electromechanical implant in this study. Along with the designed small circuit, this implant can release a drug dosage in the patient's body at the physician's demand.

Keratinocyte Exosomes for Topical Delivery of Tofacitinib in Treatment of Psoriasis: an In Vitro/ In Vivo Study in Animal Model of Psoriasis.

INTRODUCTION: Exosomes are extracellular vesicles in the range of 40-150 nm released from the cell membrane. Exosomes secreted by keratinocytes can communicate with other keratinocytes and immune cells with specific biomarkers at their surface, which may be effective on inflammation of psoriasis and its pathogenesis. OBJECTIVE: The present study aimed to formulate and study effectiveness of an exosomal delivery system of tofacitinib (TFC). METHODS: TFC was loaded by different methods in exosomes and then characterized for particle size, zeta potential, drug loading efficiency, and release efficiency. By comparing these parameters, the probe sonication method was chosen to load TFC into exosomes. The MTT assay was used to compare the cytotoxicity of the free drug with the TFC-loaded exosomes (TFC-Exo), and Real-time PCR was used to determine the expression levels of several genes involved in psoriasis expressed in the A-431 keratinocyte and their suppression after treatment. Animal model of psoriasis was induced in BALB/c mice by imiquimod and the efficacy of free TFC, and TFC-Exo were studies on macroscopic appearance and histopathological symptoms. RESULTS: Exosomes encapsulating TFC showed lower cytotoxicity in MTT assay, higher suppression the expression of TNF-a, IL-23, IL-6, and IL-15 genes in real-time PCR and better therapeutic effect on animal models compered to free TFC. CONCLUSIONS: This method of drug delivery for TFC may be effective on enhancing its therapeutic effects and reduction its side effects favorably in chronic administration.

Co-release of nitric oxide and L-arginine from poly (ß-amino ester)-based adhesive reprogram macrophages for accelerated wound healing and angiogenesis in vitro and in vivo.

Recently, insufficient angiogenesis and prolonged inflammation are crucial challenges of chronic skin wound healing. The sustained release of L-Arginine (L-Arg) and nitric oxide (NO) production can control immune responses, improve angiogenesis, enhance re-epithelialization, and accelerate wound healing. Here, we aim to improve wound healing via the controlled release of NO and L-Arg from poly (ß-amino ester) (PßAE). In this regard, PßAE is functionalized with methacrylate poly-L-Arg (PAMA), and the role of PAMA content (50, 66, and 75 wt%) on the adhesive properties, L-Arg, and NO release, as well as collagen deposition, inflammatory responses, and angiogenesis, is investigated in vitro and in vivo. Results show that the PAMA/ PßAE could provide suitable adhesive strength (~25 kPa) for wound healing application. In addition, increasing the PAMA content from 50 to 75 wt% results in an increased release of L-Arg (approximately 1.4-1.7 times) and enhanced NO production (approximately 2 times), promoting skin cell proliferation and migration. The in vitro studies also show that compared to PßAE hydrogel, incorporation of 66 wt% PAMA (PAMA 66 sample) reveals superior collagen I synthesis (~ 3-4 times) of fibroblasts, controlled pro-inflammatory and improved anti-inflammatory cytokines secretion of macrophages, and accelerated angiogenesis (~1.5-2 times). In vivo studies in a rat model with a full-thickness skin defect also demonstrate the PAMA66 sample could accelerate wound healing (~98 %) and angiogenesis, compared to control (untreated wound) and Tegaderm™ commercial wound dressing. In summary, the engineered multifunctional PAMA functionalized PßAE hydrogel with desired NO and L-Arg release, and adhesive properties can potentially reprogram macrophages and accelerate skin healing for chronic wound healing.

Efficacy of topical gabapentin in women with primary macular amyloidosis: A side-by-side triple-blinded randomized clinical trial.

BACKGROUND: Primary cutaneous macular amyloidosis (PCMA) is a chronic pruritic cutaneous disease characterized by heterogeneous extracellular deposition of amyloid protein in the skin. AIMS: This study aimed to evaluate the efficacy of topical 6% gabapentin cream for the treatment of patients with PCMA. MATERIALS AND METHODS: In this triple-blind clinical trial, a total of 34 patients, who were diagnosed with PCMA, treated using two different strategies of topical gabapentin as the active group and vehicle cream as the control group. RESULTS: Pruritus score reduction in both groups was statistically significant compared with the baseline value (p < 0.001). There was a significant pigmentation score reduction in intervention group compared with control group after 1 month of the study (p < 0.001). The differences of pigmentation score changes between the groups were not significant at month 2 (p = 0.52) and month 3 (p = 0.22). CONCLUSIONS: The results of this study suggest that topical gabapentin cream may be effective as a topical agent in the treatment of pruritus associated with PCMA without any significant adverse effects. It is recommended to perform similar studies with a larger sample size and longer duration in both sexes.

A double-layer cellulose/pectin-soy protein isolate-pomegranate peel extract micro/nanofiber dressing for acceleration of wound healing.

Multi-layered wound dressings can closely mimic the hierarchical structure of the skin. Herein, a double-layer dressing material is fabricated through electrospinning, comprised of a nanofibrous structure as a healing-support layer or the bottom layer (BL) containing pectin (Pec), soy protein isolate (SPI), pomegranate peel extract (P), and a cellulose (Cel) microfiber layer as a protective/monitoring layer or top layer (TL). The formation of a fine bilayer structure was confirmed using scanning electron microscopy. Cel/Pec-SPI-P dressing showed a 60.05 % weight loss during 7 days of immersion in phosphate buffered solution. The ultimate tensile strength, elastic modulus, and elongation at break for different dressings were within the range of 3.14-3.57 MPa, 32.26-36.58 MPa, and 59.04-63.19 %, respectively. The release of SPI and phenolic compounds from dressings were measured and their antibacterial activity was evaluated. The fabricated dressing was non-cytotoxic following exposure to human keratinocyte cells. The Cel/Pec-SPI-P dressing exhibited excellent cell adhesion and migration as well as angiogenesis. More importantly, in vivo experiments on Cel/Pec-SPI-P dressings showed faster epidermal layer formation, blood vessel generation, collagen deposition, and a faster wound healing rate. Overall, it is anticipated that the Cel/Pec-SPI-P bilayer dressing facilitates wound treatment and can be a promising approach for clinical use.

3D printed polylactic acid-based nanocomposite scaffold stuffed with microporous simvastatin-loaded polyelectrolyte for craniofacial reconstruction.

Critical sized craniofacial defects are among the most challenging bone defects to repair, due to the anatomical complexity and aesthetic importance. In this study, a polylactic acid/hardystonite-graphene oxide (PLA/HTGO) scaffold was fabricated through 3D printing. In order to upgrade the 3D printed scaffold to a highly porous scaffold, its channels were filled with pectin-quaternized chitosan (Pec-QCs) polyelectrolyte solution containing 0 or 20 mg/mL of simvastatin (Sim) and then freeze-dried. These scaffolds were named FD and FD-Sim, respectively. Also, similar PLA/HTGO scaffolds were prepared and dip coated with Pec-QCs solution containing 0 or 20 mg/mL of Sim and were named DC and DC-Sim, respectively. The formation of macro/microporous structure was confirmed by morphological investigations. The release of Sim from DC-Sim and FD-Sim scaffolds after 28 days was measured as 77.40 ± 5.25 and 86.02 ± 3.63 %, respectively. Cytocompatibility assessments showed that MG-63 cells had the highest proliferation, attachment and spread on the Sim containing scaffolds, especially FD-Sim. In vivo studies on a rat calvarial defect model revealed that an almost complete recovery occurred in the group treated with FD-Sim scaffold after 8 weeks and the defect was filled with newly formed bone. The results of this study acknowledge that the FD-Sim scaffold can be a perfect candidate for calvarial defect repair.

Targeted delivery of liposomal Ribociclib to SLC7A5 transporters in breast cancer cells.

This study aimed to prepare SLC7A5 transporters targeted liposomes of Ribociclib (RB) by stear(o)yl conjugation of Phe, Asp, Glu amino acids to liposomes as targeting moieties. The liposomes were optimized for their formulations. Cell analysis on two cell lines of MCF-7 and NIH-3T3 were done including; cell viability test by MTT assay, cellular uptake, and cell cycle arrest by flow cytometry. The optimal liposomes showed the particle size of 123.6 ± 1.3 nm, drug loading efficiency and release efficiency of 83.87% ± 1.33% and 60.55% ± 0.46%, respectively. The RB loaded liposomes showed no hemolysis activity. Targeted liposomes increased cytotoxicity on MCF-7 cells more significantly than NIH-3T3 cells. Cell flow cytometry indicated that targeted liposomes uptake was superior to plain (non-targted) liposomes and free drug. Free drug and RB-loaded liposomes interrupted cell cycle in G1. However, amino acid-targeted liposomes arrested cells more than the free drug at this stage. Targeted liposomes reduced cell cycle with more interruption in the G2/M phase compared to the negative control.

Keratin- and VEGF-Incorporated Honey-Based Sponge-Nanofiber Dressing: An Ideal Construct for Wound Healing.

To overcome the drawbacks of single-layered wound dressings, bilayer dressings are now introduced as an alternative to achieve effective and long-term treatment. Here, a bilayer dressing composed of electrospun nanofibers in the bottom layer (BL) and a sponge structure as the top layer (TL) is presented. Hydrophilic poly(acrylic acid) (PAAc)-honey (Hny) with interconnected pores of 76.04 µm was prepared as the TL and keratin (Kr), Hny, and vascular endothelial growth factor (VEGF) were prepared as the BL. VEGF indicates a gradual release over 7 days, promoting angiogenesis, as proven by the chick chorioallantoic membrane assay and in vivo tissue histomorphology observation. Additionally, the fabricated dressing material indicated a satisfactory tensile profile, cytocompatibility for human keratinocyte cells, and the ability to promote cell attachment and migration. The in vivo animal model demonstrated that the full-thickness wound healed faster when it was covered with PAAc-Hny/Hny-Kr-VEGF than in other groups. Additionally, faster blood vessel formation, collagen synthetization, and epidermal layer generation were also confirmed, which have proven efficient healing acceleration in wounds treated with synthesized bilayer dressings. Our findings indicated that the fabricated material can be promising as a functional wound dressing.

Efficacy of adjunctive topical liposomal clarithromycin on systemic Glucantime in Old World cutaneous leishmaniasis: a pilot clinical study.

Aim: This study aimed to investigate the effects of topical liposomal clarithromycin in combination with meglumine antimoniate (Glucantime®) on cutaneous leishmaniasis (CL) lesions. Methods: This pilot, randomized, double-blinded clinical trial was conducted on patients with CL lesions. Patients were randomly assigned to two groups: the first group received liposomal clarithromycin in combination with Glucantime for 28 days, while the second group received Glucantime and a placebo. Afterward, patients were followed up at 1.5, 3, and 6 months after treatment initiation and were evaluated for recovery time, induration, and size of the lesions. Results: Sixty patients with CL lesions were divided into two separate groups with 30 members each and were examined. Within-group analysis revealed that recovery time in the clarithromycin group was 26.65 ± 5.12 days, while in the placebo group, it was 32.84 ± 24.43, which was statistically insignificant (p = 0.18). Lesion size comparison in the first and last follow-ups reduced in both groups: 7.73 ± 4.31 to 0.48 ± 0.50 in the clarithromycin group (p = 0.006) and 5.47 ± 5.83 to 0.76 ± 0.88 in the placebo group (p = 0.03). Moreover, the size of lesions in the intervention group was significantly reduced compared to that in the placebo group (p = 0.02). Recognizable induration reduction was observed in the clarithromycin group (2.60 ± 0.77 to 1.0 ± 0.00). No adverse effects attributable to clarithromycin were reported. Conclusion: The administration of liposomal clarithromycin in combination with systemic Glucantime had a significant beneficial effect on reducing lesion size in leishmaniasis. Further studies on larger populations are recommended. Systematic Review Registration: https://www.irct.ir/trial/46611.

Enhancement of the anti-microbial activity of Mentha spicata essential oil on storage by glycerosomes.

Mentha spicata essential oil (EO) is isolated from the aerial parts of Mentha spicata L. with pronounced antibacterial effects as food preservative in food industry. Nevertheless, its application in the clinical industry and food is significantly restricted by its poor water solubility and physicochemical instability. Glycerosomes of this EO were prepared to enhance its anti-microbial stability. The EO was encapsulated in the glycerosomes and characterized for its physical properties. The optimized EO-loaded glycerosomes displayed entrapment efficiency of 93.2 ± 7.5%, release efficiency of 75.4 ± 6.1%, the particle size of 276 nm, and zeta potential of - 30.4 mV. Scanning electron microscopy (SEM) image showed spherical morphology of the glycerosomes. EO release from optimized formulation of glycerosomes best fitted with a first-order kinetic model. Compared with free EO, EO-loaded glycerosomes showed better storage stability. The results indicated that the incorporation of EO in glycerosomes possessed sustained release properties and significantly enhanced antibacterial effects in storage.

Mupirocin loaded core-shell pluronic-pectin-keratin nanofibers improve human keratinocytes behavior, angiogenic activity and wound healing.

In the current study, a core-shell nanofibrous wound dressing based on Pluronic-F127 (F127) containing 2 wt% mupirocin (Mup) core and pectin (Pec)-keratin (Kr) shell was fabricated through coaxial electrospinning technique, and the blended nanofibers were also fabricated from the same materials. The fiber diameter and specific surface area of the blended nanofibers were about 101.56 nm and 20.16 m2/g, while for core-shell nanofibers they were about 97.32 nm and 25.26 m2/g, respectively. The resultant blended and core-shell nanofibers experienced a degradation of 27.65 % and 32.28 % during 7 days, respectively. The drug release profile of core-shell nanofibers revealed a sustained release of Mup over 7 days (87.66 %), while the blended F127-Pec-Kr-Mup nanofibers had a burst release within the first few hours (89.38 % up to 48 h) and a cumulative release of 91.36 % after 7 days. Due to the controlled release of Mup, the core-shell structure significantly improved the human keratinocytes behavior, angiogenic potential and wound healing in a rat model compared to the blended structure. In conclusion, the F127-Mup/Pec-Kr core-shell nanofibrous wound dressing appears to be a promising candidate for the prevention of infection, and can potentially accelerate the recovery and healing of chronic and ischemic wounds.

Incorporation of graphene oxide as a coupling agent in a 3D printed polylactic acid/hardystonite nanocomposite scaffold for bone tissue regeneration applications.

3D printing fabrication has become a dominant approach for the creation of tissue engineering constructs as it is accurate, fast, reproducible and can produce patient-specific templates. In this study, 3D printing is applied to create nanocomposite scaffold of polylactic acid (PLA)/hardystonite (HT)-graphene oxide (GO). GO is utilized as a coupling agent of alkaline treated HT nanoparticles within PLA matrix. The addition of HT-GO nanoparticles of up to 30 wt% to PLA matrix was found to increase the degradability from 7.33 ± 0.66 to 16.03 ± 1.47 % during 28 days. Also, the addition of 20 wt% of HT-GO nanoparticles to PLA scaffold (PLA/20HTGO sample) significantly increased the compressive strength (from 7.65 ± 0.86 to 14.66 ± 1.01 MPa) and elastic modulus (from 94.46 ± 18.03 to 189.15 ± 10.87 MPa). The apatite formation on the surface of nanocomposite scaffolds in simulated body fluid within 28 days confirmed the excellent bioactivity of nanocomposite scaffolds. The MG63 cell adhesion and proliferation and, also, the rat bone marrow mesenchymal stem cells osteogenic differentiation were highly stimulated on the PLA/20HTGO scaffold. According to the sum of results obtained in the current study, the optimized PLA/20HTGO nanocomposite scaffold is highly promising for hard tissue engineering applications.

An antibacterial Multi-Layered scaffold fabricated by 3D printing and electrospinning methodologies for skin tissue regeneration.

A multi-layered scaffold can mimic the hierarchical structure of the skin, accelerate the wound healing, and protect the skin against contamination and infection. In this study, a three-layered (3L) scaffold was manufactured through a combination of 3D printing and electrospinning technique. A top layer of polyurethane (PU) nanofibrous coating for the prevention of micro-organism penetration was created through electrospining. The middle layer was prepared through the 3D printing of Pluronic F127-quaternized chitosan-silver nitrate nanoparticles (F127-QCS-AgNO3), as the porous absorbent and antibacterial layer. A bottom layer of core-shell nanofibrous structure of F127-mupirocin/pectin-keratin (F127-Mup/Pec-Kr) for tissue regeneration and enable antibacterial activity was coated onto the middle layer. A range of techniques were applied to fully characterize the resultant structure. The average tensile strength and elastic modulus of the 3L scaffold were measured as 0.65 ± 0.08 MPa and 9.37 ± 2.33 MPa, respectively. The release of Ag ions, mupirocin (Mup), and the antibacterial activity of the dressings was investigated. According to the results, the highest rate of cell adhesion and viability, and angiogenic potential among the studied samples were related to the 3L scaffold, which was also found to significantly accelerate the wound healing.

Anti HER-2 aptamer functionalized gold nanoparticles of dasatinib for targeted chemo-radiotherapy in breast cancer cells.

In the present study, gold nanoparticles functionalized with anti HER-2 aptamer were designed for effective targeted delivery of dasatinib (DSB) to breast cancer cells. Anti HER-2 aptamer attached to porous or plain gold nanoparticles were compared for dasatinib delivery. Activated drug with succinic anhydride and L-cysteine linker was used for conjugation of DSB to gold nanoparticles. The loading efficiency of the activated drug on plain and porous gold nanoparticles was 52 and 68 %, respectively, which was significantly more than the loading of free DSB in gold nanoparticles (1-2.5 %). The anti HER-2 aptamer was conjugated to porous gold nanoparticles loaded with the activated drug. Various characterization techniques such as FESEM, TEM, AFM, zeta potential and ICP-MS were used to confirm the binding of the drug to gold nanoparticles. 1HNMR and FTIR spectroscopic analyses were employed to examine the structural characteristics of the conjugated drug. These analytical techniques confirmed the successful incorporation of succinyl and thiol groups onto the drug molecule. The amount of aptamer binding to different types of gold nanoparticles was obtained from the intensity of the light emitted from the bands observed in electrophoresis gel and due to the presence of porosity in porous gold nanoparticles, the amount of aptamer conjugation on porous gold nanoparticles increased compared to plain ones. Cell cytotoxicity and cellular uptake were evaluated by MTT assay and TEM in BT-474 and MCF-7 cells. Aptamer-functionalized porous gold nanoparticles containing activated dasatinib showed higher cytotoxicity and cellular uptake than modified DSB-loaded nanoparticles and un-activated DSB. The combination of radiation therapy with the modified dasatinib attached to porous gold nanoparticles and aptamer demonstrated a notable reduction in the IC50 values for both the BT-474 and MCF-7 cell lines. Specifically, the IC50 value for the BT-474 cells decreased from 6.95 µM (for unmodified dasatinib) to 2.57 µM, while for the MCF-7 cells, it decreased from 13.97 µM to 8.57 µM. These findings indicate a significant improvement in the efficacy of the modified dasatinib compared to its unmodified counterpart when used in conjunction with radiation therapy.