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In this study, modified kappa-carrageenan/pectin hydrogel patches were fabricated for treatment of buccal fungal infections. For this purpose, kappa-carrageenan-g-acrylic acid was modified with different thiolated agents (L-cysteine and 3-mercaptopropionic acid), and the thiol content of the resulting modified kappa-carrageenan was confirmed by elemental analyzer. Then, the hydrogel patches were fabricated, and characterized by Fourier-transform infrared spectroscopy, thermogravimetric analysis, ex vivo mucoadhesion test, and swelling behavior. Triamcinolone acetonide was added either directly or by encapsulating within the poly(lactic-co-glycolic acid) nanoparticles. The release amount of the drug from the directly loaded patch was 7.81 mg/g polymer, while it was 3.28 mg/g polymer for the encapsulated patch with the same content at 7 hr. The hydrogel patches had no cytotoxicity by cell culture studies. Finally, the drug loaded hydrogel patches were demonstrated antifungal activity against Aspergillus fumigatus and Aspergillus flavus. These results provide that the novel modified kappa-carrageenan and pectin based buccal delivery system has promising antifungal property, and could have advantages compared to conventional buccal delivery systems. WOS:000723711600001 34846796 Q2

Layered double hydroxides (LDHs) offer unique source of inspiration for design of bone mimetic biomaterials due to their superior mechanical properties, drug delivery capability and regulation cellular behaviors, particularly by divalent metal cations in their structure. Three-dimensional (3D) bioprinting of LDHs holds great promise as a novel strategy thanks to highly tunable physiochemical properties and shear-thinning ability of LDHs, which allow shape fidelity after deposition. Herein, we introduce a straightforward strategy for extrusion bioprinting of cell laden nanocomposite hydrogel bioink of gelatin methacryloyl (GelMA) biopolymer and LDHs nanoparticles. First, we synthesized LDHs by co-precipitation process and systematically examined the effect of LDHs addition on printing parameters such as printing pressure, extrusion rate, printing speed, and finally bioink printability in creating grid-like constructs. The developed hydrogel bioinks provided precise control over extrudability, extrusion uniformity, and structural integrity after deposition. Based on the printability and rheological analysis, the printability could be altered by controlling the concentration of LDHs, and printability was found to be ideal with the addition of 3 wt % LDHs. The addition of LDHs resulted in remarkably enhanced compressive strength from 652 kPa (G-LDH0) to 1168 kPa (G-LDH3). It was shown that the printed nanocomposite hydrogel scaffolds were able to support encapsulated osteoblast survival, spreading, and proliferation in the absence of any osteoinductive factors taking advantage of LDHs. In addition, cells encapsulated in G-LDH3 had a larger cell spreading area and higher cell aspect ratio than those encapsulated in G-LDH0. Altogether, the results demonstrated that the developed GelMA/LDHs nanocomposite hydrogel bioink revealed a high potential for extrusion bioprinting with high structural fidelity to fabricate implantable 3D hydrogel constructs for repair of bone defects. WOS:000865405500001 Q2

In this research, the effect of thiol functional groups on bovine serum albumin (BSA)/chitosan (Chi) based buccal mucoadhesive patch was investigated. Thiolated BSA (BSA-SH) was prepared via 2-mercaptoethanol. FTIR and 1H NMR results confirmed that BSA-SH was synthesized successfully. The buccal mucoadhesive patches were fabricated by the solvent casting method. Following the structural characterization of BSA/Chi and BSA-SH/Chi buccal patches, the mechanical characterization was performed by tensile tests. The drug release from triam- cinolone acetonide (TR) loaded buccal patches was evaluated in-vitro in simulated salivary. According to the ex- vivo buccal adhesion experiments, the mechanical and mucoadhesion properties of BSA-SH/Chi buccal patch had improved compared to BSA/Chi buccal patch. The total cumulative TR permeated after 12 h was higher for BSA- SH/Chi than BSA/Chi buccal patches. The developed mucoadhesive buccal patches were found to be biocom- patible in vitro. To conclude, the thiolated BSA-SH/Chi buccal adhesive patch is a promising biomaterial for a satisfied drug delivery, which provides advantages for various oral applications. 2-s2.0-85132367698

Despite various strategies have been proposed to accelerate bone regeneration, the treatment of bone defects in critical size still remains a clinical challenge. In this study, we fabricated nanocomposite gelatin methacryloyl (GelMA)/nanosilicate (NS) hydrogels for the delivery of dexamethasone (DEX), and systematically investigated their performance in drug delivery for bone repair. Nanocomposite hydrogels were fabricated by mold casting, and exposed to ultraviolet (UV) light to induce covalent crosslinking. Afterwards, we conducted a systematic characterization study to determine the effects of varying NS concentration, GelMA methacrylation degree and UV exposure time on mechanical, structural, and drug release behaviors of nanocomposite hydrogels. In particular, the higher methacrylation degree of GelMA, longer UV exposure and the presence of NS exhibited gradually enhanced mechanical properties. For instance, the compressive strengths of nanocomposite hydrogels containing 0% (w/v) NS (G0NS120) and 3% (w/v) NS (G3NS120) at 120 s of UV exposure were 194.816 kPa–367.284 kPa (p < 0.001), respectively. Similarly, they exhibited higher swelling ratio (%) and slower degradation rate (%) with longer UV exposure and increased NS amount. Nanocomposite hydrogels revealed slower drug release rate due to longer UV exposure and increased NS amount. At day 14 of the release study, 99.53% and 60.687% of DEX were released from G0NS120 and G3NS120, respectively. Particularly, the nanocomposite GelMA/ NS hydrogels supported osteoblast adhesion well, and NS and DEX exhibited synergistic effect on osteoblast proliferation with 5.01 fold increase after 7 days of culture. Our results clearly showed that GelMA/NS nanocomposite hydrogels with tunable physiochemical and drug carrier properties could provide a favorable option for accelerating bone repair. Q2

Sutures, staples, clips, and skin closure strips are used as the gold standard to close wounds after an injury. In spite of being the present standard of care, the utilization of these conventional methods is precarious amid complicated and sensitive surgeries such as vascular anastomosis, ocular surgeries, nerve repair, or due to the high-risk components included. Tissue adhesives function as an interface to connect the surfaces of wound edges and prevent them from separation. They are fluid or semi-fluid mixtures that can be easily used to seal any wound of any morphology-uniform or irregular. As such, they provide alternatives to new and novel platforms for wound closure methods. In this review, we offer a background on the improvement of distinctive tissue adhesives focusing on the chemistry of some of these products that have been a commercial success from the clinical application perspective. This review is aimed to provide a guide to-ward the innovation of tissue bioadhesive materials and their associated biomedical applications. Published by Elsevier Ltd.

In the last decade, 3D-bioprinting has attracted attention due to its capability to produce complex scaffolds. The selection of suitable biomaterials for the bioink design is very important for the success of 3D-bioprinting. In this study, chitosan and gelatin were chemically modified into methacrylated chitosan (ChiMA) and methacrylated gelatin (GelMA) with the methacrylic anhydride in order to obtain crosslinking points on the polymeric backbone. The eligible bioinks were formulated with the layered double hydroxide nanoparticles (LDHs). The effect of changing the amount of LDHs on the printability of the bioinks was evaluated by using rheological analysis and printability test with the extrusion-based 3D-bioprinting. The bioinks were crosslinked under UV light. Mechanical, swelling, degradation properties, and cell-adhesion behaviors of the obtained ChiMA/GelMA nanohybrid scaffolds containing LDHs were investigated. Based on the rheology and the printing results, ChiMA/GelMA nanohybrid scaffold containing 5% LDHs (ChiMA-G5) was found to be the optimal bioink. Notably, compression strength, elongation at break, and elastic modulus of ChiMA-G5 scaffold were higher than neat and other ChiMA/GelMA scaffolds. In vitro cell culture studies showed that LDHs do not have any negative effects. These findings indicate that the developed ChiMA-G5 bioink has great potential as a bioink to utilize for tissue engineering applications. WOS:000702971700001 Q2

Current implantable materials are limited in terms of function as native tissue, and there is still no effective clinical treatment to restore articular impairments. Hereby, a functionalized polyacrylamide (PAAm)-alginate (Alg) Double Network (DN) hydrogel acting as an articular-like tissue is developed. These hydrogels sustain their mechanical stability under different temperature (+4 degrees C, 25 degrees C, 40 degrees C) and humidity conditions (60% and 75%) over 3 months. As for the functionalization, transforming growth factor beta-3 (TGF-beta 3) encapsulated (NPTGF-beta 3) and empty poly(lactide-co-glycolide) (PLGA) nanopartides (PLGA NPs) are synthesized by using microfluidic plat-form, wherein the mean particle sizes are determined as 81.94 +/- 92 nm and 126 +/- 4.52 nm with very low poly-dispersity indexes (PDI) of 0.194 and 0.137, respectively. Functionaliza lion process of PAAm-Alg hydrogels with ester-end PLGA NPs is confirmed by MR analysis, and higher viscoelastidty is obtained for functionalized hydrogels. Moreover, cartilage regeneration capability of these hydrogels is evaluated with in vitro and in vivo experiments. Compared with the PAAm-Alg hydrogels, functionalized formulations exhibit a better cell viability. Histological staining, and score distribution confirmed that proposed hydrogels significantly enhance regeneration of cartilage in rats due to stable hydrogel matrix and controlled release of TGF-beta 3. These findings demonstrated that PAAm-Alg hydrogels showed potential for cartilage repair and clinical application. (C) 2021 Elsevier B.V. All rights reserved., Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [117M843]; National Research Founda-tion of KoreaNational Research Foundation of Korea [2017K2A9A1A06037807], This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) under grant number 117M843. Y.-W.KimandJ.-Y.Sun were supported under the framework of international cooperation program managed by the National Research Founda-tion of Korea (2017K2A9A1A06037807, FY2017).

Wound repair is a complex process that has not been entirely understood. It can conclude in several irregularities. Hence, designing an appropriate wound dressing that can accelerate the healing period is critical. Infections, a major obstacle to wound repair, cause an elevated inflammatory responses and result in ultimate outcome of incomplete and prolonged wound repair. To overcome these shortcomings, there is a growing requirement for antibacterial wound dressings. Dressings with antibacterial activities and multifunctional behaviors are highly anticipated to avoid the wound infection for successful healing. The aim of this review is not only to concentrate on the importance of antibacterial dressings for wound healing applications but also to discuss recent studies and some future perspectives about antibacterial wound dressings.

An approach for cancer treatment is modulation of tumor microenvironment. Based on the role of extracellular matrix in cell modulation, fabrication of textured materials mimicking extracellular matrix could provide novel opportunities such as determining cancer cell behaviour. With this background, in this work, we have fabricated doxorubicin hydrochloride loaded nanotextured films which promote topographical attachment of cancer cells to film surface, and eliminate cells by release of the anti-cancer drug encapsulated within the films. These films are designed to be placed during surgical removal of the tumor with the intent to prevent ovarian cancer recurrence by capturing cancer cell residuals. With this aim, hemispherical protrusion shaped surface textures were acquired using colloidal lithography technique using 280 nm, 210 nm or 99 nm polystyrene particles. Once moulds were formed, nanotextured films were obtained by casting water-in-oil stable polycaprolactone emulsions encapsulating doxorubicin hydrochloride. Films were then characterized, and evaluated as drug delivery systems. According to results, we found that template morphologies were successfully transferred to films by atomic force microscopy studies. Hydrophilic surfaces were formed with contact angle values around 40 degrees.In-vitrodrug release studies indicated that nanotextured films best fit into the Higuchi model, and similar to 30% of the drug is released from the films within 60 days. Cell culture results indicated increases in the attachment and viability of human ovarian cancer cells to nanotextured surfaces, particularly to the film fabricated using 99 nm particles. Our results demonstrated that delivery of anti-cancer drugs by use of nanotextured materials could be efficient in cancer therapy, and may offer new possibilities for cancer treatment.

An amphiphilic core/shell-type polymer-based drug carrier system (HPAE- PCL-b-MPEG), composed of hyperbranched poly(aminoester)-based polymer (HPAE) as the core building block and poly(ethylene glycol)-b-poly(epsilon-caprolactone) diblock polymers (MPEG-b-PCL) as the shell building block, was designed. The synthesized polymers were characterized with FTIR, H-1 NMR, C-13 NMR, and GPC analysis. Monodisperse HPAE-PCL-b-MPEG nanoparticles with dimensions of

Oxaceprol is well-defined therapeutic agent as an atypical inhibitor of inflammation in osteoarthritis. In the present study, we aimed to develop and characterize oxaceprol-loaded poly-lactide-co-glycolide (PLGA) nanoparticles for intra-articular administration in osteoarthritis. PLGA nanoparticles were prepared by double-emulsion solvent evaporation method. Meanwhile, a straightforward and generally applicable high performance liquid chromatography method was developed, and validated for the first time for the quantification of oxaceprol. To examine the drug carrying capacity of nanoparticles, varying amount of oxaceprol was entrapped into a constant amount of polymer matrix. Moreover, the efficacy of drug amount on nanoparticle characteristics such as particle size, zeta potential, morphology, drug entrapment, and in vitro drug release was investigated. Nanoparticle sizes were between 229 and 509 nm for different amount of oxaceprol with spherical smooth morphology. Encapsulation efficiency ranged between 39.73 and 63.83% by decreasing oxaceprol amount. The results of Fourier transform infrared and DSC showed absence of interaction between oxaceprol and PLGA. The in vitro drug release from these nanoparticles showed a sustained release of oxaceprol over 30 days. According to cell culture studies, oxaceprol-loaded nanoparticles had no cytotoxicity with high biocompatibility. This study was the first step of developing an intra-articular system in the treatment of osteoarthritis for the controlled release of oxaceprol. Our findings showed that these nanoparticles can be beneficial for an effective treatment of osteoarthritis avoiding side effects associated with oral administration. Marmara University Scientific Research Projects Coordination UnitMarmara University [SAG-A-120613-0234] Marmara University Scientific Research Projects Coordination Unit, Grant/Award Number: SAG-A-120613-0234 WOS:000508046800001 31958153 Q2

Bone nonunion may occur when the fracture is unstable, or blood supply is impeded. To provide an effective treatment for the healing of nonunion defects, we introduce an injectable osteogenic hydrogel that can deliver cells and vasculogenic growth factors. We used a silicate-based shear-thinning hydrogel (STH) to engineer an injectable scaffold and incorporated polycaprolactone (PCL) nanoparticles that entrap and release vasculogenic growth factors in a controlled manner. By adjusting the solid composition of gelatin and silicate nanoplatelets in the STH, we defined optimal conditions that enable injection of STHs, which can deliver cells and growth factors. Different types of STHs could be simultaneously injected into 3D constructs through a single extrusion head composed of multiple syringes and needles, while maintaining their engineered structure in a continuous manner. The injected STHs were also capable of filling any irregularly shaped defects in bone. Osteogenic cells and endothelial cells were encapsulated in STHs with and without vasculogenic growth factors, respectively, and when co-cultured, their growth and differentiation were significantly enhanced compared to cells grown in monoculture. This study introduces an initial step of developing a new platform of shape-tunable materials with controlled release of angiogenic growth factors by utilizing PCL nanoparticles.

The skin is the largest and most exposed organ in the human body. Not only it is involved in numerous biological processes essential for life but also it represents a significant endpoint for the application of pharmaceuticals. The area of in vitro skin tissue engineering has been progressing extensively in recent years. Advanced in vitro human skin models strongly impact the discovery of new drugs thanks to the enhanced screening efficiency and reliability. Nowadays, animal models are largely employed at the preclinical stage of new pharmaceutical compounds development for both risk assessment evaluation and pharmacokinetic studies. On the other hand, animal models often insufficiently foresee the human reaction due to the variations in skin immunity and physiology. Skin-on-chips devices offer innovative and state-of-the-art platforms essential to overcome these limitations. In the present review, we focus on the contribution of skin-on-chip platforms in fundamental research and applied medical research. In addition, we also highlighted the technical and practical difficulties that must be overcome to enhance skin-on-chip platforms, e.g. embedding electrical measurements, for improved modeling of human diseases as well as of new drug discovery and development.

Peripheral nerve gaps exceeding 1 cm require a bridging repair strategy. Clinical feasibility of autogenous nerve grafting is limited by donor site comorbidity. In this study we investigated neuroregenerative efficacy of autogenous vein grafts implanted with tissue fragments from distal nerve in combination with vascular endothelial growth factor (VEGF) or mesenchymal stem cells (MSCs) in repair of rat peripheral nerve defects. Six-groups of Sprague-Dawley rats (n = 8 each) were evaluated in the autogenous setting using a 1.6 cm long peroneal nerve defect: Empty vein graft (group 1), Nerve graft (group 2), Vein graft and nerve fragments (group 3), Vein graft and nerve fragments and blank microspheres (group 4), Vein graft and nerve fragments and VEGF microspheres (group 5), Vein graft and nerve fragments and MSCs (group 6). Nerve fragments were derived from distal segment. Walking track analysis, electrophysiology and nerve histomorphometry were performed for assessment. Peroneal function indices (PFI), electrophysiology (amplitude) and axon count results for group 2 were -9.12 ± 3.07, 12.81 ± 2.46 mV, and 1697.88 ± 166.18, whereas the results for group 5 were -9.35 ± 2.55, 12.68 ± 1.78, and 1566 ± 131.44, respectively. The assessment results did not reveal statistical difference between groups 2 and 5 (P > 0.05). The best outcomes were seen in group 2 and 5 followed by group 6. Compared to other groups, poorest outcomes were seen in group 1 (P ≤ 0.05). PFI, electrophysiology (amplitude) and axon count results for group 1 were -208.82 ± 110.69, 0.86 ± 0.52, and 444.50 ± 274.03, respectively. Vein conduits implanted with distal nerve-derived nerve fragments improved axonal regeneration. VEGF was superior to MSCs in facilitating nerve regeneration. © 2015 Wiley Periodicals, Inc. Microsurgery 36:578-585, 2016.

Stimuli-responsive porous polymer materials have promising biomedical application due to their ability to trap and release biomacromolecules. In this work, a class of highly porous electrospun fibers is designed using polylactide as the polymer matrix and poly(ethylene oxide) as a porogen. Carbon nanotubes (CNTs) with different concentrations are further impregnated onto the fibers to achieve self-sealing functionality induced by photothermal conversion upon light irradiation. The fibers with 0.4 mg mL−1 of CNTs exhibit the optimum encapsulation efficiency of model biomacromolecules such as dextran, bovine serum albumin, and nucleic acids, although their photothermal conversion ability is slightly lower than the fibers with 0.8 mg mL−1 of CNTs. Interestingly, reversible reopening of the surface pores is accomplished with the degradation of PLA, affording a further possibility for sustained release of biomacromolecules after encapsulation. Effects of CNT loading on fiber morphology, structure, thermal/mechanical properties, degradation, and cell viability are also investigated. This novel class of porous electrospun fibers with self-sealing capability has great potential to serve as an enabling strategy for trapping/release of biomacromolecules with promising applications in, for example, preventing inflammatory diseases by scavenging cytokines from interstitial body fluids.

Nanotechnology offers significant potential in regenerative medicine, specifically with the ability to mimic tissue architecture at the nanoscale. In this perspective, we highlight key achievements in the nanotechnology field for successfully mimicking the composition and structure of different tissues, and the development of bio-inspired nanotechnologies and functional nanomaterials to improve tissue regeneration. Numerous nanomaterials fabricated by electrospinning, nanolithography and self-assembly have been successfully applied to regenerate bone, cartilage, muscle, blood vessel, heart and bladder tissue. We also discuss nanotechnology-based regenerative medicine products in the clinic for tissue engineering applications, although so far most of them are focused on bone implants and fillers. We believe that recent advances in nanotechnologies will enable new applications for tissue regeneration in the near future.

Poly(D,L-lactide-co-glycolide) (PLGA) is the most frequently used biodegradable polymer for developing nano/ microparticles encapsulating therapeutic drugs in controlled release (CR) applications. PLGA based drug delivery devices have several advantages over the conventional devices. One of the advantage is the extended release rates of drugs up to days, weeks or months. Other reasons for the widespread use of PLGA are its biodegradability, its biocompatibility, and the fact that PLGA has been approved by FDA (Food and Drug Administration). Numerous active pharmaceutical ingredients such as anticancer drugs, analgesics, antibiotics and macromolecular drugs such as proteins, peptides, genes, vaccines, antigens, human growth factors, vascular endothelial growth factors etc., are successfully incorporated into PLGA or PLGA based drug delivery devices. As a result, these systems in general can be used to provide targeted (cellular or tissue) delivery of drugs, which localized effect represents also an important benefit. They improve bioavailability, sustain release of drugs or solubilize drugs for systemic delivery. Drug delivery using PLGA or PLGA based polymers is an attractive area with various opportunities for further research and developmental work. In this review, physicochemical and biodegradable properties of PLGA and PLGA based drug delivery devices for tissue engineering and regenerative medicine will be presented.

The most commonly used surgical technique for repairing segmental nerve defects is autogenous nerve grafting; however, this method causes donor site morbidity. In this study, we sought to produce prefabricated nerve grafts that can serve as a conduit instead of autologous nerve using a controlled release system created with vascular endothelial growth factor (VEGF)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres. The study was performed in vitro and in vivo. For the in vitro studies, VEGF-loaded PLGA microspheres were prepared. Thirty rats were used for the in vivo studies. Vein grafts were sutured between the tibial and peroneal nerves in all animals. Three groups were created, and an epineural window, partial incision, and microsphere application were performed, respectively. Walking track analysis, morphologic, and electron microscopic assessment were performed at the end of the eight weeks. Microspheres were produced in spherical shapes as required. Controlled release of VEGF was achieved during a 30-days period. Although signs of nerve injury occurred initially in the partial incision groups according to the indexes of peroneal and tibial function, it improved gradually. The index values were not affected in the other groups. There were many myelinated fibers with large diameters in the partial incision and controlled release groups, while a few myelinated fibers that passed through vein graft in the epineural window group. Thereby, prefabrication was carried out for the second and third groups. It was demonstrated that nerve graft can be prefabricated by the controlled delivery of VEGF. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012.

Bu calismada, eczacilarin majistral formulasyonlara olan yaklasimlari, majistral ilaclar konusundaki bilgi duzeyi, bu ilaclari ne kadar dogru hazirladiklari ve hazirlarken karsilastiklari sorunlar ve bu sorunlari cozmede tutumlarini saptamak amaclanmaktadir. Ayrica bu calisma ile son yillarda sikca yazilan majistral receteler hakkinda veriler toplanmasi da hedeflenmistir. Calismada “Eczane Mesul Mudurlerinin Majistral Ilac Hazirlama ile ilgili Bilgi ve Tutumlari” konulu anket, eczane mesul mudurlerine uygulanmistir. Anketi, eczane eczaciligi yapan 54 eczaci tamamlamistir. Anket sonuclarina gore, Calismaya katilan tum eczanelere majistral ilac recetesi geldigi, fakat bu formulasyonlari hazirlarken eczacilarin cesitli sikintilar yasadiklari saptanmistir.