Duganskovsgaard1960

In vitro drug release studies showed that a complete release of lidocaine was achieved within 4 days from the hollow devices, whereas the solid devices enabled sustained drug release for up to 14 days. SLA 3D printing therefore provides a new manufacturing route to produce bladder-retentive drug delivery devices using elastic polymers, and offers a revolutionary and personalised approach for clinical intravesical drug delivery.With the development and progress of science and technology, magnesium and magnesium alloys have attracted more and more researchers' attention because of their excellent biocompatibility. However, rapid degradation rate of magnesium alloy in vivo seriously limits its application (Arthanari et al., n.d.; Cui et al., 2013 [1,2]). In order to solve this problem, the surface modification of Mg-4.0Zn-0.8Sr alloy was adopted in this paper. According to the requirements of orthopedic materials, anodizing coating (AO), silane coating (SA) and chitosan coating (CS) coating were prepared on its surface, and magnesium alloy was prepared into intramedullary nail, and the corrosion resistance and biocompatibility of the corresponding samples was evaluated. The experimental results show that the AO-SA-CS coating sample has higher corrosion resistance, in addition, it also shows good biocompatibility, such as lower hemolysis rate and normal platelet adhesion morphology. After implantation into the femur, the femur of rats recovered well and the kidney tissue was normal.Implant surfaces with cytocompatible and antibacterial properties are extremely desirable for the prevention of implant's infection and the promotion of osseointegration. In this work, both micro-arc oxidation (MAO) and DC magnetron sputtering techniques were combined in order to endow tantalum-based surfaces with osteoblastic cytocompatibility and antibacterial activity. Porous Ta2O5 layers containing calcium (Ca) and phosphorous (P) were produced by MAO (TaCaP) to mimic the bone tissue morphology and chemical composition (Ca/P ratio close to 1.67). Furthermore, zinc (Zn) nanoparticles were deposited onto the previous surfaces by DC magnetron sputtering without or with an additional thin carbon layer deposited over the nanoparticles (respectively, TaCaP-Zn and TaCaP-ZnC) to control the Zn ions (Zn2+) release. Before osteoblastic cell seeding, the surfaces were leached for three time-points in PBS. All modified samples were cytocompatible. TaCaP-Zn slightly impaired cell adhesion but this was improved in the samples leached for longer immersion times. The initial cell adhesion was clearly improved by the deposition of the carbon layer on the Zn nanoparticles, which also translated to a higher proliferation rate. Both Zn-containing surfaces presented antibacterial activity against S. aureus. The two surfaces were active against planktonic bacteria, and TaCaP-Zn also inhibited sessile bacteria. Attributing to the excellent in vitro performance of the nanostructured Ta surface, with osteoconductive elements by MAO followed by antimicrobial nanoparticles incorporation by magnetron sputtering, this work is clearly a progress on the strategy to develop a new generation of dental implants.The role of Traditional Chinese Medicine (TCM), especially herbs or herbal extracts, in treating diseases has received increasing attention. This review focuses on the use of herbal extracts as signaling molecules and functional materials in the field of orthopedics, biomaterial science and bone tissue engineering strategies. A literature review using both Chinese and English references on herbs and herbal extracts based on TCM theory used in orthopedics and biomaterial science was performed. We discuss the efficacy of herbs, the active extracts from these herbs, the combination of herbal extracts and biomaterials and, finally, the application of herbal extracts to the biomaterials specific to orthopedics. Only a few studies have confirmed the feasibility of applying herbal extracts to biomaterials to improve the role of biomaterials and/or optimize drug delivery and release in orthopedics. In this context, this review reveals a new and promising direction for herbal extracts, where the use of herbal extracts based on TCM systemic treatment, can change the limited modern medicine view of biomaterials as "only for local treatment" when considering its efficacy.The sol-gel method is versatile and one of the well-established synthetic approaches for preparing bioactive glass with improved microstructure. In a successful approach, alkoxide precursors undergo rapid hydrolysis, followed by immediate condensation leading to the formation of three-dimensional gels. On the other hand, a slow kinetics rate for hydrolysis of one or more alkoxide precursors generates a mismatch in the progression of the consecutive reactions of the sol-gel process, which makes it difficult to form homogeneous multicomponent glass products. The amorphous phase separation (APS) into the gel is thermodynamically unstable and tends to transform into a crystalline form during the calcination step of xerogel. In the present study, we report a combined experimental and theoretical method to investigate the stability towards hydrolysis of triethyl phosphate (TEP) and its effects on the mechanism leading to phase separation in 58S bioactive glass obtained via sol-gel route. A multitechnical approach fe precursor source of phosphorus (TEP) in the phase separation, an event commonly observed for these biomaterials.The aim of this work was to develop injectable bone substitutes (IBS) consisting of zoledronic acid (ZOL) and graphene oxide (GO) for the treatment of osteoporosis and metastasis. The powder phase was consisting of tetra calcium phosphate (TTCP), dicalcium phosphate dihyrate (DCPD) and calcium sulfate dihyrate (CSD), while the liquid phase comprised of methylcellulose (MC), gelatin and sodium citrate dihyrate (SC), ZOL and GO. The structural analysis of IBS samples was performed by Fourier Transform Infrared Spectroscopy (FTIR). Injectability, setting time and mechanical strength were investigated. Additionally, in vitro properties of synthesized IBS were analyzed by means of bioactivity, ZOL release, degradation, pH variation, PO43- ion release and cell studies. Overall, all IBS exhibited excellent injectability results with no phase separation. The setting time of the IBS was prolonged with ZOL incorporation while the prolonging effect decreased with GO incorporation. The mechanical properties decreased with ZOL addition and increased with the incorporation of GO. The maximum compressive strength was found as 25.73 MPa for 1.5GO0ZOL incorporated IBS. In vitro results showed that ZOL and GO loaded IBS also revealed clinically suitable properties with controlled release of ZOL, pH value and PO43- ions. In in vitro cell studies, both the inhibitory effect of ZOL and GO loaded IBS on MCF-7 cells and proliferative effect on osteoblast cells were observed. Moreover, the prepared IBS led to proliferation, differentiation and mineralization of osteoblasts. The results are encouraging and support the conclusion that developed IBS have promising physical and in vitro properties which needs to be further validated by gene expression and in vivo studies.As a paper-like membrane composed of single-walled carbon nanotube (SWCNT), buckypaper possesses high conductivity, ideal flexibility, large surface area, great thermal/chemical stability and biocompatibility, which has manifested its potential as an alternative support material. However, due to the lack of defects, high quality SWCNT synthesized by arc-discharge method is difficult to be modified with metal nanoparticles for electro-catalysis. In this paper, a novel green strategy has been developed to fabricate SWCNT buckypaper decorated with Cu/reduced graphene oxide (Cu/rGO-BP) for the first time, in which graphene oxide functions as the intermediate between SWCNT and Cu nanoparticles. The fabricated Cu/rGO-BP was applied as a flexible electrode for electrochemical glucose detection. The electrode exhibited excellent electro-catalytic activity for glucose oxidation. The sensor based on Cu/rGO-BP performed a high upper limit of linear range (25 mM), which is close to commercial glucose sensors. The proposed strategy for Cu/rGO-BP fabrication can be extended to modify buckypaper with other metal or metal oxide nanoparticles, and thus opens an innovative route to potential practical applications of flexible buckypaper in wearable bioelectronics.Carbon-based quantum dots (CDs) are mainly divided into two sub-groups; carbon quantum dots (CQDs) and graphene quantum dots (GQDs), which exhibit outstanding photoluminescence (PL) properties, low toxicity, superior biocompatibility and facile functionalization. Regarding these features, they have been promising candidates for biomedical science and engineering applications. In this work, we reviewed the efforts made to modify these zero-dimensional nano-materials to obtain the best properties for bio-imaging, drug and gene delivery, cancer therapy, and bio-sensor applications. Five main surface modification techniques with outstanding results are investigated, including doping, surface functionalization, polymer capping, nano-composite and core-shell structures, and the drawbacks and challenges in each of these methods are discussed.Silica incorporation into biomaterials, such as Bioglass and Si-substituted calcium phosphate ceramics has received significant attention in bone tissue engineering over the last few decades. This study aims to explore the dissolution behaviour of natural biosilica isolated from a freshwater diatom, Cyclotella meneghiniana, that has been incorporated into 3D printed poly (DL-lactide -co - glycolide) (PDLGA) scaffolds using extrusion and additive manufacturing. In the study, two different dry weight percentage (1 wt% & 5 wt%) of diatom-silica were incorporated into PDLGA scaffolds that were then degraded in phosphate buffered saline (PBS) cell free media. In addition, pure PDLGA scaffolds and 5 wt% Bioglass scaffolds were used as control groups. The degradation study was performed over 26-weeks. The release rate of Si4+ ions from diatom-PDLGA scaffolds was found to increase exponentially with respect to time. The compressive strength of scaffolds was also measured with the Diatom-PDLGA scaffolds found to maintain their strength for longer than either pure PDLGA scaffolds or 5 wt% Bioglass scaffolds. 13C NMR data showed that diatom biosilica containing scaffolds had less degradation than pure or bioglass-containing scaffolds at comparable time-points. Overall, the Diatom-PDLGA scaffolds were found to have more desirable physiochemical properties for bone repair compared to Bioglass.Open cell polyurethane foams are often used as cancellous bone surrogates because of their similarities in morphology and mechanical response. In this work, open cell polyurethane foams of three different densities are characterized from morphometric and mechanical perspectives. The analysis of micro-computed tomography images has revealed that the high density foams present the greatest inhomogeneities. Those inhomogeneities promoted the failure location. We have used the finite element models as a tool to estimate elastic and failure properties that can be used in numerical modeling. Furthermore, we have assessed the anisotropic mechanical response of the foams, whose differences are related to the morphometric inhomogeneities. We found significant relationships between morphometry and the elastic and failure response. The detailed information about morphometry, elastic constants and strength limits provided in this work can be of interest to researchers and practitioners that often use these polyurethane foams in orthopedic implants and cement augmentation evaluations.Corneal transplantation is currently the only approach to cure corneal blindness. Cell-based strategies that employ corneal endothelial cells (CECs) grown on supporting biomaterials hold great promise as possible alternative therapies for treating corneal endothelial dysfunction. Nevertheless, most biomaterials are used merely because of their robust mechanical properties, providing passive physical support for the transplantation of CEC monolayers. Based on the versatility of curcumin in ophthalmic applications, this study aims to develop a multifunctional scaffold system that can not only support the function and transplantation of CECs but also prevents post-engraftment complications by sustained curcumin release, thus enhancing the long-term success of CEC engraftment. Curcumin-loaded lipid-poly(lactic-co-glycolic acid) (PLGA; Cur@MPs) hybrid microparticles (MPs) fabricated using an oil-in-water single emulsion method are embedded into gelatin-based scaffolds. The anti-inflammatory, antioxidative, and anti-angiogenic potentials of the developed scaffolds and their capacity in supporting CEC monolayer formation are evaluated. The Cur@MPs are capable of promoting CEC proliferation, protecting CECs from oxidative stress-induced cell death via modulating Nrf2/HO-1 signaling axis, suppressing the secretion of pro-inflammatory cytokines by macrophages, and inhibiting the migration and angiogenesis of vascular endothelial cells. By incorporating the Cur@MPs into a thin gelatin membrane, the fabricated scaffold is able to support the growth and organization of CECs into a polygonal morphology with tight junctions. These experimental results demonstrate the potential of the Cur@MPs-loaded gelatin scaffold for actively supporting the survival and function of CEC monolayers after transplantation.Fabrication of extracellular matrix (ECM)-like scaffolds (in terms of structural-functional) is the main challenge in skin tissue engineering. Herein, inspired by macromolecular components of ECM, a novel hybrid scaffold suggested which includes silk/hyaluronan (SF/HA) bio-complex modified by PCP [polyethylene glycol/chitosan/poly(ɛ-caprolactone)] copolymer containing collagen to differentiate human-adipose-derived stem cells into keratinocytes. In followed by, different weight ratios (wt%) of SF/HA (S1100/0, S280/20, S350/50) were applied to study the role of SF/HA in the improvement of physicochemical and biological functions of scaffolds. Notably, the combination of electrospinning-like and freeze-drying methods was also utilized as a new method to create a coherent 3D-network. The results indicated this novel technique was led to ~8% improvement of the scaffold's ductility and ~17% decrease in mean pore diameter, compared to the freeze-drying method. Moreover, the increase of HA (>20wt%) increased porosity to 99%, however, higher tensile strength, modulus, and water absorption% were related to S2 (38.1, 0.32 MPa, 75.3%). More expression of keratinocytes along with growth pattern similar to skin was also observed on S2. This study showed control of HA content creates a microporous-environment with proper modulus and swelling%, although, the role of collagen/PCP as base biocomposite and fabrication technique was undeniable on the inductive signaling of cells. Such a scaffold can mimic skin properties and act as the growth factor through inducing keratinocytes differentiation.Electrochemical sensors have increasingly been linked with terms as modern biomedically effective highly selective and sensitive devices, wearable and wireless technology, portable electronics, smart textiles, energy storage, communication and user-friendly operating systems. The work brings the overview of the current advanced materials and their application strategies for improving performance, miniaturization and portability of sensing devices. It provides the extensive information on recently developed (bio)sensing platforms based on voltammetric, amperometric, potentiometric and impedimetric detection modes including portable, non-invasive, wireless, and self-driven miniaturized devices for monitoring human and animal health. Diagnostics of selected free radical precursors, low molecular biomarkers, nucleic acids and protein-based biomarkers, bacteria and viruses of today's interest is demonstrated.Fabrication of simultaneously robust and superabsorbent gelatin-based hydrogels for biomedical applications still remains a challenge due to lack of locally dissipative points in the presence of large water content. Here, we apply a synthesis strategy through which water absorbency and energy dissipative points are separated, and toughening mechanism is active closely at the crack tip. For this, gelatin-based microgels (GeMs) were synthesized in a way that concentrated supramolecular interactions were present to increase the energy necessary to propagate a macroscopic crack. The microgels were interlocked to each other via both temporary hydrophobic associations and permanent covalent crosslinks, in which the sacrificial binds sustained the toughness due to the mobility of the junction zones and particles sliding. However, chemical crosslinking points preserved the integrity and fast recoverability of the hydrogel. Hysteresis increased strongly with increasing supramolecular interactions within the network. The prepared hydrogels showed energy loss and swelling ratio up to 3440 J. m-3 and 830%, respectively, which was not achievable with conventional network fabrication methods. The microgels were also assessed for their in vivo biocompatibility in a rat subcutaneous pocket assay. Results of hematoxylin and eosin (H&E) staining demonstrated regeneration of the tissue around the scaffolds without incorporation of growth factors. Also, vascularization within the scaffolds was observed after 4 weeks implantation. These results indicate that our strategy is a promising method to manipulate those valuable polymers, which lose their toughness and applicability with increasing their water content.Bone regeneration using bioactive molecules and biocompatible materials is growing steadily with the advent of the new findings in cellular signaling. Bone Morphogenetic Protein (BMP)-9 is a considerably recent discovery from the BMP family that delivers numerous benefits in osteogenesis. The Smad cellular signaling pathway triggered by BMPs is often inhibited by Noggin. However, BMP-9 is resistant to Noggin, thus, facilitating a more robust cellular differentiation of osteoprogenitor cells into preosteoblasts and osteoblasts. This review encompasses a general understanding of the Smad signaling pathway activated by the BMP-9 ligand molecule with its specific receptors. The robust osteogenic cellular differentiation cue provided by BMP-9 has been reviewed from a bone regeneration perspective with several in vitro as well as in vivo studies reporting promising results for future research. The effect of the biomaterial, chosen in such studies as the scaffold or carrier matrix, on the activity of BMP-9 and subsequent bone regeneration has been highlighted in this review. The non-viral delivery technique for BMP-9 induced bone regeneration is a safer alternative to its viral counterpart. The recent advances in non-viral BMP-9 delivery have also highlighted the efficacy of the protein molecule at a low dosage. This opens a new horizon as a more efficient and safer alternative to BMP-2, which was prevalent among clinical trials; however, BMP-2 applications have reported its downsides during bone defect healing such as cystic bone formation.To realize encapsulation of living microbial cells and easily evaluation of cell viability after immobilization, the yeast cells were encapsulated in water soluble PAAm nanofiber by a facile and effective electrospinning technology. Firstly, the conductivity, shear viscosity and surface tension of PAAm/yeast electrospinning solution as a function of mass ratios of yeast/PAAm were investigated to determine the optimum solution condition for electrospinning immobilization. After electrospinning, it is interesting to note that the original ellipsoidal structure of yeast cells turns to oblate spheroid structure. To distinguish immobilization structure from the bead appearing during general electrospinning process, immobilization structure and bead structure were compared and analyzed by FESEM and EDX. Free cell activity, the immediate cell activity after electrospinning and cell activity for seven days storage after immobilization were evaluated by dying methods of CTC and methylene blue, respectively. The results show that encapsulation efficiency maintained at about 40%, and immobilized yeast cells remain active even after seven days storage, which provides a promising application prospect for electrospinning immobilization.There is a great need for tissue engineering constructs with the ability to modulate stem cell behavior. The initial adhesion, growth and differentiation of stem cell are a key strategy in bone tissue engineering and it can be controlled through biomaterial-cell interface. Here we engineered a polycaprolactone/gelatin/bioactive glass (PCL/GT/BG) nanocomposite scaffold coated with Fibronectin (FN) as a potential candidate to aid the bone regeneration process by giving cells a temporary template to grow into. For this purpose, initially BG nanoparticles (nBG) of 70 ± 15 nm were synthesized, characterized and then impregnated into PCL/GT matrix to create a nanocomposite fibrous mesh. An optimized structure was selected based on fiber uniformity, diameter, and the mechanical properties. Cell adhesion, growth, and the expression of osteogenic-related genes as a result of FN tethering, through specific surface interactions, was evaluated. Furthermore, the potential of optimized nanofiberous structure as a drug delivery vehicle for the local release of therapeutic agents was studied by using amoxicillin as a model drug. The release profile revealed that around 70% of drug was released in an hour for non-crosslinked fibers (burst release) followed by a gradual release up to 72 h. The release profile was steadier for crosslinked fibers. The scaffold also showed an antibacterial effect against ubiquitous gram-positive Staphylococcus aureus. The current study provides an insight for future researchers who aim to create nanocomposite materials as multifunctional scaffolds for bone tissue engineering applications.The recently developed additively manufacturing techniques have enabled the fabrication of porous biomaterials that mimic the characteristics of the native bone, thereby avoiding stress shielding and facilitating bony ingrowth. However, aseptic loosening and bacterial infection, as the leading causes of implant failure, need to be further addressed through surface biofunctionalization. Here, we used a combination of (1) plasma electrolytic oxidation (PEO) using Ca-, P-, and silver nanoparticle-rich electrolytes and (2) post-PEO hydrothermal treatments (HT) to furnish additively manufactured Ti-6Al-4V porous implants with a multi-functional surface. The applied HT led to the formation of hydroxyapatite (HA) nanocrystals throughout the oxide layer. This process was controlled by the supersaturation of Ca2+ and PO43- during the hydrothermal process. Initially, the high local supersaturation resulted in homogenous nucleation of spindle-like nanocrystals throughout the surface. As the process continued, the depletion of reactant ions in the outermost surface layer led to a remarkable decrease in the supersaturation degrees. High aspect-ratio nanorods and hexagonal nanopillars were, therefore, created. The unique hierarchical structure of the microporous PEO layer (pore size less then 3 μm) and spindle-like HA nanocrystals ( less then 150 nm) on the surface of macro-porous additively manufactured Ti-6Al-4V implants provided a favorable substrate for the anchorage of cytoplasmic extensions assisting cell attachment and migration on the surface. The results of our in vitro assays clearly showed the important benefits of the HT and the spindle-like HA nanocrystals including a significantly stronger and much more sustained antibacterial activity, significantly higher levels of pre-osteoblasts metabolic activity, and significantly higher levels of alkaline phosphatase activity as compared to similar PEO-treated implants lacking the HT.Developing a transparent substitute with high water permeability and similar mechanical properties to cornea is one of the major challenge in corneal tissue engineering. Here, transparent hybrid films based on silk nanofibrils (SNF)/gelatin methacryloyl (GelMA) are introduced for cornea tissue engineering. The mechanical properties, transparency, degradation rate and swelling ratio of hybrid films could be tuned by modulation the volume ratio of SNF to GelMA. Among them, the optimal SNF/GelMA ratio of 30/70 shows high transparency with a light transmittance of more than 85% in the wet state, hydrophilicity and mechanical properties close to the natural corneal stroma. The elastic modulus of 36.2 ± 7 kPa, the tensile strength of 3.8 ± 1 MPa and the ability to absorb water up to 138 ± 27% are the features of this hybrid membrane. Moreover, incorporation of SNF upon 30 (v/v) % (30S/70G sample) significantly reduces the degradation rate of GelMA (upon 2 times) making it promising for cornea regeneration. Cell culture studies also prove the ability of SNF/GelMA films to support the attachment, spreading and proliferation of stromal cells, depending on the film composition. Noticeably, 30S/70G film significantly promotes cell metabolic activity (2 times) compared to SNF. In addition, 97 ± 2% of the area of this sample is covered with cells after 5 days of culture which is 8 times greater than that of SNF. In summary, the SNF/GelMA film with volume ratio of 30/70 presents desirable mechanical, optical and biological properties making it an attractive candidate for the regeneration of cornea.Dense collagen (DC) gels facilitate the osteoblastic differentiation of seeded dental pulp stem cells (DPSCs) and undergo rapid acellular mineralization when incorporated with bioactive glass particles, both in vitro and subcutaneously in vivo. However, the potential of DC-bioactive glass hybrid gels in delivering DPSCs for bone regeneration in an osseous site has not been investigated. In this study, the efficacies of both acellular and DPSC-seeded DC-S53P4 bioactive glass [(53)SiO2-(23)Na2O-(20)CaO-(4)P2O5, wt%] hybrid gels were investigated in a critical-sized murine calvarial defect. The incorporation of S53P4, an osteostimulative bioactive glass, into DC gels led to its accelerated acellular mineralization in simulated body fluid (SBF), in vitro, where hydroxycarbonated apatite was detected within 1 day. By day 7 in SBF, micro-mechanical analysis demonstrated an 8-fold increase in the compressive modulus of the mineralized gels. The in-situ effect of the bioactive glass on human-DPSCs within DC-S53P4 was evident, by their osteogenic differentiation in the absence of osteogenic supplements. The production of alkaline phosphatase and collagen type I was further increased when cultured in osteogenic media. This osteostimulative effect of DC-S53P4 constructs was confirmed in vivo, where after 8 weeks implantation, both acellular scaffolds and DPSC-seeded DC-S53P4 constructs formed mineralized and vascularized bone matrices with osteoblastic and osteoclastic cell activity. Surprisingly, however, in vivo micro-CT analysis confirmed that the acellular scaffolds generated larger volumes of bone, already visible at week 3 and exhibiting superior trabecular architecture. The results of this study suggest that DC-S53P4 scaffolds negate the need for stem cell delivery for effective bone tissue regeneration and may expedite their path towards clinical applications.A crucial factor in the pathogenesis of orthopedics associated infections is that bacteria do not only colonize the implant surface but also the surrounding tissues. This study aimed to engineer an antimicrobial release coating for stainless steel (SS) surfaces, to impart them with the ability to prevent Staphylococci colonization. Chlorhexidine (CHX) was immobilized using two polydopamine (pDA)-based approaches a one-pot synthesis, where CHX is dissolved together with dopamine before its polymerization; and a two-step methodology, comprising the deposition of a pDA layer to which CHX is immobilized. To modulate CHX release, an additional layer of pDA was also added for both strategies. Immobilization of CHX using a one-step approach yielded surfaces with a more homogenous coating and less roughness than the other strategies. The amount of released CHX was lower for the one-step approach, as opposed to the two-step approach yielding the higher release, which could be decreased by applying an outward layer of pDA. Both one and two-step approaches provided the surfaces with the ability to prevent bacterial colonization of the surface itself and kill most of bacteria in the bulk phase up to 10 days. This long-term antimicrobial performance alluded a stable and enduring immobilization of CHX. In terms of biocompatibility, the amount of CHX released from the one-step approach did not compromise the growth of mammalian cells, contrary to the two-step strategy. Additionally, the few bacteria that managed to adhere to surfaces modified with one-step approach did not show evidence of resistance towards CHX. Overall data underline that one-step immobilization of CHX holds great potential to be further applied in the fight against orthopedic devices associated infections.The uncontrolled parenchymatic bleeding is still a cause of serious complications in surgery and require new effective hemostatic materials. In recent years, numerous chitosan-based materials have been intensively studied for parenchymatic bleeding control but still require to increased safety and effectiveness. The current research is devoted to new hemostatic materials made of natural polymer (chitosan) developed using electrospinning and microwave-assisted methods. Hemostatic performance, biocompatibility, degradation, and in-vivo effectiveness were studied to assess functional properties of new materials. Chitosan-based agents demonstrated considerable hemostatic performance, moderate biodegradation pace and high biocompatibility in vitro. Using the electrospinning-made chitosan-copolymer significantly improved in vivo biocompatibility and degradation of Chitosan-based agents that provides opportunities for its implementation for visceral bleeding management. Chitosan aerogel could be effectively applied in hemostatic patch development due to high antibacterial activity but it is not recommended for visceral application due to moderate inflammatory effect and slow degradation.The cell-extracellular matrix (ECM) interactions are known to have a strong impact on cell behaviors in neural tissues. Due to complex physiology system and limited regenerative capacity of nervous system, neural tissue engineering has attracted attention as a promising strategy. In this study, we designed a hydrogel loaded by poly (lactic-co-glycolic acid) (PLGA) microspheres containing carbon nanotubes (CNT) and the biochemical differentiation factors, as a scaffold, in order to replicate the neural niche for stem cell growth (and/or differentiation). Different formulations from Hyaluronic acid (H), Poloxamer (P), Ethoxy-silane-capped poloxamer (PE), and cross-linked Alginate (Alg) were utilized as an in situ gel structure matrix to mirror the mechanical properties of the ECM of CNS. Subsequently, conductivity, surface morphology, size of microspheres, and CNT dispersion in microsphere were measured using two probes electrical conductometer, scanning electron microscopy (SEM), dynamic light scattering (DLS)f induction factors was found to notably enhance the expression of Sox2-SYP and β-Tubulin III neuronal markers.Biomolecule carrier structures have attracted substantial interest owing to their potential utilizations in the field of bone tissue engineering. In this study, MOF-embedded electrospun fiber scaffold for the controlled release of BMP-6 was developed for the first time, to enrich bone regeneration efficacy. The scaffolds were achieved by first, one-pot rapid crystallization of BMP-6 encapsulated ZIF-8 nanocrystals-as a novel carrier for growth factor molecules- and then electrospinning of the blending solution composed of poly (ε-caprolactone) and BMP-6 encapsulated ZIF-8 nanocrystals. BMP-6 molecule encapsulation efficiency for ZIF-8 nanocrystals was calculated as 98%. The in-vitro studies showed that, the bioactivity of BMP-6 was preserved and the release lasted up to 30 days. The release kinetics fitted the Korsmeyer-Peppas model exhibiting a pseudo-Fickian behavior. The in-vitro osteogenesis studies revealed the superior effect of sustained release of BMP-6 towards osteogenic differentiation of MC3T3-E1 pre-osteoblasts. In-vivo studies also revealed that the sustained slow release of BMP-6 was responsible for the generation of well-mineralized, new bone formation in a rat cranial defect. Our results proved that; MOF-carriers embedded in electrospun scaffolds can be used as an effective platform for bone regeneration in bone tissue engineering applications. The proposed approach can easily be adapted for various growth factor molecules for different tissue engineering applications.Chitosan nanoparticles (CSNPs) have been recently explored as a potential drug carrier to enhance the bioavailability and aqueous solubility of drugs. Curcumin, an antioxidant with a remarkable antiradical scavenging activity was encapsulated in CSNPs to revamp its bioavailability. While changes in the optimal farming condition can induce oxidative stress in the animals, curcumin loaded chitosan nanoparticles (Cur-CSNPs) were amalgamated into shrimp feed pellets to ameliorate its antioxidant content in an attempt to bolster the organisms against oxidative stress. Cur-CSNPs were synthesized in two different concentrations of curcumin as Cur-CSNPs A and B. Characterization of the synthesized Cur-CSNPs revealed asymmetrical nanoparticles with semispherical geometry and a zeta potential ˃50 mV. HPLC studies substantiated encapsulation efficiencies of 77.53% and 80.35% for Cur-CSNPs A and B respectively. DPPH, ABTS and FRAP assays manifested a significant enhancement in the antioxidant property of the Cur-CSNPs fortified feed pellets. This is the first study to investigate and demonstrate the ability of Cur-CSNPs to enhance the antioxidant property of aquaculture feed pellets. These findings substantiate that Cur-CSNPs fortified feed may be applied to reinforce aquaculture animals against oxidative stress.There has been growing interest in recent years in developing multifunctional materials for studying the structure interface in biological systems. In this regard, the multimodal systems, which possess activity in the near-infrared (NIR) region, become even more critical for the possibility of improving examined biotissue depth and, eventually, data analysis. Herein, we engineered bi-modal contrast agents by integrating carbon nanotubes (CNT) and gold nanoparticles (AuNP) around silica microspheres using the Layer-by-Layer self-assembly method. The experimental studies revealed that microspheres with CNT sandwiched between AuNP exhibit strong absorption in the visible and NIR regions and high optoacoustic contrast (OA, also called photoacoustics) and Raman scattering when illuminated with 532 nm and 785 nm lasers, respectively. The developed microspheres demonstrated amplification of the signal in the OA flow cytometry at the laser wavelength of 1064 nm. This finding was further validated with ex vivo brain tissue using a portable Raman spectrometer and imaging with the Raster-scanning OA mesoscopy technique. The obtained data suggest that the developed contrast agents can be promising in applications of localization OA tomography (LOT), OA flow cytometry, and multiplex SERS detection.One of the main problems that remain in the implant industry is poor osseointegration due to bioinertness of implants. In order to promote bioactivity, calcium (Ca), phosphorus (P) and strontium (Sr) were incorporated into a TiO2 porous layer produced by micro-arc oxidation. Ca and P as bioactive elements are already well reported in the literature, however, the knowledge of the effect of Sr is still limited. In the present work, the effect of various amounts of Sr was evaluated and the morphology, chemical composition and crystal structure of the oxide layer were investigated. Furthermore, in vitro studies were carried out using human osteoblast-like cells. The oxide layer formed showed a triplex structure, where higher incorporation of Sr increased Ca/P ratio, amount of rutile and promoted the formation of SrTiO3 compound. Biological tests revealed that lower concentrations of Sr did not compromise initial cell adhesion neither viability and interestingly improved mineralization. However, higher concentration of Sr (and consequent higher amount of rutile) showed to induce collagen secretion but with compromised mineralization, possibly due to a delayed mineralization process or induced precipitation of deficient hydroxyapatite. Ca-P-TiO2 porous layer with less concentration of Sr seems to be an ideal candidate for bone implants.Magnesium and its alloys have been recently used in biomedical applications such as orthopedic implants, whereas the weak corrosion resistance undermines their clinical efficacy. Herein, to address this critical challenge, the preparation of hierarchically structured hydroxyapatite-based coatings was proposed. Compact coatings were fabricated on a Mg alloy through a facile two-step method of chemical deposition of brushite precursor and subsequent hydrothermal conversion. A series of HA-based coatings were obtained with kinetic conversion process with formation mechanism revealed. The hydroxyapatite coating demonstrated the greatest corrosion resistance for Mg in electrochemical and long-term immersion tests, especially against pitting corrosion, attributable to its compact structure, alkaline degradation environment and self-induced growth capacity. The in vitro cytocompatibility and osteoinductivity were dictated. Additionally, anti-corrosion mechanisms were compared among different coating compositions and structures, along with their correlation with cellular response. Our study brings hints for a tailored surface design for resorbable biomedical device applications.At present, cardiovascular stent intervention faces clinical complications such as delayed endothelialization, late thrombosis and restenosis after implantation. In this work, a kind of bifunctional polymer brush-grafted coronary stent with anticoagulant and endothelial functions was developed. First, a block copolymer brush with zwitterionic structure consisting of sulfoethyl methacrylate (SBMA) and glycidyl methacrylate (GMA) was surface-induced grafted onto the surface of bare metal coronary stent by atom transfer radical polymerization. The diethylenetriamine NONOate (DETA NONOate), acted as nitric oxide (NO) donor to promote endothelialization, was then attached to polyglycidyl methacrylate (PGMA) brush by a reactive epoxy group to produce NO. The process of chemical modification and the release behavior of NO were characterized in detail. Moreover, the results of anticoagulant test, cytotoxicity test, endothelial cells (ECs) proliferation test and animal experiment of this bifunctional polymer brush-grafted coronary stent we proposed indicate that the zwitterion modified and NO supplied bifunctional coatings has good anticoagulant property, no cytotoxicity and significant endothelialization effect. This work opens the door to combine biological activity of NO and anticoagulant effect of zwitterions, which has great potential to address post-operative side effects associated with restenosis and late stent thrombosis.Wound dressings are typically used to provide a favorable environment supporting the intricate process of wound healing. This research aims to fabricate and evaluate an electrospun polycaprolactone (EsPCL) membrane coated with various densities of chitosan oligomers (COS) - a biological agent - for application as bioactive wound dressing. Weight calculation was employed to investigate the density of COS coated onto the electrospun PCL membrane. Physicochemical characteristics of the prepared membranes, such as hydrophilicity and mechanical properties were demonstrated and evaluated through standard experimental methods. In vitro assays and mice model were used to investigate the antibacterial activities, cytocompatibility, hemostasis and the in vivo interaction of the membranes. The results showed that COS was coated successfully on the surface of the polymeric membrane, altering its morphology and associated characteristics. The greater concentration of COS led to an increase in the thickness of the membrane, which resulted in stronger antibacterial activities. Moreover, the increase of chitosan oligomers density in the membrane induced faster hemostasis and affected the re-epithelialization and wound healing in mice. Thus, the membrane as a whole and particularly chitosan oligomers were shown to be potential for further studies regarding wound dressing.In this study, hexachlorocyclotriphosphazene (HCCP) and tannic acid (TA) were used at different stoichiometric ratios to synthesize cyclomatrix-type polymeric materials with different surface features and dimensions. Using different reactive ratios, the structure and surface functional groups of the synthesized polymeric particles were explained using Fourier-Transform Infrared Spectroscopic (FTIR), Scanning Electron Microscope (SEM), Energy-dispersive X-ray spectroscopy (EDX), X-ray Photoelectron Spectroscopy (XPS) and Thermogravimetric (TG) analysis techniques. With morphologically fully spherical structure and mean 234.82 ± 49.37 nm dimensions, Phz-TA (41) nanospheres were researched for in vitro biodegradability, antioxidant features, and usability as a drug release system. In vitro biodegradability of Phz-TA (41) nanospheres was investigated at pH = 7.0 and pH = 1.2. Determined to degrade in 8-10 h at these pH values, nanospheres were used for releasing of Rhodamine 6G as a model drug. Due to the rich phenolic structure of the contained tannic acid units, nanospheres were determined to simultaneously have antioxidant features. Thus, this study determined that Phz-TA nanospheres with in vitro biodegradability and antioxidant features are promising polymeric materials for use as a potential drug-carrier in the future.Among various methods, the use of targeting nucleic acid therapy is a promising method for inhibiting gastric cancer (GC) cells' rapid growth and metastasis abilities. In this study, vitamin B12-labeled poly (d,l-lactide-co-glycolide) and polyethylene glycol nanoparticles (PLGA-PEG-VB12 NPs) were developed for microRNAs-532-3p mimics incorporating as targeting gene delivery systems (miR-532-3p@PLGA-PEG-VB12 NPs) to fight against transcobalamin II (CD320)-overexpressed GC cells' progression. The PLGA-PEG-VB12 NPs with appropriate particle sizes and good bio-compatibility could be selectively delivered into CD320-overexpressed GC cells, and significantly decrease the expression of apoptosis repressor with caspase recruitment domain (ARC). Following that, more pro-apoptotic protein (Bax) flowed from cytoplasm into mitochondria to form Bax oligomerization, thus induced mitochondrial damage, including mitochondrial membrane potentials (MMPs) loss and excessive production of mitochondrial reactive oxygen species (mitoROS). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by induced more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-depended cell apoptosis pathway. Therefore, our designed miR-532-3p@PLGA-PEG-VB12 NPs showed enhanced GC targeting ability, and could induce apoptosis through activating ARC/Bax/mitochondria-mediated apoptosis signaling pathway, finally remarkably suppressed proliferation of GC cells both in vitro and in vivo, which presented a promising treatment for GC.Zeolites have attractive features making them suitable carriers for drug delivery systems (DDS). As such, we loaded the anticancer drug 5-fluorouracil (5-FU), into two different zeolite structures, faujasite (NaY) and Linde Type L (LTL), to obtain different DDS. The prepared DDS were tested in vitro using breast cancer, colorectal carcinoma, and melanoma cell lines and in vivo using the chick embryo chorioallantoic membrane model (CAM). Both assays showed the best results for the Hs578T breast cancer cells, with a higher potentiation for 5-FU encapsulated in the zeolite LTL. To unveil the endocytic mechanisms involved in the internalization of the zeolite nanoparticles, endocytosis was inhibited pharmacologically in breast cancer and epithelial mammary human cells. The results suggest that a caveolin-mediated process was responsible for the internalized zeolite nanoparticles. Aiming to boost the DDS efficacy, the disc-shaped zeolite LTL outer surface was functionalized using amino (NH2) or carboxylic acid (COOH) groups and coated with poly-l-lysine (PLL). Positively functionalized surface LTL nanoparticles revealed to be non-toxic to human cells and, importantly, their internalization was faster and led to a higher tumor reduction in vivo. Overall, our results provide further insights into the mechanisms of interaction between zeolite-based DDS and cancer cells, and pave the way for future studies aiming to improve DDS anticancer activity.The development of biocompatible and transparent three-dimensional materials is desirable for corneal tissue engineering. Inspired from the cornea structure, gelatin methacryloyl-poly(2-hydroxymethyl methacrylate) (GelMA-p(HEMA)) composite hydrogel was fabricated. GelMA fibers were produced via electrospinning and covered with a thin layer of p(HEMA) in the presence of N,N'-methylenebisacrylamide (MBA) as cross-linker by drop-casting. The structure of resulting GelMA-p(HEMA) composite was characterized by spectrophotometry, microscopy, and swelling studies. Biocompatibility and biological properties of the both p(HEMA) and GelMA-p(HEMA) composite have been investigated by 3D cell culture, red blood cell hemolysis, and protein adsorption studies (i.e., human serum albumin, human immunoglobulin and egg white lysozyme). The optical transmittance of the GelMA-p(HEMA) composite was found to be approximately 70% at 550 nm. The GelMA-p(HEMA) composite was biocompatible with tear fluid proteins and convenient for cell adhesion and growth. Thus, as prepared hydrogel composite may find extensive applications in future for the development of corneal tissue engineering as well as preparation of stroma of the corneal material.This study introduces a mesoporous magnetic nano-system for the delivery of apigenin (API). A targeted therapeutic drug delivery system was prepared based on Fe2O3/Fe3O4@mSiO2-HA nanocomposites. Magnetic Fe2O3/Fe3O4 heterogeneous nanoparticles were first prepared via the rapid-combustion process. The effects of solvent type, solvent volume, calcination temperature, and calcination time on the crystal size and magnetism of the Fe2O3/Fe3O4 heterogeneous nanoparticles were investigated. The mesoporous silica shell was deposited on the Fe2O3/Fe3O4 heterogeneous nanoparticles using an improved Stöber method. HA was exploited as the targeting ligand. The specific surface area of the Fe2O3/Fe3O4@mSiO2 nanocomposites was 369.6 m2/g, which is 19 times higher than that of the magnetic Fe2O3/Fe3O4 heterogeneous nanoparticle cores. Drug release properties from the Fe2O3/Fe3O4@mSiO2-HA nanocomposites were studied, and the result showed that API-loaded nano-system had sustained release effect. Prussian blue staining and electrochemical performance variation showed that an external magnetic field facilitated cell uptake of Fe2O3/Fe3O4@mSiO2-HA nanocomposites. MTT assays showed that the cell inhibition effect of API-Fe2O3/Fe3O4@mSiO2-HA was stronger than that of free API at the same drug dose under a magnetic field and Fe2O3/Fe3O4@mSiO2-HA nanocomposites showed good biocompatibility. Fluorescence imaging, flow cytometry, western blot, reactive oxygen species (ROS), Superoxide dismutase (SOD) and malondialdehyde (MDA) kits verified that the enhanced therapeutic action was due to the promotion of apoptosis, lipid peroxidation, and ferroptosis. The magnetic nano-system (Fe2O3/Fe3O4@mSiO2-HA) showed good magnetic targeting and active hyaluronic acid targeting, and has the potential to provide a targeted delivery platform for many antitumor drugs.Having plasmonic absorption within the biological transparency window, titanium nitride (TiN) nanoparticles (NPs) can potentially outperform gold counterparts in phototheranostic applications, but characteristics of available TiN NPs are still far from required parameters. Recently emerged laser-ablative synthesis opens up opportunities to match these parameters as it makes possible the production of ultrapure low size-dispersed spherical TiN NPs, capable of generating a strong phototherapy effect under 750-800 nm excitation. This study presents the first assessment of toxicity, biodistribution and pharmacokinetics of laser-synthesized TiN NPs. Tests in vitro using 8 cell lines from different tissues evidenced safety of both as-synthesized and PEG-coated NPs (TiN-PEG NPs). After systemic administration in mice, they mainly accumulated in liver and spleen, but did not cause any sign of toxicity or organ damage up to concentration of 6 mg kg-1, which was confirmed by the invariability of blood biochemical parameters, weight and hemotoxicity examination. The NPs demonstrated efficient passive accumulation in EMT6/P mammary tumor, while concentration of TiN-PEG NPs was 2.2-fold higher due to "stealth" effect yielding 7-times longer circulation in blood. The obtained results evidence high safety of laser-synthesized TiN NPs for biological systems, which promises a major advancement of phototheranostic modalities on their basis.Human mesenchymal stem cells (hMSCs) are an attractive source for cell therapies because of their multiple beneficial properties, i.e. via immunomodulation and secretory factors. Microfluidics is particularly attractive for cell encapsulation since it provides a rapid and reproducible methodology for microgel generation of controlled size and simultaneous cell encapsulation. Here, we report the fabrication of hMSC-laden microcarriers based on in situ ionotropic gelation of water-soluble chitosan in a microfluidic device using a combination of an antioxidant glycerylphytate (G1Phy) compound and tripolyphosphate (TPP) as ionic crosslinkers (G1PhyTPP-microgels). These microgels showed homogeneous size distributions providing an average diameter of 104 ± 12 μm, somewhat lower than that of control (127 ± 16 μm, TPP-microgels). The presence of G1Phy in microgels maintained cell viability over time and upregulated paracrine factor secretion under adverse conditions compared to control TPP-microgels. Encapsulated hMSCs in G1PhyTPP-microgels were delivered to the subcutaneous space of immunocompromised mice via injection, and the delivery process was as simple as the injection of unencapsulated cells.