Optimizing the fabrication of electrospun nanofibers of prochlorperazine for enhanced dissolution and permeation properties.

Despite being an approved antiemetic for more than five decades, the clinical usefulness of prochlorperazine is limited by its low solubility and inconsistent absorption in the gastrointestinal tract, which presents challenges for nanotherapeutic interventions. Here, we report the preparation of a highly soluble and permeable nanofiber formulation of prochlorperazine using the Quality-by-Design approach. The final nanofiber formulation with drug entrapment of 88.02 ± 1.14 % was obtained at 20.0 kV, with a flow rate of 0.5 ml/h and tip-to-collector distance of 19.9 cm. Physio-mechanical properties, such as thickness (0.42 ± 0.02 mm), pH resistance (7.04 ± 0.08), folding endurance (54 ± 5), and tensile strength (0.244 ± 0.02 N.mm-2), were appropriate for packaging and application to oromucosal surfaces. The content uniformity (93.48-106.63 %) and weight variation (<1.8 mg) of the optimal nanofiber formulation were within the permissible limits prescribed for orodispersible films. Microscopical investigations confirm a randomly deposited and dense network of woven nanofibers with an average diameter of 363 ± 5.66 nm. The drug particles were embedded homogeneously on the fiber in the nanoform (4.27 ± 1.34 nm). The spectral analysis using TEM-EDS shows diffraction peaks of sulfur and chlorine, the elemental constituents of prochlorperazine. The drug was amorphized in the nanofiber formulation, as led by the decline of the crystallinity index from 87.25 % to 7.93 % due to electrostatic destabilization and flash evaporation of the solvent. The enthalpy of fusion values of the drug in the nanofiber mat decreased significantly to 23.6 J/g compared to its pristine form, which exhibits a value of 260.7 J/g. The nanofibers were biocompatible with oral mucosal cells, and there were no signs of mucosal irritation compared to 1 % sodium lauryl sulfate. The fiber mats rapidly disintegrated within <1 s and released ≈91.49 ± 2.1 % of the drug within 2 min, almost 2-fold compared to the commercial Stemetil MD® tablets. Similarly, the cumulative amount of the drug permeated across the unit area of the oromucosal membrane was remarkably high (31.28 ± 1.30 µg) compared to 10.17 ± 1.11 µg and 13.10 ± 1.79 µg from the cast film and drug suspension. Our results revealed these nanofiber formulations have the potential to be fast-dissolving oromucosal delivery systems, which can result in enhanced bioavailability with an early onset of action due to rapid disintegration, dissolution, and permeation.

Evaluating models and assessment techniques for understanding oral biofilm complexity.

Oral biofilms are three-dimensional (3D) complex entities initiating dental diseases and have been evaluated extensively in the scientific literature using several biofilm models and assessment techniques. The list of biofilm models and assessment techniques may overwhelm a novice biofilm researcher. This narrative review aims to summarize the existing literature on biofilm models and assessment techniques, providing additional information on selecting an appropriate model and corresponding assessment techniques, which may be useful as a guide to the beginner biofilm investigator and as a refresher to experienced researchers. The review addresses previously established 2D models, outlining their advantages and limitations based on the growth environment, availability of nutrients, and the number of bacterial species, while also exploring novel 3D biofilm models. The growth of biofilms on clinically relevant 3D models, particularly melt electrowritten fibrous scaffolds, is discussed with a specific focus that has not been previously reported. Relevant studies on validated oral microcosm models that have recently gaining prominence are summarized. The review analyses the advantages and limitations of biofilm assessment methods, including colony forming unit culture, crystal violet, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt assays, confocal microscopy, fluorescence in situ hybridization, scanning electron microscopy, quantitative polymerase chain reaction, and next-generation sequencing. The use of more complex models with advanced assessment methodologies, subject to the availability of equipment/facilities, may help in developing clinically relevant biofilms and answering appropriate research questions.

Effects of periodontal cells-derived extracellular vesicles on mesenchymal stromal cell function.

OBJECTIVE: To enrich and compare three extracellular vesicles-EV subtypes (apoptotic bodies, microvesicles and small EV) from three periodontal cells (periodontal ligament cells-PDLCs, alveolar bone-derived osteoblasts-OBs and gingival fibroblasts-GFs), and assess uptake and cell function changes in buccal fat pad-derived mesenchymal stromal cells (BFP-MSCs). BACKGROUND: Periodontal cells such as PDLCs, OBs and GFs have the potential to enhance bone and periodontal regeneration, but face significant challenges, such as the regulatory and cost implications of in vitro cell culture and storage. To address these challenges, it is important to explore alternative 'cell-free' strategies, such as extracellular vesicles which have emerged as promising tools in regenerative medicine, to facilitate osteogenic differentiation and bone regeneration. METHODS AND MATERIALS: Serial centrifuges at 2600 and 16 000 g were used to isolate apoptotic bodies and microvesicles respectively. Small EV-sEV was enriched by our in-house size exclusion chromatography (SEC). The cellular uptake, proliferation, migration and osteogenic/adipogenic differentiation genes were analysed after EVs uptake in BFP-MSCs. RESULTS: Three EV subtypes were enriched and characterised by morphology, particle size and EV-associated protein expression-CD9. Cellular uptake of the three EVs subtypes was observed in BFP-MSCs for up to 7 days. sEV from the three periodontal cells promoted proliferation, migration and osteogenic gene expression. hOBs-sEV showed superior levels of osteogenesis markers compared to that hPDLCs-sEV and hGFs-sEV, while hOBs-16k EV promoted adipogenic gene expression compared to that from hPDLCs and hGFs. CONCLUSIONS: Our proof-of-concept data demonstrate that hOBs-sEV might be an alternative cell-free therapeutic for bone tissue engineering.

Nanosurface Texturing for Enhancing the Antibacterial Effect of Biodegradable Metal Zinc: Surface Modifications.

Zinc (Zn) as a biodegradable metal has attracted research interest for bone reconstruction, with the aim of eliminating the need for a second removal surgery and minimizing the implant-to-bone transfer of stress-shielding to maintain bone regeneration. In addition, Zn has been shown to have antibacterial properties, particularly against Gram-negative bacteria, and is often used as a surface coating to inhibit bacterial growth and biofilm formation. However, the antibacterial property of Zn is still suboptimal in part due to low Zn ion release during degradation that has to be further improved in order to meet clinical requirements. This work aims to perform an innovative one-step surface modification using a nitric acid treatment to accelerate Zn ion release by increasing surface roughness, thereby endowing an effective antimicrobial property and biofilm formation inhibition. The antibacterial performance against Staphylococci aureus was evaluated by assessing biofilm formation and adhesion using quantitative assays. The surface roughness of acid-treated Zn (Ra ~ 30 nm) was significantly higher than polished Zn (Ra ~ 3 nm) and corresponded with the marked inhibition of bacterial biofilm, and this is likely due to the increased surface contact area and Zn ion accumulation. Overall, surface modification due to nitric acid etching appears to be an effective technique that can produce unique morphological surface structures and enhance the antibacterial properties of biodegradable Zn-based materials, thus increasing the translation potential toward multiple biomedical applications.

A Review of 3D Polymeric Scaffolds for Bone Tissue Engineering: Principles, Fabrication Techniques, Immunomodulatory Roles, and Challenges.

Over the last few years, biopolymers have attracted great interest in tissue engineering and regenerative medicine due to the great diversity of their chemical, mechanical, and physical properties for the fabrication of 3D scaffolds. This review is devoted to recent advances in synthetic and natural polymeric 3D scaffolds for bone tissue engineering (BTE) and regenerative therapies. The review comprehensively discusses the implications of biological macromolecules, structure, and composition of polymeric scaffolds used in BTE. Various approaches to fabricating 3D BTE scaffolds are discussed, including solvent casting and particle leaching, freeze-drying, thermally induced phase separation, gas foaming, electrospinning, and sol-gel techniques. Rapid prototyping technologies such as stereolithography, fused deposition modeling, selective laser sintering, and 3D bioprinting are also covered. The immunomodulatory roles of polymeric scaffolds utilized for BTE applications are discussed. In addition, the features and challenges of 3D polymer scaffolds fabricated using advanced additive manufacturing technologies (rapid prototyping) are addressed and compared to conventional subtractive manufacturing techniques. Finally, the challenges of applying scaffold-based BTE treatments in practice are discussed in-depth.

Polyurethane and cellulose acetate micro-nanofibers containing rosemary essential oil, and decorated with silver nanoparticles for wound healing application.

In this study, polyurethane (PU) and cellulose acetate (CA) electrospun fibers encapsulating rosemary essential oil (REO) and adsorbed silver (Ag) nanoparticles (NPs) were fabricated. The biologically inspired materials were analyzed for physicochemical characteristics using scanning electron microscopy, X-ray diffractometer, Fourier transform infrared, thermal gravimetric analysis, X-ray photoelectron spectroscopy, water contact angle, and water uptake studies. Results confirmed the presence of CA and Ag NPs on the PU micro-nanofibers increased the hydrophilicity from 107.1 ± 0.36o to 26.35 ± 1.06o. The water absorption potential increased from 0.07 ± 0.04 for pristine PU fibers to 12.43 ± 0.49 % for fibers with 7 wt% of CA, REO, and Ag NPs. The diffractometer confirmed the 2θ of 38.01°, 44.13o, and 64.33o, corresponding to the diffraction planes of Ag on the fibers. The X-ray photoelectron spectroscopy confirmed microfibers interfacial chemical interaction and surface changes due to CA, REO, and Ag presence. The inhibition tests on Staphylococcus aureus and Escherichia coli indicated that composites are antibacterial in activity. Moreover, synergistic interactions of REO and Ag NPs resulted in superior antibacterial activity. The cell viability and attachment assay showed improved hydrophilicity of the fibers, which resulted in better attachment of cells to the micro-nanofibers, similar to the natural extracellular matrix in the human body.

Fabrication and characterization of a 3D polymicrobial microcosm biofilm model using melt electrowritten scaffolds.

The majority of current biofilm models or substrates are two-dimensional (2D) and support biofilm growth in the horizontal plane only. Three-dimensional (3D) substrates may support both horizontal and vertical biofilm growth. This study compared biofilm growth quantity and quality between highly porous 3D micrometric fibrous scaffolds and 2D film substrates fabricated from medical grade polycaprolactone (mPCL). Melt electrowriting (MEW), a high-resolution additive manufacturing technology, was employed to design orderly aligned fine (~12 µm) fibre-based 3D scaffolds, while 2D films were fabricated by a casting method. The 3D scaffolds with a controlled pore size of 100 and 250 µm and thickness of ~0.8 mm and 2D films were incubated in pooled saliva collected from six volunteers for 1, 2, 4, 7 and 10 days at 37 °C to facilitate polymicrobial biofilm formation. Crystal violet assay demonstrated greater biofilm biomass in 3D MEW scaffolds than in 2D films. Biofilm thickness in 3D scaffolds was significantly higher compared to the biofilm thickness in 2D films. Both biovolume and substratum coverage of the biofilms was higher in the 3D scaffolds compared to 2D films. Polymeric bridges, pores, and channels characteristic of biofilms could be demonstrated by scanning electron microscopy. 16S rRNA sequencing demonstrated that the polymicrobial biofilms in the 3D scaffolds were able to retain 60-70 % of the original inoculum microbiome after 4 days. The MEW-fabricated 3D fibrous scaffold is a promising substrate for supporting multidirectional biofilm growth and modelling of a polymicrobial microcosm.

Development of New Bio-Composite of PEO/Silk Fibroin Blends Loaded with Piezoelectric Material.

New bio-composite nanofibers composed of polyethylene oxide (PEO)/silk fibroin (SF)/barium titanate (BaTiO3) are introduced in this study. The SF solution was added to the PEO solution to form a PEO/SF blend with different weight percentages (5, 10, 15, 20 wt.%). The PEO/15 wt.% SF blend was selected to continue the experimental plan based on the optimum nanofiber morphology. Different wt.% of BaTiO3 particles (0.2, 0.4, 0.8, 1 wt.%) were added to the PEO/15 wt.% SF blend solution, and the suspensions obtained were introduced to an electrospinning device. The fabricated tissue was characterized by scanning electron microscope (SEM), X-ray diffraction (XRD) and Fourier-transform infrared (FTIR) spectroscopy. The zeta potential of the solution and the piezoelectric performance of the fabricated tissue were characterized. A newly designed pizoTester was used to investigate piezoelectric properties. The results showed that a well-organized, smooth PEO/15 wt.% SF/0.2 wt.% BaTiO3 nanofiber composite with low bead contents was obtained. Improved properties and electrical coupling were achieved in the newly introduced material. Electrospun PEO/15 wt.% SF/0.2 wt.% BaTiO3 mats increased the output voltage (1150 mV) compared to pristine PEO and PEO/SF composite fibers (410 and 290 mV, respectively) upon applying 20 N force at 5 Hz frequency. The observed enhancement in piezoelectric properties suggests that the prepared composite could be a promising material in cardiac tissue engineering (CTE).

Surface Modification of Pure Zinc by Acid Etching: Accelerating the Corrosion Rate and Enhancing Biocompatibility and Antibacterial Characteristics.

Zinc (Zn) has recently been identified as an auspicious biodegradable metal for medical implants and devices due to its tunable mechanical properties and good biocompatibility. However, the slow corrosion rate of Zn in a physiological environment does not meet the requirements for biodegradable implants, hindering its clinical translation. The present study aimed to accelerate the corrosion rate of pure Zn by utilizing acid etching to roughen the surface and increase the substrate surface area. The effects of acid etching on surface morphology, surface roughness, tensile properties, hardness, electrochemical corrosion and degradation behavior, cytocompatibility, direct cell attachment, and biofilm formation were investigated. Interestingly, acid-treated Zn showed an exceptionally high rate of corrosion (∼226-125 µm/year) compared to untreated Zn (∼62 µm/year), attributed to the increased surface roughness (Ra ∼ 1.12 µm) of acid-etched samples. Immersion tests in Hank's solution revealed that acid etching accelerated the degradation rate of Zn samples. In vitro, MC3T3-E1 cell lines in 50 and 25% conditioned media extracts of treated samples showed good cytocompatibility. Reduced bacterial adhesion, biofilm formation, and dispersion were observed for Staphylococci aureus biofilms cultured on acid-etched pure Zn substrates. These results suggest that the surface modification of biodegradable pure Zn metals by acid etching markedly increases the translation potential of zinc for various biomedical applications.

Novel Nano-Engineered Biomaterials for Bone Tissue Engineering.

This Special Issue of Nanomaterials explores the recent advances relating to nano-engineered strategies for biomaterials and implants in bone tissue engineering [...].

Influence of Bioinspired Lithium-Doped Titanium Implants on Gingival Fibroblast Bioactivity and Biofilm Adhesion.

Soft tissue integration (STI) at the transmucosal level around dental implants is crucial for the long-term success of dental implants. Surface modification of titanium dental implants could be an effective way to enhance peri-implant STI. The present study aimed to investigate the effect of bioinspired lithium (Li)-doped Ti surface on the behaviour of human gingival fibroblasts (HGFs) and oral biofilm in vitro. HGFs were cultured on various Ti surfaces-Li-doped Ti (Li_Ti), NaOH_Ti and micro-rough Ti (Control_Ti)-and were evaluated for viability, adhesion, extracellular matrix protein expression and cytokine secretion. Furthermore, single species bacteria (Staphylococcus aureus) and multi-species oral biofilms from saliva were cultured on each surface and assessed for viability and metabolic activity. The results show that both Li_Ti and NaOH_Ti significantly increased the proliferation of HGFs compared to the control. Fibroblast growth factor-2 (FGF-2) mRNA levels were significantly increased on Li_Ti and NaOH_Ti at day 7. Moreover, Li_Ti upregulated COL-I and fibronectin gene expression compared to the NaOH_Ti. A significant decrease in bacterial metabolic activity was detected for both the Li_Ti and NaOH_Ti surfaces. Together, these results suggest that bioinspired Li-doped Ti promotes HGF bioactivity while suppressing bacterial adhesion and growth. This is of clinical importance regarding STI improvement during the maintenance phase of the dental implant treatment.

The Mechanosensing and Global DNA Methylation of Human Osteoblasts on MEW Fibers.

Cells interact with 3D fibrous platform topography via a nano-scaled focal adhesion complex, and more research is required on how osteoblasts sense and respond to random and aligned fibers through nano-sized focal adhesions and their downstream events. The present study assessed human primary osteoblast cells' sensing and response to random and aligned medical-grade polycaprolactone (PCL) fibrous 3D scaffolds fabricated via the melt electrowriting (MEW) technique. Cells cultured on a tissue culture plate (TCP) were used as 2D controls. Compared to 2D TCP, 3D MEW fibrous substrates led to immature vinculin focal adhesion formation and significantly reduced nuclear localization of the mechanosensor-yes-associated protein (YAP). Notably, aligned MEW fibers induced elongated cell and nucleus shape and highly activated global DNA methylation of 5-methylcytosine, 5-hydroxymethylcytosine, and N-6 methylated deoxyadenosine compared to the random fibers. Furthermore, although osteogenic markers (osterix-OSX and bone sialoprotein-BSP) were significantly enhanced in PCL-R and PCL-A groups at seven days post-osteogenic differentiation, calcium deposits on all seeded samples did not show a difference after normalizing for DNA content after three weeks of osteogenic induction. Overall, our study linked 3D extracellular fiber alignment to nano-focal adhesion complex, nuclear mechanosensing, DNA epigenetics at an early point (24 h), and longer-term changes in osteoblast osteogenic differentiation.

Alkali-Treated Titanium Coated with a Polyurethane, Magnesium and Hydroxyapatite Composite for Bone Tissue Engineering.

The aim of this study was to form a functional layer on the surface of titanium (Ti) implants to enhance their bioactivity. Layers of polyurethane (PU), containing hydroxyapatite (HAp) nanoparticles (NPs) and magnesium (Mg) particles, were deposited on alkali-treated Ti surfaces using a cost-effective dip-coating approach. The coatings were assessed in terms of morphology, chemical composition, adhesion strength, interfacial bonding, and thermal properties. Additionally, cell response to the variably coated Ti substrates was investigated using MC3T3-E1 osteoblast-like cells, including assessment of cell adhesion, cell proliferation, and osteogenic activity through an alkaline phosphatase (ALP) assay. The results showed that the incorporation of HAp NPs enhanced the interfacial bonding between the coating and the alkali-treated Ti surface. Furthermore, the presence of Mg and HAp particles enhanced the surface charge properties as well as cell attachment, proliferation, and differentiation. Our results suggest that the deposition of a bioactive composite layer containing Mg and HAp particles on Ti implants may have the potential to induce bone formation.

Biosynthesis of Bonelike Apatite 2D Nanoplate Structures Using Fenugreek Seed Extract.

An innovative, biomimetic, green synthesis approach was exploited for the synthesis of humane and environmental friendly nanomaterials for biomedical applications. Ultrafine bonelike apatite (BAp) 2D plate-like structures were prepared using fenugreek seed extract during the biosynthesis wet-chemical precipitation route. The chemical analysis, morphology and structure of the prepared 2D nanoplates were characterized by inductively coupled plasma atomic emission spectroscopy (ICP-OES), electron microscopy (SEM and TEM), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. A 2D plate-like nanostructure of BAp with an average width (length) of 12.67 ± 2 nm and thickness of 3.8 ± 1.2 nm was obtained. BAp 2D crystals were tuned by interaction with the fenugreek organic molecules during the fabrication process. In addition to Ca and P ions, bone mineral sources such as K, Mg, Na, SO4 and CO3 ions were incorporated into BAp nanoplates using fenugreek seed extract. The overall organic molecule concentration in the reaction process increased the effectiveness of hydroxyl groups as nucleation sites for BAp crystals. Accordingly, the size of the biosynthesized BAp plate-like structure was reduced to its lowest value. Biosynthesis BAp 2D plate-like nanocrystals showed good viability and higher growth of MC3T3 osteoblast-like structures than that of the control sample. BAp 2D nanoplates prepared by a facile, ecofriendly and cost-effective approach could be considered a favorable osteoconductive inorganic biomaterial for bone regeneration applications.

Electrospun nanofibers for the delivery of active drugs through nasal, oral and vaginal mucosa: Current status and future perspectives.

Transmucosal surfaces bypass many limitations associated with conventional drug delivery (oral and parenteral routes), such as poor absorption rate, enzymatic activity, acidic environment and first-pass metabolism occurring inside the liver. However, these surfaces have several disadvantages such as poor retention time, narrow absorption window and continuous washout of the drug by the surrounding fluids. Electrospun nanofibers with their unique surface properties and encapsulation efficiency may act as novel drug carriers to overcome the challenges associated with conventional drug delivery routes, so as to achieve desired therapeutic responses. This review article provides detailed information regarding the challenges faced in the mucosal delivery of drugs, and the use of nanofiber systems as an alternative to deliver drugs to the systemic circulation, as well as local drug administration. The physiological and anatomical features of different types of mucosal surfaces and current challenges are systematically discussed. We also address future considerations in the area of transmucosal delivery of some important drugs.

Fabrication of multifunctional cellulose/TiO2 /Ag composite nanofibers scaffold with antibacterial and bioactivity properties for future tissue engineering applications.

In the present work, a novel strategy was explored to fabricate nanofiber scaffolds consisting of cellulose assimilated with titanium dioxide (TiO2 ) and silver (Ag) nanoparticles (NPs). The concentration of the TiO2 NPs in the composite was adjusted to 1.0, 1.5, and 2.0 wt % with respect to polymer concentration used for the electrospinning of colloidal solutions. The fabricated composite scaffolds were dispensed to alkaline deacetylation using 0.05 M NaOH to remove the acetyl groups in order to generate pure cellulose nanofibers containing TiO2 NPs. Moreover, to augment our nanofiber scaffolds with antibacterial activity, the in situ deposition approach of using Ag NPs was utilized with varied molar concentrations of 0.14, 0.42, and 0.71 M. The physicochemical properties of the nanofibers were identified by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) and contact angle meter studies. This demonstrated the presence of both TiO2 and Ag NPs and complete deacetylation of nanofibers. The antibacterial efficiency of the nanofibers was scrutinized against Escherichia coli and Staphylococcus aureus, revealing proper in situ deposition of Ag NPs and confirming the nanofibers are antibacterial in nature. The biocompatibility of the scaffolds was accustomed using chicken embryo fibroblasts, which confirmed their potential role to be used as wound-healing materials. Furthermore, the fabricated scaffolds were subjected to analysis in simulated body fluid at 37°C to induce mineralization for future osseous tissue integration. These results indicate that fabricated composite nanofiber scaffolds with multifunctional characteristics will have a highest potential as a future candidate for promoting new tissues artificially.

Polyhydroxyalkanoate (PHA): applications in drug delivery and tissue engineering.

INTRODUCTION: The applications of naturally obtained polymers are tremendously increased due to them being biocompatible, biodegradable, environmentally friendly and renewable in nature. Among them, polyhydroxyalkanoates are widely studied and they can be utilized in many areas of human life research such as drug delivery, tissue engineering, and other medical applications. AREAS COVERED: This review provides an overview of the polyhydroxyalkanoates biosynthesis and their possible applications in drug delivery in the range of micro- and nano-size. Moreover, the possible applications in tissue engineering are covered considering macro- and microporous scaffolds and extracellular matrix analogs. EXPERT COMMENTARY: The majority of synthetic plastics are non-biodegradable so, in the last years, a renewed interest is growing to develop alternative processes to produce biologically derived polymers. Among them, PHAs present good properties such as high immunotolerance, low toxicity, biodegradability, so, they are promisingly using as biomaterials in biomedical applications.

Effects of Gradient and Offset Architectures on the Mechanical and Biological Properties of 3-D Melt Electrowritten (MEW) Scaffolds.

This study describes the fabrication and characterization of three-dimensional (3-D) poly(ε-caprolactone) (PCL) scaffolds with defined pore architectures prepared using the melt electrowriting (MEW) technique. Three homogeneous pore-sized (250, 500, and 750 µm) scaffolds, two fiber offset (30/70% and 50/50%), and a three-layered (250 µm bottom-500 µm middle-750 µm top) gradient pore-sized scaffolds were designed and printed with ∼10 µm fibers. The mechanical properties (tensile and compression tests), total surface area, porosity of these scaffolds, and their ability to promote the attachment and proliferation of human osteoblasts were then compared. All scaffolds induced good tensile properties; however, they reacted differently during compressive testing. The offset 30/70 scaffold had the highest surface area to volume ratio which enhanced osteoblast attachment after 3 days of cell culture. While the highest initial level of osteoblast attachment at day 1 was found on the 250 µm homogeneous scaffold, the highest degree of cell proliferation and infiltration at day 30 was observed in the three-layered graded porosity scaffold. In terms of physical and biological properties to support bone cell distribution and migration through the entire structure of the scaffold, our results suggest that melt electrowritten offset and gradient scaffolds are good candidate platforms for cell infiltration and growth compared to homogeneous scaffolds.

A Multifunctional Zinc Oxide/Poly(Lactic Acid) Nanocomposite Layer Coated on Magnesium Alloys for Controlled Degradation and Antibacterial Function.

In the present work, magnesium (Mg) AZ31 alloy was coated with a multifunctional membrane layer composed of ZnO nanoparticles (NPs) embedded in a poly(lactic acid) (PLA) matrix. We aimed to produce a stable coating that would be used to control the degradation rate of the Mg alloy and promote a local antibacterial activity. ZnO NPs were dispersed at 5 and 10 wt % in a PLA solution and dip-coated onto the AZ31 substrate. Surface topography, chemical composition, thickness, electrochemical corrosion performance, mass variation, antibacterial activity, adhesion performance, and cytotoxicity of an uncoated control and coated alloys were investigated. The results indicated that the incorporation of ZnO NPs at various concentrations affords a dramatic control over surface topography and degradation rates under in vitro and in vivo environmental conditions when compared to the uncoated Mg alloy control. In addition, the results confirmed that the coated layer exerts antibacterial properties and supports cell growth, indicating this system may have utility for bone tissue engineering applications.

Electrospun biphasic tubular scaffold with enhanced mechanical properties for vascular tissue engineering.

Polymer scaffolds produced through an electrospinning process are frequently explored as tissue substitutes for regenerative medicine. Despite offering desirable surface area to volume ratios and tailorable pore sizes, their poor structural mechanical properties limit their applicability in load-bearing regions. In this study, we present a simple strategy to improve the mechanical properties of a vascular graft scaffold. We achieved the formation of biphasic tubular scaffolds by electrospinning polyurethane (PU) onto an airbrushed tube made of polycaprolactone (PCL). After preparation, the scaffold was subsequently thermally-crosslinked (60°C) to strengthen the bonding between the two materials. The tensile strength and tensile elastic (Young's) modulus of the biphasic scaffolds were significantly enhanced from 4.5±1.72 and 45±15MPa (PU-only) up to 67.5±2.4 and 1039±81.8MPa (PCL/PU; p<0.05). Additionally, suture retention force, burst pressure, and compliance were all improved. The cytotoxicity of the fabricated samples was investigated using an MTT assay after 7days of cell culture and found to be negligible (~100% viability). In conclusion, we have demonstrated the preparation and characterization of a stable and mechanically robust vascular graft scaffold using a novel combination of well-established fabrication techniques. This study could also be extended to the fabrication of other biphasic scaffolds to better enhance the mechanical properties of the electrospun fibers mat without deteriorating its architecture structure.