An Adhesive Bioink toward Biofabrication under Wet Conditions.

Three-dimensional (3D) bioprinting is driving significant innovations in biomedicine over recent years. Under certain scenarios such as in intraoperative bioprinting, the bioinks used should exhibit not only cyto/biocompatibility but also adhesiveness in wet conditions. Herein, an adhesive bioink composed of gelatin methacryloyl, gelatin, methacrylated hyaluronic acid, and skin secretion of Andrias davidianus is designed. The bioink exhibits favorable cohesion to allow faithful extrusion bioprinting in wet conditions, while simultaneously showing good adhesion to a variety of surfaces of different chemical properties, possibly achieved through the diverse bonds presented in the bioink formulation. As such, this bioink is able to fabricate sophisticated planar and volumetric constructs using extrusion bioprinting, where the dexterity is further enhanced using ergonomic handheld bioprinters to realize in situ bioprinting. In vitro experiments reveal that cells maintain high viability; further in vivo studies demonstrate good integration and immediate injury sealing. The characteristics of the bioink indicate its potential widespread utility in extrusion bioprinting and will likely broaden the applications of bioprinting toward situations such as in situ dressing and minimally invasive tissue regeneration.

A Natural Hydrogel with Prohealing Properties Enhances Tendon Regeneration.

Tendon regeneration and reduction of peritendinous adhesion remain major clinical challenges. This study addresses these challenges by adopting a unique hydrogel derived from the skin secretion of Andrias davidianus (SSAD) and taking advantage of its biological effects, adhesiveness, and controllable microstructures. The SSAD-derived hydrogel contains many cytokines, which could promote tendon healing. In vitro, leach liquid of SSAD powder could promote tendon stem/progenitor cells migration. In vivo, the SSAD-derived hydrogel featuring double layers possesses strong adhesiveness and could reconnect ruptured Achilles tendons of Sprague-Dawley rats without suturing. The intimal SSAD-derived hydrogel, with a pore size of 241.7 ± 21.0 µm, forms the first layer of the hydrogel to promote tendon healing, and the outer layer SSAD-derived hydrogel, with a pore size of 3.3 ± 1.4 µm, reducing peritendinous adhesion by serving as a dense barrier. Additionally, the SSAD-derived hydrogel exhibits antioxidant and antibacterial characteristics, which further contribute to the reduction of peritendinous adhesion. In vivo studies suggest that the SSAD-derived hydrogel reduces peritendinous adhesion, increases collagen fiber deposition, promotes cell proliferation, and improves the biomechanical properties of the regenerated tendons, indicating better functional restoration. The SSAD-derived bilayer hydrogel may be a feasible biomaterial for tendon repair in the future.

A Bioinspired Hemostatic Powder Derived from the Skin Secretion of Andrias davidianus for Rapid Hemostasis and Intraoral Wound Healing.

High-performance hemostasis has become increasingly essential in treating various traumas. However, available topical hemostats still have various drawbacks and side-effects. Herein, hemostatic powders derived from the skin secretion of Andrias davidianus (SSAD) with controllable particle size are prepared using feasible frozen-ball milling following lyophilization for hemorrhage-control. Scanning electron microscopy, rheometry, and Brunauer-Emmett-Teller test are used to characterize the coagulation-promoting surface topography, rheological properties, and porous structure of the SSAD particles. The blood-coagulation assays showed that the SSAD powders can induce blood-absorption in a particle size-dependent manner. Particle sizes of the SSAD powders larger than 200 µm and smaller than 800 µm greatly affect the blood-clotting rate. Associated with the thromboelastography (TEG) and amino acid/protein composition analyses, the accessibility and diffusion of blood are mainly dependent on the wettability, adhesivity, and clotting factors of the SSAD particles. Rapid hemostasis in vivo further involves three hemorrhage models (liver, femoral artery, and tail) as well as an oral wound model, which suggest favorable hemostatic and simultaneous regenerative effects of the SSAD hemostatic powder. Considering its degradability and good biocompatibility, SSAD can be an optimal candidate for a new class of inexpensive, natural, and promising hemostatic and wound-dressing agent.

A Clinical Investigation of the Efficacy of a Dual Zinc plus Arginine Dentifrice for Controlling Oral Malodor.

OBJECTIVES: The objective of this independent, double-blind clinical study was to assess the efficacy of a new Dual Zinc plus Arginine dentifrice (Colgate-Palmolive Co., New York, NY, USA) containing zinc (zinc oxide, zinc citrate) 0.96%, 1.5% arginine, and 1450 ppm F as sodium fluoride in a silica base for the 12-hour overnight oral malodor reduction after three weeks of product use, relative to that of a regular fluoride dentifrice containing 1450 ppm F as sodium fluoride in a silica base (Colgate-Palmolive Co., New York, NY, USA). METHODS: A total of eighty (80) adult male and female subjects from Chengdu, People's Republic of China, were enrolled in this clinical study. Following an assessment of the oral soft and hard tissues, subjects were evaluated for baseline oral malodor by a panel of four trained and calibrated judges using a nine-point organoleptic hedonic scale. They were then randomly assigned to one of two treatment groups (Dual Zinc plus Arginine - test; regular fluoride dentifrice - control). Subjects were provided with their assigned dentifrice and toothbrush and instructed to brush their teeth twice daily (morning and evening) for one minute. After three weeks, subjects returned to the study site for their follow-up evaluation of malodor after having refrained from brushing for 12 hours (overnight). RESULTS: Eighty (80) subjects completed the study. After three weeks of product use, subjects in the Dual Zinc plus Arginine dentifrice group and the regular fluoride dentifrice group showed statistically significant (p < 0.001) reductions of 38.9% and 11.6%, respectively, in organoleptic scores as compared to baseline. Relative to the regular fluoride dentifrice group, subjects in the Dual Zinc plus Arginine dentifrice group exhibited a statistically significant (p< 0.001) reduction of 30.8% in oral malodor. The quality of breath for subjects in the Dual Zinc plus Arginine dentifrice group was in the range corresponding to pleasant breath, whereas the quality of breath for subjects in the regular fluoride dentifrice group was in the range corresponding to unpleasant breath. CONCLUSIONS: The overall results of this double-blind clinical study support the conclusion that a new Dual Zinc plus Arginine dentifrice containing zinc (zinc oxide, zinc citrate) 0.96%, 1.5% arginine, and 1450 ppm fluoride as sodium fluoride in a silica base provides a significantly greater reduction in oral malodor as compared to a regular fluoride dentifrice containing 1450 ppm fluoride as sodium fluoride in a silica base 12 hours post-brushing (overnight) after 3 weeks of product use.

Cyclophilin B facilitates the replication of Orf virus.

BACKGROUND: Viruses interact with host cellular factors to construct a more favourable environment for their efficient replication. Expression of cyclophilin B (CypB), a cellular peptidyl-prolyl cis-trans isomerase (PPIase), was found to be significantly up-regulated. Recently, a number of studies have shown that CypB is important in the replication of several viruses, including Japanese encephalitis virus (JEV), hepatitis C virus (HCV) and human papillomavirus type 16 (HPV 16). However, the function of cellular CypB in ORFV replication has not yet been explored. METHODS: Suppression subtractive hybridization (SSH) technique was applied to identify genes differentially expressed in the ORFV-infected MDBK cells at an early phase of infection. Cellular CypB was confirmed to be significantly up-regulated by quantitative reverse transcription-PCR (qRT-PCR) analysis and Western blotting. The role of CypB in ORFV infection was further determined using Cyclosporin A (CsA) and RNA interference (RNAi). Effect of CypB gene silencing on ORFV replication by 50% tissue culture infectious dose (TCID50) assay and qRT-PCR detection. RESULTS: In the present study, CypB was found to be significantly up-regulated in the ORFV-infected MDBK cells at an early phase of infection. Cyclosporin A (CsA) exhibited suppressive effects on ORFV replication through the inhibition of CypB. Silencing of CypB gene inhibited the replication of ORFV in MDBK cells. In conclusion, these data suggest that CypB is critical for the efficient replication of the ORFV genome. CONCLUSIONS: Cellular CypB was confirmed to be significantly up-regulated in the ORFV-infected MDBK cells at an early phase of infection, which could effectively facilitate the replication of ORFV.

Evaluation of Fluorescence Imaging with Reflectance Enhancement (FIRE) for Quantifying Enamel Demineralization In vitro.

OBJECTIVES: To assess the ability of fluorescence imaging with reflectance enhancement (FIRE) to quantify early enamel demineralization in vitro. METHODS: A total of 30 bovine enamel specimens were immersed in demineralizing solution to produce artificial caries. Specimens were examined by FIRE, quantitative light-induced fluorescence (QLF), and polarized light microscopy (PLM) at baseline and after 0.5, 1, 2, 4, 8, 24, 48 and 72 h of immersion. Fluorescence loss measured by FIRE and QLF was compared with lesion depth measurements by PLM. RESULTS: Over all time points, measurement of fluorescence loss by FIRE correlated well with the measurement of x0394;F by QLF and of x0394;Q by QLF. Both FIRE and QLF techniques showed significant correlation with PLM. CONCLUSION: FIRE technology may be useful for quantifying enamel demineralization in vitro.

Uniaxially aligned electrospun all-cellulose nanocomposite nanofibers reinforced with cellulose nanocrystals: scaffold for tissue engineering.

Uniaxially aligned cellulose nanofibers with well oriented cellulose nanocrystals (CNCs) embedded were fabricated via electrospinning using a rotating drum as the collector. Scanning electron microscope (SEM) images indicated that most cellulose nanofibers were uniaxially aligned. The incorporation of CNCs into the spinning dope resulted in more uniform morphology of the electrospun cellulose/CNCs nanocomposite nanofibers (ECCNN). Polarized light microscope (PLM) and transmission electron microscope (TEM) showed that CNCs dispersed well in ECCNN nonwovens and achieved considerable orientation along the long axis direction. This unique hierarchical microstructure of ECCNN nonwovens gave rise to remarkable enhancement of their physical properties. By incorporating 20% loading (in weight) of CNCs, the tensile strength and elastic modulus of ECCNN along the fiber alignment direction were increased by 101.7 and 171.6%, respectively. Their thermal stability was significantly improved as well. In addition, the ECCNN nonwovens were assessed as potential scaffold materials for tissue engineering. It was elucidated from MTT tests that the ECCNN were essentially nontoxic to human cells. Cell culture experiments demonstrated that cells could proliferate rapidly not only on the surface but also deep inside the ECCNN. More importantly, the aligned nanofibers of ECCNN exhibited a strong effect on directing cellular organization. This feature made the scaffold particularly useful for various artificial tissues or organs, such as blood vessel, tendon, nerve, and so on, in which cell orientation was crucial for their performance.

Remineralization of early caries by chewing sugar-free gum: a clinical study using quantitative light-induced fluorescence.

PURPOSE: To determine whether sugar-free gum can provide remineralization and caries control of active enamel caries lesions compared to baseline (before gum chewing) and to a no-gum group, following daily chewing for 12 weeks by school children; to determine whether chewing frequency can affect the extent of remineralization. METHOD: A pragmatic cluster-randomized controlled clinical trial with schools as the unit of randomization was employed. Three schools in Chengdu, PR China comprised the clusters. The study was approved by the Internal Review Board of Sichuan University. 177 school children, 8-13 years old, with at least one visible white-spot lesion were enrolled in the study. Each of the three clusters was randomly assigned to one of three groups: (1) no gum; (2) chew 2 pieces of sugar-free gum for 20 minutes, 3x per day; (3) chew 2 pieces of sugar-free gum for 12 minutes, 5x per day. White-spot lesions were examined by quantitative light-induced fluorescence (QLF) at baseline and after 4, 8, and 12 weeks of treatment. RESULTS: 155 subjects completed the study. Of them, the mean values of fluorescence loss at baseline were 9.52, 9.83 and 9.17 for no-gum group, 3x per day group and 5x per day group, respectively. For the area, the mean values at baseline were 2.52, 2.61 and 2.57 mm2 for no-gum group, 3x per day group and 5x per day group, respectively. For AQ, the mean values at baseline were -27.91, -28.29 and -29.67 for no-gum group, 3x per day group and 5x per day group, respectively. To adjust for differences in groups at baseline, ANCOVA was used. After 12-weeks, for all QLF metrics, the absolute values of 5x per day group were the lowest and the no gum group was the highest; the differences among three groups were statistically significant (P < 0.05). For AQ, which was accepted as the most useful metrics of QLF system, the adjusted mean values at 12 weeks were -26.35, -19.81 and -17.58 for no-gum group, 3x per day group and 5x per day group, respectively. There were significant differences between groups.

A Nature-Derived, Hetero-Structured, Pro-Healing Bioadhesive Patch for High-Performance Sealing of Wet Tissues.

Tissue adhesives are promising alternatives to sutures and staples to achieve wound closure and hemostasis. However, they often do not work well on tissues that are soaked in blood or other biological fluids, and organs that are typically exposed to a variety of harsh environments such as different pH values, nonhomogeneous distortions, continuous expansions and contractions, or high pressures. In this study, a nature-derived multilayered hetero-bioadhesive patch (skin secretion of Andrias davidianus (SSAD)-Patch) based on hydrophilic/hydrophobic pro-healing bioadhesives derived from the SSAD is developed, which is designed to form pressure-triggered strong adhesion with wet tissues. The SSAD-Patch is successfully applied for the sealing and healing of tissue defects within 10 s in diverse extreme injury scenarios in vivo including rat stomach perforation, small intestine perforation, fetal membrane defect, porcine carotid artery incision, and lung lobe laceration. The findings reveal a promising new type of self-adhesive regenerative SSAD-Patch, which is potentially adaptable to broad applications (under different pH values and air or liquid pressures) in sutureless wound sealing and healing.

Injectable decellularized dental pulp matrix-functionalized hydrogel microspheres for endodontic regeneration.

The sufficient imitation of tissue structures and components represents an effective and promising approach for tissue engineering and regenerative medicine applications. Dental pulp disease is one of the most common oral diseases, although functional pulp regeneration remains challenging. Herein, we propose a strategy that employs hydrogel microspheres incorporated with decellularized dental pulp matrix-derived bioactive factors to simulate a pulp-specific three-dimensional (3D) microenvironment. The dental pulp microenvironment-specific microspheres constructed by this regenerative strategy exhibited favorable plasticity, biocompatibility, and biological performances. Human dental pulp stem cells (hDPSCs) cultured on the constructed microspheres exhibited enhanced pulp-formation ability in vitro. Furthermore, the hDPSCs-microcarriers achieved the regeneration of pulp-like tissue and new dentin in a semi-orthotopic model in vivo. Mechanistically, the decellularized pulp matrix-derived bioactive factors mediated the multi-directional differentiation of hDPSCs to regenerate the pulp tissue by eliciting the secretion of crucial bioactive cues. Our findings demonstrated that a 3D dental pulp-specific microenvironment facilitated by hydrogel microspheres and dental pulp-specific bioactive factors regenerated the pulp-dentin complex and could be served as a promising treatment option for dental pulp disease. STATEMENT OF SIGNIFICANCE: Injectable bioscaffolds are increasingly used for regenerative endodontic treatment. Despite their success related to their ability to load stem cells, bioactive factors, and injectability, conventional bulk bioscaffolds have drawbacks such as ischemic necrosis in the central region. Various studies have shown that ischemic necrosis in the central region can be corrected by injectable hydrogel microspheres. Unfortunately, pristine microspheres or microspheres without dental pulp-specific bioactive factor would oftentimes fail to regulate stem cells fates in dental pulp multi-directional differentiation. Our present study reported the biofabrication of dental pulp-derived decellularized matrix functionalized gelatin microspheres, which contained dental pulp-specific bioactive factors and have the potential application in endodontic regeneration.

Systemic antibiotics increase microbiota pathogenicity and oral bone loss.

Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.

Perceived impact of the COVID-19 pandemic on infection containment training and mental state of dental residents in China: A longitudinal study.

Background: COVID-19 has presented a challenge for dental settings and dental schools: how to continue providing dental care and maintain education during the pandemic while remaining healthy. We highlight the necessity of infection containment control training for dental residents and rethink the tasks of safeguarding trainees' health and cultivating their abilities to deal with public health crises in the future. This paper may also serve as a health policy reference for policy makers. Objective: The study aimed to compare the formats, frequency, contents, emphasis, and test scores of infection containment control training pre- and post-pandemic. Besides, after the COVID-19 outbreak, we assessed the increased anxiety level, communication difficulties, and confidence of dental residents impacted by the pandemic. Methods: A total of 251 dental residents in Stomatological Hospital of Chongqing Medical University were recruited to complete a questionnaire of their routine involvement in infection control training before and after the COVID-19 outbreak. A self-designed 10-point Likert scale was used to assess the increased anxiety level, communication difficulties, and confidence in facing with the future public health crisis impacted by the pandemic. Results: After the outbreak, although more trainees chose online assessment than offline assessment, most of them (74.90%) still preferred in-person training rather than online training. Contents that trainees had been focusing on were affected by the COVID-19 outbreak. Thereafter, they were more inclined to learn crisis management. Over half of the participants (56.17%) participated in training more frequently after the outbreak. However, postgraduate students participated in training less frequently than others after the outbreak (p < 0.01). First-year trainees accounted for the majority in the population who emphasized considerably on infection control training and whose test scores had increased after the outbreak. In addition, the percentage of women scoring increasingly in post-pandemic assessment was significantly higher than that of men. In this study, the average increased anxiety level caused by COVID-19 was 5.51 ± 2.984, which was positively related to communication difficulties with patients caused by the pandemic. The trainees whose homes were located in Hubei Province showed higher increased anxiety levels (8.29 ± 2.93) impacted by the pandemic than the trainees from other provinces (p < 0.05). However, the former's confidence in coping with future public health crises was not significantly different from that of others (p > 0.05). Conclusions: Owing to the impact of COVID-19, the contents that the trainees focused on, frequency, emphasis, and test scores of infection containment control training were changed. Some recommendations have been provided for policy makers to attach importance to crisis-based training to cultivate dental residents in the post-pandemic era.

Correction: Antimicrobial peptide modification enhances the gene delivery and bactericidal efficiency of gold nanoparticles for accelerating diabetic wound healing.

Correction for 'Antimicrobial peptide modification enhances the gene delivery and bactericidal efficiency of gold nanoparticles for accelerating diabetic wound healing' by Song Wang et al., Biomater. Sci., 2018, 6, 2757-2772, DOI: 10.1039/C8BM00807H.

A rational synthesis of ultrasmall palladium-based alloys with superhydrophilicity as biocompatible agents and recyclable catalysts.

As essential controlling parameters, the local surface area (size distribution) and polarity property of the surface molecules can determine the catalytic activity and biocompatibility directly. Here, ultrasmall palladium-based alloys (FePd, FePdCo, and FePdCu NCs) were developed to serve as artificial degradation catalysts with superhydrophilicity (SPh), biocompatibility, and reusability, which were referred to as "biocatalysts". As synthesized in aqueous solvent with negative surface potential while dispersing in water medium, because of the surface biological molecules effect. The obtained alloys illustrated a size distribution of about 3.5 nm. Additionally, owing to SPh property, these alloys could be stored in water up to 30 days without any precipitation and retained their monodisperse morphology in colloidal solutions. The cytotoxicity assessment of the alloys by exposing to L-929 cells over 3 days indicated that it maintained cell viability of >80% even up to 390 µg mL-1 (concentration of alloys). Furthermore, they exhibited an obvious enhancement in the catalytic performance for degrading Rhodamine B (RhB) and 4-nitrophenol (4-NP). The recyclable utilization of biocatalysts demonstrates durable stability even after 8 reduction cycles.

Combination wound healing using polymer entangled porous nanoadhesive hybrids with robust ROS scavenging and angiogenesis properties.

Nanoadhesives can achieve tight wound closure by connecting biomacromolecules from both sides. However, previously developed adhesive systems suffered from suboptimal wound healing efficiency due to the lack of interparticle cohesion, sufficient reactive oxygen species (ROS)-scavenging sites, and angiogenesis consideration. Herein, we developed a polymer entangled porous nanoadhesive system to address the above challenge by synergy of three functional components. Firstly, hybrid mesoporous silica nanoparticles with highly integrated polydopamine (MS-PDA) were prepared by templated synthesis. The entangling between PVA polymer and MS-PDA contributed to much stronger cohesion between nanoparticles, which led to 75% larger adhesion strength. As confirmed by in vitro and in vivo evaluations, the highly exposed catechol groups boosted the scavenging activity of ROS (1.8-4.1 fold enhancement as compared with nonporous counterpart). Consequently, more macrophages exhibited anti-inflammatory phenotype, leading to 2-2.6 fold lower pro-inflammatory cytokine levels. Moreover, the sustained release of bioactive SiO44- by the disintegration of nanoparticles contributed to ∼3-fold higher expression of VEGF and enhanced new blood vessel formation, as well as better wound repair. This platform can provide a new paradigm for developing multifunctional nanoadhesive systems in treating skin wounds. STATEMENT OF SIGNIFICANCE: PVA polymer entangled mesoporous nanoadhesives of polydopamine (PDA)/silica hybrids with the combination of excellent wound closure effect, boosted ROS-scavenging activity, and significant angiogenesis ability were developed for improving the suboptimal skin wound healing efficiency. This strategy not only greatly advances our ability to rationally integrate repairing elements in nanoadhesives for manipulating combined processes of interfacial events during wound healing, but also offers general implications toward application of polymers to reinforce the adhesion strength in nanoadhesive systems. In addition, our findings on the impacts of pore effects mediated ROS species conversion and polymer entanglement may also trigger great interests and facilitate the development/broad application of therapeutic adhesives.

Bioinspired Andrias davidianus-Derived wound dressings for localized drug-elution.

Local drug delivery has received increasing attention in recent years. However, the therapeutic efficacy of local delivery of drugs is still limited under certain scenarios, such as in the oral cavity or in wound beds after resection of tumors. In this study, we introduce a bioinspired adhesive hydrogel derived from the skin secretions of Andrias davidianus (SSAD) as a wound dressing for localized drug elution. The hydrogel was loaded with aminoguanidine or doxorubicin, and its controlled drug release and healing-promoting properties were verified in a diabetic rat palatal mucosal defect model and a C57BL/6 mouse melanoma-bearing model, respectively. The results showed that SSAD hydrogels with different pore sizes could release drugs in a controllable manner and accelerate wound healing. Transcriptome analyses of the palatal mucosa suggested that SSAD could significantly upregulate pathways linked to cell adhesion and extracellular matrix deposition and had the ability to recruit keratinocyte stem cells to defect sites. Taken together, these findings indicate that property-controllable SSAD hydrogels could be a promising biofunctional wound dressing for local drug delivery and promotion of wound healing.

Investigation of Cell Adhesion and Cell Viability of the Endothelial and Fibroblast Cells on Electrospun PCL, PLGA and Coaxial Scaffolds for Production of Tissue Engineered Blood Vessel.

Endothelialization of artificial scaffolds is considered an effective strategy for increasing the efficiency of vascular transplantation. This study aimed to compare the biophysical/biocompatible properties of three different biodegradable fibrous scaffolds: Poly (ɛ-caprolactone) (PCL) alone, Poly Lactic-co-Glycolic Acid (PLGA) alone (both processed using Spraybase® electrospinning machine), and Coaxial scaffold where the fiber core and sheath was made of PCL and PLGA, respectively. Scaffold structural morphology was assessed by scanning electron microscope and tensile testing was used to investigate the scaffold tension resistance over time. Biocompatibility studies were carried out with human umbilical vein endothelial cells (HUVEC) and human vascular fibroblasts (HVF) for which cell viability (and cell proliferation over a 4-day period) and cell adhesion to the scaffolds were assessed by cytotoxicity assays and confocal microscopy, respectively. Our results showed that all biodegradable polymeric scaffolds are a reliable host to adhere and promote proliferation in HUVEC and HVF cells. In particular, PLGA membranes performed much better adhesion and enhanced cell proliferation compared to control in the absence of polymers. In addition, we demonstrate here that these biodegradable membranes present improved mechanical properties to construct potential tissue-engineered vascular graft.

Orf virus DNA vaccines expressing ORFV 011 and ORFV 059 chimeric protein enhances immunogenicity.

BACKGROUND: ORFV attenuated live vaccines have been the main prophylactic measure against contagious ecthyma in sheep and goats in the last decades, which play an important role in preventing the outbreak of the disease. However, the available vaccines do not induce lasting immunity in sheep and goats. On the other hand, variation in the terminal genome of Orf virus vaccine strains during cell culture adaptation may affect the efficacy of a vaccine. Currently, there are no more effective antiviral treatments available for contagious ecthyma. RESULTS: We constructed three eukaryotic expression vectors pcDNA3.1-ORFV011, pcDNA3.1-ORFV059 and pcDNA3.1-ORFV011/ORFV059 and tested their immunogenicity in mouse model. High level expression of the recombinant proteins ORFV011, ORFV059 and ORFV011/ORFV059 was confirmed by western blotting analysis and indirect fluorescence antibody (IFA) tests. The ORFV-specific antibody titers and serum IgG1/IgG2a titers, the proliferation of lymphocytes and ORFV-specific cytokines (IL-2, IL-4, IL-6, IFN-γ, and TNF-α) were examined to evaluate the immune responses of the vaccinated mice. We found that mice inoculated with pcDNA3.1-ORFV 011/ORFV059 had significantly stronger immunological responses than those inoculated with pcDNA3.1-ORFV011, pcDNA3.1-ORFV059, or pcDNA3.1-ORFV011 plus pcDNA3.1-ORFV059. Compared to other vaccine plasmids immunized groups, pcDNA3.1-ORFV011/ORFV059 immunized group enhances immunogenicity. CONCLUSIONS: We concluded that DNA vaccine pcDNA3.1-ORFV011/ORFV059 expressing ORFV011 and ORFV059 chemeric-proteins can significantly improve the potency of DNA vaccination and could be served as more effective and safe approach for new vaccines against ORFV.

3D printing of robust and biocompatible poly(ethylene glycol)diacrylate/nano-hydroxyapatite composites via continuous liquid interface production.

Three-dimensional (3D) printing technology with satisfactory speed and accuracy has been a powerful force in biomaterial processing. Early studies on 3D printing of biomaterials mainly focused on their biocompatibility and cellular viability while rarely attempted to produce robust specimens. Nonetheless, the biomedical applications of polymers can be severely limited by their inherently weak mechanical properties particularly in bone tissue engineering. In this study, continuous liquid interface production (CLIP) is applied to construct 3D objects of nano-hydroxyapatite (n-HA) filled polymeric biomaterials with complex architectures. Notably, the bioactive and osteoconductive n-HA endows the 3D prints of poly(ethyleneglycol)diacrylate (PEGDA) composites with a high compression strength of 6.5 ± 1.4 MPa, about 342% improvement over neat PEGDA. This work demonstrates the first successful attempt on CLIP 3D printing of n-HA nanocomposites, providing a feasible, cost-effective and patient-specific solution to various fields in the biomedical industry.

Degradation and Characterisation of Electrospun Polycaprolactone (PCL) and Poly(lactic-co-glycolic acid) (PLGA) Scaffolds for Vascular Tissue Engineering.

The current study aimed to evaluate the characteristics and the effects of degradation on the structural properties of Poly(lactic-co-glycolic acid) (PLGA)- and polycaprolactone (PCL)-based nanofibrous scaffolds. Six scaffolds were prepared by electrospinning, three with PCL 15% (w/v) and three with PLGA 10% (w/v), with electrospinning processing times of 30, 60 and 90 min. Both types of scaffolds displayed more robust mechanical properties with increased spinning times. The tensile strength of both scaffolds with 90-min electrospun membranes did not show a significant difference in their strengths, as the PCL and PLGA scaffolds measured at 1.492 MPa ± 0.378 SD and 1.764 MPa ± 0.7982 SD, respectively. All membranes were shown to be hydrophobic under a wettability test. A degradation behaviour study was performed by immersing all scaffolds in phosphate-buffered saline (PBS) solution at room temperature for 12 weeks and for 4 weeks at 37 °C. The effects of degradation were monitored by taking each sample out of the PBS solution every week, and the structural changes were investigated under a scanning electron microscope (SEM). The PCL and PLGA scaffolds showed excellent fibre structure with adequate degradation, and the fibre diameter, measured over time, showed slight increase in size. Therefore, as an example of fibre water intake and progressive degradation, the scaffold's percentage weight loss increased each week, further supporting the porous membrane's degradability. The pore size and the porosity percentage of all scaffolds decreased substantially over the degradation period. The conclusion drawn from this experiment is that PCL and PLGA hold great promise for tissue engineering and regenerative medicine applications.