The engineering of tracheal substitutes is pivotal in improving tracheal reconstruction. In this study, we aimed to investigate the effects of biomechanical stimulation on tissue engineering tracheal cartilage by mimicking the trachea motion through a novel radial stretching bioreactor, which enables to dynamically change the diameter of the hollow cylindrical implants. Applying our bioreactor, we demonstrated that chondrocytes seeded on the surface of Poly (ε-caprolactone) scaffold respond to mechanical stimulation by improvement of infiltration into implants and upregulation of cartilage-specific genes. Further, the mechanical stimulation enhanced the accumulation of cartilage neo-tissues and cartilage-specific extracellular macromolecules in the muscle flap-remodeled implants and reconstructed trachea. Nevertheless, the invasion of fibrous tissues in the reconstructed trachea was suppressed upon mechanical loading.

Marketed lidocaine dosage forms (such as ointment, gels, and injections) used to manage acute and chronic pain showed a short duration of action (<2 h). In this study, a lidocaine-loaded cubosomal gel was prepared to sustain the release of lidocaine to prolong the local anesthetic effect (high drug retention in the skin). Lidocaine-loaded cubosomal gels were prepared by melt emulsification and sonication using Pluronic F127 and DL-α-monoolein (at different levels). The cubosomal gels were characterized by morphology, size, zeta potential, entrapment efficacy, assay, viscosity, pH, and texture profiles. Ex vivo lidocaine permeation and retention studies were performed using Sprague-Dawley rat skin. Transmission electron microscopy images confirmed the bi-continuous liquid crystalline phase with a honeycomb cubosome structure. The cubosomal particle size (103-227nm), viscosity (13,524-15,627cp), and entrapment efficacy (78.4-94.7%) increase with the level of monoolein. The ex-vivo permeation study showed a biphasic release pattern, with lidocaine cleared from ointment within 4h (97.9% cumulative release), while cubosomal gels showed sustained release up to 24h (53.33-98.86% cumulative release). A skin retention study demonstrated that cubosomes can increase (up to 28-fold) the lidocaine content in the skin (4.56mg) compared to ointment (0.19mg). A rabbit skin irritation study showed no sign of irritation after the application of cubosomal gel. In the radiant heat tail-flick study, the local anesthetic effect of lidocaine from the cubosomal gel was sustained for up to 16h with 1.43-fold higher efficacy than marketed ointment. In conclusion, the study demonstrated the potential of cubosomal nanoparticle-laden gel to sustain the release of lidocaine for prolonging local anesthetic effects for pain management.

Malignant tumor is one of the major diseases with high morbidity and mortality. The purpose of this study is to prepare berberine hydrochloride (BH) in situ thermo-sensitive hydrogel based on glycyrrhetinic acid (GA) modified nano graphene oxide (NGO) (GA-BH-NGO-gel). NGO was taken as the photosensitizer, GA was taken as the target molecule, and BH was taken as the model drug. The physicochemical properties and anti-tumor activity in vivo and in vitro were also studied. This subject could provide a certain theoretical basis for the chemo-photothermal therapy combined treatment of malignant tumor. The release behavior of GA-BH-NGO-gel in vitro presented sustained and temperature-dependent drug release effect. The anti-tumor activity studies in vivo and in vitro had shown that GA-BH-NGO-gel had stronger anti-tumor activity, which could be targeting distributed to the tumor tissues. Moreover, the inhibitory effect of GA-BH-NGO-gel was enhanced when combined with 808nm of laser irradiation. In this research, the chemo-photothermal combination therapy was applied into the tumor treatment, which may provide certain research ideas for the clinical treatment of malignant tumor.

Traumatic heterotopic ossification (THO) is a serious and common clinical post-traumatic complication for which there is no effective and safe drug treatment. Routine administration of nonsteroidal anti-inflammatory drugs (NSAIDs) after injury is extensively used approach for THO. However, serious adverse events can occur in the event of an overdose of NSAIDs. In our study, we have developed a poly(lactic acid-co-glycolic acid) (PLGA) microsphere by emulsifying solvent volatilization for the prolonged slow delivery of celecoxib (CLX). Three groups of celecoxib-poly(lactic acid-co-glycolic acid) microspheres (CLX-PLGA MPs) were prepared with particle sizes of 3.75±1.28μm, 49.56±17.15μm, and 94.98±42.53μm. Meanwhile, related parameters of microspheres in each group were studied: drug loading (DL), encapsulation rate (EE), and slow-release behavior. The DL and EE of the 3 CLX-PLGA MPs did not vary significantly, and subsequently, we selected the second drug loading microspheres with a retardation period of about 70 days for subsequent experiments. Moreover, cellular and animal experiments suggest that the microspheres are biocompatible and can be safely applied to localized trauma tissue. Finally, it is demonstrated that CLX-PLGA MPs have an effect on inhibiting the osteogenic differentiation of bone marrow mesenchymal stem cells and have the potential to inhibit ectopic bone formation of the THO model in Sprague-Dawley rat. Therefore, this study suggests that CLX-PLGA MPs are expected to be applied topically in the early post-traumatic period to prevent the development of THO.

Tannic Acid (TA) is a naturally occurring antioxidant polyphenol that has gained popularity over the past decade in the field of biomedical research for its unique biochemical properties. Tannic acid, typically extracted from oak tree galls, has been used in many important historical applications. TA is a key component in vegetable tanning of leather, iron gall ink, red wines, and as a traditional medicine to treat a variety of maladies. The basis of TA utility is derived from its many hydroxyl groups and its affinity for forming hydrogen bonds with proteins and other biomolecules. Today, the study of TA has led to the development of many new pharmaceutical and biomedical applications. TA has been shown to reduce inflammation as an antioxidant, act as an antibiotic in common pathogenic bacterium, and induce apoptosis in several cancer types. TA has also displayed antiviral and antifungal activity. At certain concentrations, TA can be used to treat gastrointestinal disorders such as hemorrhoids and diarrhea, severe burns, and protect against neurodegenerative diseases. TA has also been utilized in biomaterials research as a natural crosslinking agent to improve mechanical properties of natural and synthetic hydrogels and polymers, while also imparting anti-inflammatory, antibacterial, and anticancer activity to the materials. TA has also been used to develop thin film coatings and nanoparticles for drug delivery. In all, TA is fascinating molecule with a wide variety of potential uses in pharmaceuticals, biomaterials applications, and drug delivery strategies.

Monitoring the infection behavior of avian influenza viruses is crucial for understanding viral pathogenesis and preventing its epidemics among people. A number of viral labeling methods have been utilized for tracking viral infection process, but most of them are laborious or decreasing viral activity. Herein we explored a lipid biosynthetic labeling strategy for dynamical tracking the infection of H5N1 pseudotype virus (H5N1p) in host. Biotinylated lipids (biotinyl Cap-PE) were successfully incorporated into viral envelope when it underwent budding process by taking advantage of host cell-derived lipid metabolism. Biotin-H5N1p virus was effectively in situ-labeled with streptavidin-modified near-infrared quantum dots (NIR SA-QDs) using streptavidin-biotin conjugation with well-preserved virus activities. Dual-labeled imaging obviously shows that H5N1p viruses are primarily taken up in host cells via clathrin-mediated endocytosis. In animal models, Virus-conjugated NIR QDs displayed extraordinary photoluminescence, superior stability, and tissue penetration in lung, allowing us to long-term monitor respiratory viral infection in a noninvasive manner. Importantly, the co-localization of viral hemagglutinin protein and QDs in infected lung further conformed the dynamic infection process of virus in vivo. Hence, this in situ QD-labeling strategy based on cell natural biosynthesis provides a brand-new and reliable tool for noninvasion visualizing viral infection in body in a real-time manner.

Implant-related infection is a disastrous complication. Surface modification of titanium is considered as an important strategy to prevent implant-related infection. However, there is no recognized surface modification strategy that can be applied in clinic so far. We explored a new strategy of coating. The clindamycin-loaded titanium was constructed by layer-by-layer self-assembly. The release of clindamycin from titanium was detected through high performance liquid chromatography. Different titanium was co-cultured with Staphylococcus aureus for 24h in vitro, then the effect of different titanium on bacterial colonization and biofilm formation was determined by spread plate method and scanning electron microscopy. Cytotoxicity and cytocompatibility of clindamycin-loaded titanium on MC3T3-E1 cells were measured by CCK8. The antibacterial ability of clindamycin-loaded titanium in vivo was also evaluated using a rat model of osteomyelitis. The number of osteoclasts in bone defect was observed by tartrate-resistant acid phosphatase staining. Bacterial burden of surrounding tissues around the site of infection was calculated by tissue homogenate and colony count. Clindamycin-loaded titanium could release clindamycin slowly within 160h. It reduced bacterial colonization by three orders of magnitude compare to control (p < .05) and inhibits biofilm formation in vitro. Cells proliferation and adhesion were similar on three titanium surfaces (p > .05). In vivo, clindamycin-loaded titanium improved bone healing, reduced microbial burden, and decreased the number of osteoclasts compared control titanium in the rat model of osteomyelitis. This study demonstrated that clindamycin-loaded titanium exhibited good biocompatibility, and showed antibacterial activity both in vivo and in vitro. It is promising and might have potential for clinical application.

Wound dressings play a vital role in the wound healing process. Although a variety of wound dressings have been developed so far, most of them still have many drawbacks such as rigidity, non-porosity, low mechanical strength, an affinity to stick onto the injury surface and less antimicrobial activity. To overcome these issues, a novel type of porous three-dimensional (3D) film was fabricated using chitosan/carboxymethyl pullulan polyelectrolyte complex (PEC) loaded with 45S5 bioglass (CCMPBG) by the freeze-drying method for wound healing application. The developed films were analysed by FTIR, XRD, EDS and SEM to confirm their chemical nature, microstructure and surface morphologies. The CCMPBG films exhibited rough surface morphology and well-interconnected micropores with an average size range of 101-74μm. Compared to the control chitosan/carboxymethyl pullulan (CCMP) film, the CCMPBG films showed an enhanced mechanical strength and controlled rate of swelling and biodegradation behaviours due to the interaction of polymer matrix and 45S5 bioglass (BG). Furthermore, CCMPBG films presented the improved biocompatibility, antimicrobial activity and wound closure ability because of the synergistic effects of chitosan, carboxymethyl pullulan (CMP) and BG. The results demonstrated that CCMPBG films can be an effective dressing material for wound therapy.

Numerous treatment methods for peri-implantitis have been widely used including oral cleaning, traditional metal scraping means, or local antibiotic application. However, to continuously release antibacterial and anti-inflammatory drug in location in situ for effective peri-implantitis repair is still challenging. Herein, an anti-inflammatory drug dexamethasone (DE)-incorporated hyaluronic acid (HA)-chitosan (CT) composite hydrogels system was developed to repair peri-implantitis. The physicochemical characterization and biocompatibility of the hydrogel were evaluated in vitro. The in vivo hydrogels degradation and peri-implantitis repair were assessed in mice. The results showed that the prepared multifunctional hydrogels achieved sustained release, with an equilibrium swelling of 18, and promoted the growth against NIH-3T3 fibroblast cells. The in vitro antibacterial tests showed HA-CT-DE hydrogels can inhibit methicillin-resistant Staphylococcus aureus and Escherichia coli. It down-regulated the expression levels of inflammation factor IL-1β, IL-6 and, TNF-α in peri-implantitis. The prepared HA-CT-DE composite hydrogels with integrated function is promising for the treatment of peri-implantitis.

It is now generally accepted that 2D cultures cannot accurately replicate the richenvironment and complex tissue architecture that exists in vivo, and that classicallycultured cells tend to lose their original function. Growth of spheroids as opposed to 2Dcultures on plastic has now been hailed as an efficient method to produce quantities ofhigh-quality cells for cancer research, drug discovery, neuroscience, and regenerativemedicine. We have developed a new recombinant protein that mimics dragline spidersilk andthat self-assembles into cell-sized coils. These have high thermal and shelf-lifestability and can be readily sterilized and stored for an extended period of time. Thefibers are flexible, elastic, and biocompatible and can serve as cell-sized scaffold forthe formation of 3D cell spheroids. As a proof of concept, recombinant spidersilk wasintegrated as a scaffold in spheroids of three cell types: primary rat hepatocytes, humanmesenchymal stem cells, and mouse L929 cells. The scaffolds significantly reduced spheroidshrinkage and unlike scaffold-free spheroids, spheroids did not disintegrate over thecourse of long-term culture. Cells in recombinant spidersilk spheroids showed increasedviability, and the cell lines continued to proliferate for longer than control cultureswithout spidersilk. The spidersilk also supported biological functions. Recombinantspidersilk primary hepatocyte spheroids exhibited 2.7-fold higher levels of adenosinetriphosphate (ATP) continued to express and secrete albumin and exhibited significantlyhigher basal and induced CYP3A activity for at least 6 weeks in culture, while controlspheroids without fibers stopped producing albumin after 27 days and CPY3A activity wasbarely detectable after 44 days. These results indicate that recombinant spidersilk canserve as a useful tool for long-term cell culture of 3D cell spheroids and specificallythat primary hepatocytes can remain active in culture for an extended period of time whichcould be of great use in toxicology testing.