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Metformin is a widely used drug for type 2 diabetes mellitus and has recently attracted broad attention for its therapeutic effects on many cancers. This study aimed to investigate the molecular mechanism of metformin's anticancer activity.Cell viability was measured by MTT assay. Gene and protein expression levels were determined by reverse transcription-polymerase chain reaction and western blot analyses, respectively.Metformin and phenformin markedly induced NUPR1 expression in a dose- and time-dependent manner in H1299 non-small-cell lung cancer (NSCLC) cells. The silencing of NUPR1 in H1299 NSCLC cells enhanced cell sensitivity to metformin or ionizing radiation. Our previous report showed that metformin induces AKT serine/threonine kinase (AKT) activation in an activating transcription factor 4 (ATF4)-dependent manner and that the inhibition of AKT promotes cell sensitivity to metformin in H1299 NSCLC cells. Interestingly, ATF4-induced AKT activation in H1299 NSCLC cells treated with metformin was suppressed by the knockdown of NUPR1.Targeting NUPR1 could enhance the sensitivity of H1299 NSCLC cells to metformin by AKT inhibition.

Background Although the use of cardiac patches is still controversial, cardiac patch has the significance in the field of the tissue engineered cardiac regeneration because it overcomes several shortcomings of intra-myocardial injection by providing a template for cells to form a cohesive sheet. So far, fibrous scaffolds fabricated using electrospinning technique have been increasingly explored for preparation of cardiac patches. One of the problems with the use of electrospinning is that nanofibrous structures hardly allow the infiltration of cells for development of 3D tissue construct. In this respect, we have prepared novel bi-modal electrospun scaffolds as a feasible strategy to address the challenges in cardiac tissue engineering . Methods Nano/micro bimodal composite fibrous patch composed of collagen and poly (D, L-lactic-co-glycolic acid) (Col/PLGA) was fabricated using an independent nozzle control multi-electrospinning apparatus, and its feasibility as the stem cell laden cardiac patch was systemically investigated. Results Nano/micro bimodal distributions of Col/PLGA patches without beaded fibers were obtained in the range of the 4-6% collagen concentration. The poor mechanical properties of collagen and the hydrophobic property of PLGA were improved by co-electrospinning. In vitro experiments using bone marrow-derived mesenchymal stem cells (BMSCs) revealed that Col/PLGA showed improved cyto-compatibility and proliferation capacity compared to PLGA, and their extent increased with increase in collagen content. The results of tracing nanoparticle-labeled as well as GFP transfected BMSCs strongly support that Col/PLGA possesses the long-term stem cells retention capability, thereby allowing stem cells to directly function as myocardial and vascular endothelial cells or to secrete the recovery factors, which in turn leads to improved heart function proved by histological and echocardiographic findings. Conclusion Col/PLGA bimodal cardiac patch could significantly attenuate cardiac remodeling and fully recover the cardiac function, as a consequence of their potent long term stem cell engraftment capability.

G protein–coupled receptors (GPCRs) are a diverse family of cell surface receptors implicated in various physiological functions, making them common targets for approved drugs. Many GPCRs are abnormally activated in cancers and have emerged as therapeutic targets for cancer. Neuropeptide FF receptor 2 (NPFFR2) is a GPCR that helps regulate pain and modulates the opioid system; however, its function remains unknown in cancers. Here, we found that NPFFR2 is significantly up-regulated in liver cancer and its expression is related to poor prognosis. Silencing of NPFFR2 reduced the malignancy of liver cancer cells by decreasing cell survival, invasion, and migration, while its overexpression increased invasion, migration, and anchorage-independent cell growth. Moreover, we found that the malignant function of NPFFR2 depends on RhoA and YAP signaling. Inhibition of Rho kinase activity completely restored the phenotypes induced by NPFFR2, and RhoA/F-Actin/YAP signaling was controlled by NPFFR2. These findings demonstrate that NPFFR2 may be a potential target for the treatment of hepatocellular carcinoma.

Because various stimuli can affect living organisms, substances that response to stimuli, such as H2O2, have been studied for biomaterials. To synthesize a biocompatible H2O2-responsive ionic cross-linker, we synthesized a water-soluble H2O2-responsive diselenide compounds containing both sulfate end groups (diSe-SO4). The synthesis of diSe-SO4 was evaluated by 1H NMR and FT-IR. H2O2 responsiveness was evaluated by UV–vis spectra, FT-IR, and XPS. The optical density at 303 nm due to diselenide in diSe-SO4 was decreased in the H2O2 concentration increased. FT-IR and XPS results showed new peaks at 880 cm and 3500 cm−1, and at 63.0 eV, respectively, due to oxidized Se, which indicated the cleavage of the diselenide bond in diSe-SO4 as the H2O2 concentration increased. The ionic binding efficiency of diSe-SO4 to cationic materials was confirmed by measuring the zeta-potential difference (from –15.6 mV to 10.3 mV) before and after mixing with chitosan. MRC-5 cell viability and apoptosis in the presence of diSe-SO4 was evaluated using a CCK-8 assay and FACS, respectively. A high cell viability exceeding 95% was observed at 500 μM diSe-SO4 over 48 h of culture. In conclusion, the synthesized water-soluble diSe-SO4 provides a H2O2-responsive ionic cross-linking material with a high cell affinity.

Although endocrine therapy with tamoxifen has improved survival in breast cancer patients, resistance to this therapy remains one of the major causes of breast cancer mortality. In the present study, we found that the expression level of YAP/TAZ in tamoxifen-resistant MCF7 (MCF7-TR) breast cancer cells was significantly increased compared with that in MCF7 cells. Knockdown of YAP/TAZ with siRNA sensitized MCF7-TR cells to tamoxifen. Furthermore, siRNA targeting PSAT1, a downstream effector of YAP/TAZ, enhanced sensitivity to tamoxifen in MCF7-TR cells. Additionally, mTORC1 activity and survivin expression were significantly decreased during cell death induced by combination treatment with YAP/TAZ or PSAT1 siRNA and tamoxifen. In conclusion, targeting the YAP/TAZ-PSAT1 axis could sensitize tamoxifen-resistant MCF7 breast cancer cells by modulating the mTORC1-survivin axis.

Gelatin has excellent biological properties, but its poor physical properties are a major obstacle to its use as a biomaterial ink. These disadvantages not only worsen the printability of gelatin biomaterial ink, but also reduce the dimensional stability of its 3D scaffolds and limit its application in the tissue engineering field. Herein, biodegradable suture fibers were added into a gelatin biomaterial ink to improve the printability, mechanical strength, and dimensional stability of the 3D printed scaffolds. The suture fiber reinforced gelatin 3D scaffolds were fabricated using the thermo-responsive properties of gelatin under optimized 3D printing conditions (−10 °C cryogenic plate, 40–80 kPa pneumatic pressure, and 9 mm/s printing speed), and were crosslinked using EDC/NHS to maintain their 3D structures. Scanning electron microscopy images revealed that the morphologies of the 3D printed scaffolds maintained their 3D structure after crosslinking. The addition of 0.5% (w/v) of suture fibers increased the printing accuracy of the 3D printed scaffolds to 97%. The suture fibers also increased the mechanical strength of the 3D printed scaffolds by up to 6-fold, and the degradation rate could be controlled by the suture fiber content. In in vitro cell studies, DNA assay results showed that human dermal fibroblasts’ proliferation rate of a 3D printed scaffold containing 0.5% suture fiber was 10% higher than that of a 3D printed scaffold without suture fibers after 14 days of culture. Interestingly, the supplement of suture fibers into gelatin biomaterial ink was able to minimize the cell-mediated contraction of the cell cultured 3D scaffolds over the cell culture period. These results show that advanced biomaterial inks can be developed by supplementing biodegradable fibers to improve the poor physical properties of natural polymer-based biomaterial inks.

Biocompatible and biodegradable gelatin is a good candidate bioink for use in 3D bioprinting technologies, but viscous gelatin solution has a low printability. In order to improve the poor printability of gelatin, we optimized the rheological properties of gelatin solution. 3D gelatin scaffolds were then cross-linked using physical or chemical methods to maintain the 3D structure. The physicochemical and biological differences between the two types of cross-linked gelatin scaffolds were studied. Scanning electron microscopy images revealed that the morphologies of the resulting cross-linked 3D scaffolds maintained their structural stabilities. The physically cross-linked 3D scaffolds maintained their surface sizes without a significant decrease (less than a 3% reduction in the surface size was observed) after cross-linking. To evaluate the differences in cell affinity by two types of cross-linking method, human dermal fibroblasts cultured on the cross-linked 3D scaffolds. After 14 days of culturing, DNA assays showed that the cell proliferation rate of the physically cross-linked 3D scaffold was 44% higher than that of the chemically cross-linked 3D scaffold. In conclusion, the optimized physically cross-linked 3D scaffold retained its surface size without significant decreases after cross-linking, as required by 3D-printed patient-specific tissue engineered customized scaffolds, despite the use of water-soluble gelatin hydrogels.

Although chitosan is the second most abundant natural polymer on earth, with a wide range of biomaterial applications, its poor water solubility limits general printing process. We selected water-soluble methacrylated glycol chitosan (MeGC) as an alternative and prepared a MeGC-based MG-63 cell-laden bioink for 3D printing using a visible light curing system. Optimal cell-laden 3D printing of MeGC was completed at 3% using 12 μM of riboflavin as a photoinitiator under an irradiation for 70 s, a 26-gauge nozzle, a pneumatic pressure of 120 kPa, and a printing speed of 6 mm/s, as confirmed by printability, protein adsorption, cell viability, cell proliferation, and osteogenic capability. In addition, in vitro tests showed that MeGC-70 has a viability above 92%, a proliferation above 96%, and a hemolysis level below 2%. The results demonstrate the potential for MeGC-70 bioinks and 3D printed scaffolds to be used as patient-specific scaffolds for bone regeneration purposes.

Significant efforts have been applied toward fabricating three-dimensional (3D) scaffolds using 3D-bioprinting tissue engineering techniques. Gelatin has been used in 3D-bioprinting to produce designed 3D scaffolds; however, gelatin has a poor printability and is not useful for fabricating desired 3D scaffolds using 3D-bioprinting. In this study, we fabricated pore size controlled 3D gelatin scaffolds with two step 3D-bioprinting approach: a low-temperature (−10 °C) freezing step and a crosslinking process. The scaffold was crosslinked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). The pore sizes of the produced 3D gelatin scaffolds were approximately 30% smaller than the sizes of the designed pore sizes. The surface morphologies and pore sizes of the 3D gelatin scaffolds were confirmed and measured using scanning electron microscopy (SEM). Human dermal fibroblasts (HDFs) were cultured on a 3D gelatin scaffold to evaluate the effect of the 3D gelatin scaffold pore size on the cell proliferation. After 14 days of culture, HDFs proliferation throughout the 3D gelatin scaffolds prepared with more than 580 μm pore size was approximately 14% higher than proliferation throughout the 3D gelatin scaffold prepared with a 435 μm pore size. These results suggested that control over the 3D gelatin scaffold pore size is important for tissue engineering scaffolds.

In this study, we first prepared the precursor polytetrafluoroethylene (PTFE)/poly(ethylene oxide) (PEO) nanofibrous membranes by electrospinning with different PTFE/PEO weight ratios. These membranes exhibited three-dimensional interconnected pore structures. The average diameter of the precursor nanofibres decreased with increased PTFE contents from 633 ± 34 nm (PTFE/PEO weight ratio of 5 : 1) to 555 ± 63 nm (PTFE/PEO weight ratio of 7 : 1) because of the decrease in solution viscosity. Then, the precursor membranes were sintered with different temperatures to obtain the PTFE nanofibrous membranes, resulting in the average diameter of the nanofibres increasing from 633 ± 34 nm to 947 ± 78 nm with the increase in sintering temperature; consequently, the membrane became more compact. This compaction caused a decrease in porosity from 76.5 ± 2.9% to 69.1 ± 2.6% and an increase in water contact angle from 94.1 ± 4.2° to 143.3 ± 3.5°. In addition, the mechanical properties of the PTFE nanofibrous membranes increased with increasing sintering temperature. Cytocompatibility test results revealed that the PTFE350 membrane, which was sintered at 350 °C, promoted the proliferation and differentiation of MC3T3-E1 cells more rapidly than other membrane types. These results suggested that the PTFE nanofibrous membranes could be ideal biomaterials in tissue engineering for bone regeneration.

[Purpose] Recent evidence suggests that regular exercise training plays a decisive role in maintaining homeostasis and promoting muscle and skeletal formation. However, the effect of downhill exercise training on osteogenesis-related factors is not well understood. [Methods] Thus, we investigated the effect of uphill and downhill training on ovariectomy (OVX)-induced bone loss. After ovary removal, the exercise method performed included uphill (16 m/min, +15°) and downhill training (16 m/min, –15°) for 60 min/day and 5 days/week, respectively, for 8 weeks. [Results] Our results showed that both uphill and downhill training significantly decreased the body weight, total cholesterol, and creatine kinase (CK) levels in the context of OVX-induced bone loss. On the contrary, levels of an osteogenesis indicator, osteocalcin and alkaline phosphatase were elevated. Consequently, the uphill and downhill training reduced OVX- induced bone loss in the distal femoral metaphysis. Likewise, the bone microstructure in OVX-induced bone loss was enhanced upon training. In particular, the inhibition of RANKL-induced osteoclast formation and osteoclast-specific gene expression improved upon downhill training compared to uphill training. [Conclusion] These results suggest that the uphill and downhill exercise types appeared to positively affect the expression of osteogenesis-related factors along with bone density and microstructure. Particularly, the downhill training has more beneficial effects on the maintenance of homeostasis during bone formation.

The visible light-cured glycol chitosan (GC) hydrogel systems for the sustained release of growth factors (GFs) were prepared, and their efficacies in wound healing acceleration were investigated. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor-BB (PDGF-BB) were selected as the dual GFs and commercially available Duoderm® was used as control. In order to increase intermolecular chain mobility, methoxy (polyethylene glycol) acetic acid (MPEG-COOH) was conjugated to GC through condensation reaction resulting in MPEG grafted GC (MPEG-g-GC). As a crosslinker, glycidyl methacrylate was covalently conjugated to the amine group of MPEG-g-GC (MPEG/GM-g-GC), and crosslinking of MPEG/GM-g-GC chains were made by visible light irradiation (MPEG-g-GC hydrogels). To enhance wound healing efficacy, specific amounts of GFs was incorporated into the crosslinking solutions at this photo-curing stage (VEGF/MPEG-g-GC, PDGF/MPEG-g-GC and VEGF/PDGF/MPEG-g-GC). The grafting of MPEG plasticized the samples yielding low viscoelastic properties, ranging from 56 Pa to 58 Pa. In vitro release test showed that GFs were rapidly released within 24 h, and released in a sustained manner thereafter. In vivo studies showed that the GF-loaded samples further enhanced wound healing compared to control. Particularly, VEGF/PDGF/MPEG-g-GC, dual GFs releasing hydrogel, showed outstanding granulation effects among samples.

Chlorin e6 (Ce6), with its high phototoxic potential, has wide applications in photodynamic therapy (PDT) for many human diseases. However, poor cancer cell localization of Ce6 has limited its direct application for PDT. Here, we developed cancer-targeting peptide p 18-4/chlorin e6 (Ce6)-conjugated polyhedral oligomeric silsesquioxane (PPC) nanoparticles for improving the targeting ability of Ce6 to breast cancer cells, thereby enhancing PDT efficacy. The synthesized PPC nanoparticles exhibited a spherical shape with an average diameter of 127.2 ± 11.3 nm in aqueous solution. Compared with free Ce6, the immobilization of p 18-4 enhanced the in vitro cellular uptake and targeting ability of PPC nanoparticles in breast cancer cell line MDA-MB-231. In addition, the intracellular uptake of PPC nanoparticles in MDA-MB-231 cells was dramatically increased compared with other cancer cells, indicating an obvious targeting ability of PPC nanoparticles on breast cancer cells. Upon light irradiation, PPC nanoparticles revealed significantly improved phototoxicity to MDA-MB-231 cells, mainly due to apoptotic cell death. In vivo PDT study suggested that PPC nanoparticles exhibited increased retention in tumor tissues and effectively inhibited the growth of MDA-MB-231 tumors in a target-specific manner. Overall, these results indicate that PPC nanoparticles are highly effective PDT agents for breast cancer therapy.

In this study, we prepared poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) conjugated to lysyl oxidase-inhibiting antibodies (LOXab) as an anticancer therapy in order to efficiently inhibit the growth of mammary cancer cells. Scanning electron microscopy and dynamic light scattering analysis showed that the antibody-conjugated NPs tested were stable and round, with a mean diameter of 165 nm and surface charge of -15 mV, compared with values of 143 nm and -17 mV for pristine NPs. The pristine NPs at concentrations less than 1,000 ug/ml showed low cytotoxicity and were effectively internalized into cancer cells. Our in vitro studies showed that the LOXab conjugated NPs were two to three times more suppressive of lung, colorectal and breast cancer cells than was the soluble antibody at the same dose. Taken together, our results suggest that NPs conjugated to LOXab constitute a promising nano-therapeutic candidate for inhibiting the growth of mammary cancer cells.

Lung fibrosis is a major complication in radiation-induced lung damage following thoracic radiotherapy, while the underlying mechanism has remained to be elucidated. The present study performed immunofluorescence and immunoblot assays on irradiated human pulmonary artery endothelial cells (HPAECs) with or without pre-treatment with VAS2870, a novel NADPH oxidase (NOX) inhibitor, or small hairpin (sh)RNA against NOX1, -2 or -4. VAS2870 reduced the cellular reactive oxygen species content induced by 5 Gy radiation in HPAECs and inhibited phenotypic changes in fibrotic cells, including increased alpha smooth muscle actin and vimentin, and decreased CD31 and vascular endothelial cadherin expression. These fibrotic changes were significantly inhibited by treatment with NOX1 shRNA, but not by NOX2 or NOX4 shRNA. Next, the role of NOX1 in pulmonary fibrosis development was assessed in the lung tissues of C57BL/6J mice following thoracic irradiation using trichrome staining. Administration of an NOX1-specific inhibitor suppressed radiation-induced collagen deposition and fibroblastic changes in the endothelial cells (ECs) of these mice. The results suggested that radiation-induced pulmonary fibrosis may be efficiently reduced by specific inhibition of NOX1, an effect mediated by reduction of fibrotic changes of ECs.

When assessing crack initiation of fiber reinforced concrete, usually tensile strength or flexural strength is becomes indicato r, but also depend on the curing effect take place during the production of specimen. In general, after conducting concrete specimen is cured by w ater at temperature 20±3°C in laboratory, and accomplished the assessment of strength, but most of concrete structure is kept in drying condition a fter moist curing through the prescribed period. However, unlike these trends that technological advances have been made, influence of the difference of curing method on crack strength is not yet clear. Therefore, in this study, it is examined on the effect of curing methods affecting the mechanical pr operty of fiber reinforced concrete, especially crack strength.Keywords: Crack strength, Curing method, Fiber, Fiber reinforced concrete, Mechanical property 1 정회원, 중부대학교 토목공학과 교수 2 정회원 , 전북대학교 토목공학과 부교수교신저자*Corresponding author: asahi00@jbnu.ac.kr∙본 논문에 대한 토의를 2016년 4월 1일까지 학회로 보내주시면 2016년 5월호에 토론결과를 게재하겠습니다.Copyright Ⓒ 2016 by The Korea Institute for Structural Maintenance and Inspection. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0)which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

In recent years, in terms of environmental protection and efficient use of the land, efficient utilization of byproducts and wastes generated in industrial areas are emerging. In this study, for the effective utilization of using ever increasing amount of utilizing sewage sludge incineration ash to increase sewage sludge, it is evaluated the use of as an construction material. After making concrete specimens, it is evaluated compressive strength, carbonation and environmental resistance. From the experimental results, compared with concrete without sewage sludge it is obtained satisfactory results for compressive strength and carbonation and results of the leaching test also satisfies the standard value. So, it is sufficient possibility using of concrete aggregate and the replacement rates is judged to be about 10%.

An analytical study was conducted to investigate the effect of the shape and spacing of modified inclined studs used as shear connector between concrete and steel plate on the cyclic behavior of steel plate concrete (SC) shear wall. 9 different analysis cases were adopted to determine the optimized shape and spacing of stud. As the results, the skeleton curves were obtained from the load-displacement hysteresis curves, and the ultimate and yielding strengths were increased as the spacing of studs decrease. In addition, the strength of inclined studs is shown to be bigger compared to that of conventional studs. The damping ratios increased as the decrease of stiffness ratio. Finally, with decreasing the spacing distance of studs, the cumulative dissipated energy was increased and the seismic performance was improved.

Growth differentiation factor 15 (GDF15) is an emerging biomarker of cardiovascular risk and disease. Microarray analyses revealed that GDF15 levels were increased during cellular senescence induced by ionizing radiation (IR) in human aortic endothelial cells (HAECs). However, the role of GDF15 in HAEC cellular senescence remains unclear. This study demonstrated that downregulation of GDF15 in HAECs partially prevented cellular senescence triggered by IR, which was confirmed by recovery of cell proliferation and reverse senescence-associated β-galactosidase (SA-β-gal) staining. Conversely, upregulation of GDF15-induced cellular senescence in HAECs, confirmed by G0/G1 cell cycle arrest, decreased during cell proliferation and increased SA-β-gal staining. GDF15-induced cellular senescence was observed in p16-knockdown cells but not in p53-knockdown cells. GDF15 expression in endothelial cells also generated reactive oxygen species (ROS), which led to activation of extracellular signal-regulated kinases (ERKs) and induction of senescence by oxidative stress. These results suggested that GDF15 might play an important role in cellular senescence through a ROS-mediated p16 pathway and contribute to the pathogenesis of atherosclerosis via pro-senescent activity.

To improve the hemostatic function of chitosan nanofiber mats, we studied the synergetic effects of gelatin blending and porosity control. Gelatin-blended-chitosan (Chi-Gel) nanofiber mats were evaluated with respect to surface morphology, mechanical properties and wettability, and functionally tested in a blood clotting study. The blood clotting efficiency of Chi-Gel nanofiber mats using rabbit whole blood in vitro was superior to that of chitosan nanofibers. Moreover, Chi-Gel nanofiber mats with enlarged porosity, produced by ultra-sonication, showed improved blood clotting efficiency, cell viability and cell infiltration compared with non-sonicated Chi-Gel nanofiber mats. Field-emission scanning electron microscopy revealed a richer density of platelets on sonicated nanofiber mats than on non-sonicated nanofiber mats after 3 min of blood clotting. The proliferation of human dermal fibroblast cells on sonicated Chi-Gel nanofiber mats using the DNA assay was higher than that on non-sonicated chitosan nanofiber mats after 7 days of culture. Confocal z-stack images showed that sonicated Chi-Gel nanofiber mats with high porosity supported active cell migration and infiltration into the 3-dimensional nanofiber mats. These results suggest that hydrophilic gelatin blending and sonication of chitosan nanofiber mats yields synergistic effects that not only improve hemostatic function but also promote wound repair.

Lysyl oxidase (LOX) is a cell-secreted amine oxidase that crosslinks collagen and elastin in extracellular microenvironment. LOX-traceable nanoparticles (LOXab-NPs) consisting of LOX antibodies (LOXab) and paclitaxel, can accumulate at high concentrations at radiation-treated target sites, as a tumor-targeting drug carrier for chemotherapy. Tumor-targeting and anticancer effects of PLGA based LOXab-NPs in vitro and in vivo were evaluated at radiation-targeted site. In the in vivo A549 lung carcinoma xenograft model, we showed highly specific tumor targeting (above 7.0 times higher) of LOXab-NPs on irradiated tumors. Notably, systemically administered NPs delayed tumor growth, reducing tumor volumes by more than 2 times compared with non-irradiated groups (222% vs. >500%) over 2 weeks. Radiotropic LOXab-NPs can serve as chemotherapeutic vehicles for combined targeted chemo-radiotherapy in clinical oncology.

Heme oxygenase-1 (HO-1) is a stress-response protein with potent cytoprotective and antioxidant activity, and its expression in cancer cells is enhanced in response to chemotherapy and radiotherapy. HO-1 is known to serve as a shield to protect cancer cells from anticancer therapy and attenuate apoptotic signals. It can be therefore reasoned that inhibition of HO-1 reduces the antioxidant level, making cancer cells more sensitive to photothermal heating. In this work, we developed dual imaging-guided oxidative-photothermal combination nanotherapeutics (OPCN) consisting of amphiphilic polymers conjugated with zinc protoporphyrin as a HO-1 inhibitor and fluorescent IR820 as a photothermal agent. A combination of OPCN and near-infrared (NIR) laser irradiation markedly increased the temperature and exerted significant toxicity through induction of apoptosis. In a mouse model of xenografts, tumors were identified by the strong fluorescence and photoacoustic signals. OPCN combined with NIR laser irradiation resulted in effective and complete thermal ablation of tumors without discernable side effects and tumor recurrence. We believe that OPCN hold tremendous translational potential for dual imaging-guided oxidative-photothermal combination anticancer therapy.

Three-dimensional (3D) printing (rapid prototyping or additive manufacturing) technologies have received significant attention in various fields over the past several decades. Tissue engineering applications of 3D bioprinting, in particular, have attracted the attention of many researchers. 3D scaffolds produced by the 3D bioprinting of biomaterials (bio-inks) enable the regeneration and restoration of various tissues and organs. These 3D bioprinting techniques are useful for fabricating scaffolds for biomedical and regenerative medicine and tissue engineering applications, permitting rapid manufacture with high-precision and control over size, porosity, and shape. In this review, we introduce a variety of tissue engineering applications to create bones, vascular, skin, cartilage, and neural structures using a variety of 3D bioprinting techniques.

Chitosan, a deacetylated chitin, is one of the few natural polymers similar to glycosaminoglycans (GAGs) widely distributed throughout connective tissues. It has been believed that the excellent biocompatibility of chitosan is largely attributed to this structural similarity. Chitosan is also known to possess biodegradability, antimicrobial activity and low toxicity and immunogenicity which are essential for scaffolds. In addition, the existence of free amine groups in its backbone chain enables further chemical modifications to create the additional biomedical functionality. For these reasons, chitosan has found a tremendous variety of biomedical applications in recent years. This chapter introduces the basic contents of chitosan and discusses its applications to artificial skin, artificial bone, and artificial cartilage in tissue engineering purpose.

Three-dimensional (3D) printing (rapid prototyping or additive manufacturing) technologies have received significant attention in various fields over the past several decades. Tissue engineering applications of 3D bioprinting, in particular, have attracted the attention of many researchers. 3D scaffolds produced by the 3D bioprinting of biomaterials (bio-inks) enable the regeneration and restoration of various tissues and organs. These 3D bioprinting techniques are useful for fabricating scaffolds for biomedical and regenerative medicine and tissue engineering applications, permitting rapid manufacture with high-precision and control over size, porosity, and shape. In this review, we introduce a variety of tissue engineering applications to create bones, vascular, skin, cartilage, and neural structures using a variety of 3D bioprinting techniques.