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The correct folding of proteins is essential for appropriate cell function and is tightly regulated within the endoplasmic reticulum (ER). Environmental challenges and cellular conditions disrupt ER homeostasis and induce ER stress, which adversely affect protein folding and activate the unfolded protein response (UPR). It is now becoming recognized that cancer cells can overcome survival challenges posed within the tumor microenvironment by activating the UPR. Furthermore, the UPR has also been found to impose detrimental effects on immune cells by inducing immunoinhibitory activity in both tumor-infiltrating innate and adaptive immune cells. This suggests that these signaling axes may be important therapeutic targets, resulting in multifaceted approaches to eradicating tumor cells. In this mini-review, we discuss the role of the UPR in driving tumor progression and modulating the immune system’s ability to target cancer cells. Additionally, we highlight some of the key unanswered questions that may steer future UPR research.

Background: Scaffold-based gene therapy provides a promising approach for tissue engineering, which was important and popular as it combined medical applications and engineering materials’ knowledge. Objective: The decellularization techniques were employed to remove the cellular components from porcine elastic cartilages, leaving a native decellularized Extracellular Matrix (dECM) composition and architecture integrity of largely insoluble collagen, elastin, and tightly bound glycosaminoglycans. For newly designed collagen scaffold samples, elastic cartilages were hydrolyzed by protease with different concentrations to gain state completely and clearly. Methods: An extraction process of Supercritical Carbon Dioxide (ScCO2) was used to remove cellular components from porcine elastic cartilage. The dECM scaffolds with collagen must be characterized by Fourier transform infrared spectroscopy(FTIR), Thermo-Gravimetric Analysis (TGA), and Scanning Electron Microscope (SEM). Results: The study provided a new treatment combined with supercritical carbon dioxide and alkaline/ protease to prepare dECM scaffolds with hole-scaffold microstructures and introduce into a potential application on osteochondral tissue engineering using scaffold-based gene therapy. The new process is simple and efficient. The pore-scaffold microstructures were observed in dECM scaffolds derived from porcine elastic cartilages. The Tdmax values of the resulting dECM scaffolds were observed at over 330oC. Conclusion: A series of new scaffolds were successfully obtained from porcine tissue by using ScCO2 and alkaline/enzyme treatments such as a mixing aqueous solution of NH4OH and papain. The dECM scaffolds with high thermal stability were obtained. The resulting scaffold with clean pore-scaffold microstructure could be a potential application for scaffold-based gene therapy.

Chronic inflammation triggers compensatory immunosuppression to stop inflammation and minimize tissue damage. Studies have demonstrated that endoplasmic reticulum (ER) stress augments the suppressive phenotypes of immune cells; however, the molecular mechanisms underpinning this process and how it links to the metabolic reprogramming of immunosuppressive macrophages remain elusive. In the present study, we report that the helper T cell 2 cytokine interleukin-4 and the tumor microenvironment increase the activity of a protein kinase RNA-like ER kinase (PERK)-signaling cascade in macrophages and promote immunosuppressive M2 activation and proliferation. Loss of PERK signaling impeded mitochondrial respiration and lipid oxidation critical for M2 macrophages. PERK activation mediated the upregulation of phosphoserine aminotransferase 1 (PSAT1) and serine biosynthesis via the downstream transcription factor ATF-4. Increased serine biosynthesis resulted in enhanced mitochondrial function and α-ketoglutarate production required for JMJD3-dependent epigenetic modification. Inhibition of PERK suppressed macrophage immunosuppressive activity and could enhance the efficacy of immune checkpoint programmed cell death protein 1 inhibition in melanoma. Our findings delineate a previously undescribed connection between PERK signaling and PSAT1-mediated serine metabolism critical for promoting immunosuppressive function in M2 macrophages.

Continuous work and developments in biomedical materials used in three-dimensional (3D) bioprinting have contributed to significant growth of 3D bioprinting applications in the production of personalized tissue-repairing membrane, skin graft, prostheses, medication delivery system, and 3D tissue engineering and regenerative medicine scaffolds. The design of clinic products and devices focus on new natural and synthetic biomedical materials employed for therapeutic applications in different 3D bioprinting technologies. Design and characterization of natural and synthetic soft polymeric materials with biomimetic 3D microarchitecture were considered. The natural soft polymeric materials would focus on new design bioinspired membranes containing supercritical fluids-decellularized dermal scaffolds for 3D bioprinting potential applications. Synthetic soft polymeric materials would focus on bioinspired polyvinyl alcohol (b-PVA) matrix with structural foam-wall microarchitectures. Characterization, thermal stability, and cell morphology of the b-PVA and the corresponding collagen-modified b-PVA were employed to evaluate their potential tissue engineering applications. Also, the b-PVA materials were conductive to HepG2 cells proliferation, migration, and expression, which might serve as a promising liver cell culture carrier to be used in the biological artificial liver reactor. TGA, DTG, DSC, SEM, and FTIR were employed to build up the effective system identification approach for biomimetic structure, stability, purity, and safety of target soft matrix.

Tumor-infiltrating monocytes can mature into Macrophages that support tumor survival or that display antitumor properties. To explore mechanisms steering Macrophage maturation, we assessed the effects of supernatants from squamous cell carcinoma cell lines (FaDu and SCC) on monocyte-derived Macrophage maturation. Purified monocytes were incubated in medium or medium supplemented with supernatants from FaDu and SCC9 or the leukemia monocytic cell line, THP-1. Macrophages were examined for markers of maturation (CD14, CD68), activation (HLA-DR, CD86, IL15R), scavenger receptor (CD36), toll-like receptor (TLR4), M2 marker (CD206), immune checkpoint (PD-L1), and intracellular chemokine expression (IP-10). Compared to other conditions, cells incubated with FaDu or SCC9 supernatants displayed enhanced survival, down-regulation of cell surface HLA-DR, CD86, IL-15R, CD36, and intracellular IP-10 expression, and increased cell surface PD-L1, CD14, and CD206 expression. Despite expressing TLR4 and CD14, Macrophages matured in tumor supernatants failed to respond to stimulation with the canonical TLR4 agonist, LPS. These changes were accompanied by a decrease in intracellular phospho-p38 expression in tumor supernatant conditioned Macrophages. Depletion of fatty acids from tumor supernatants or treatment of cell cultures with an inhibitor of fatty acid oxidation, Etomoxir, reversed a number of these phenotypic changes induced by tumor supernatants. Additionally, Macrophages incubated with either palmitic acid or oleic acid developed similar phenotypes as cells incubated in tumor supernatants. Together, these data suggest that fatty acids derived from tumor cells can mediate the maturation of Macrophages into a cell type with limited pro-inflammatory characteristics.

In the present study, supercritical fluid was employed to prepare a kind of supercritical fluids-decellularized dermal-based scaffold (SFDDS) from porcine dermal tissue. Further, new composite bioscaffolds containing SFDDS were designed for bioprinting applications. Then, the effect of crosslinking functionality on microstructures and thermal properties of the composite bioscaffolds containing decellularized extracellular matrix were studied. The results of thermal stability from thermogravimetric analysis and difference thermogravimetry demonstrated the structural stability of the composite bioscaffolds. A method was designed to prepare bioinspired decellularized dermal-based composite bioscaffolds, which were further characterized by infrared spectroscopy, scanning electron microscopy, and thermogravimetry analysis.

Lung macrophages are substantially distinct from other tissue-resident macrophages. They act as frontier sentinels of the alveolar-blood interface and are constantly exposed to various pathogens. Additionally, they precisely regulate immune responses under homeostatic and pathological conditions to curtail tissue damage while containing respiratory infections. As a highly heterogeneous population, the phenotypes and functions of lung macrophages with differing developmental ontogenies are linked to both intrinsic and extrinsic metabolic processes. Importantly, targeting these metabolic pathways greatly impacts macrophage functions, which in turn leads to different disease outcomes in the lung. In this review, we will discuss underlying metabolic regulation of lung macrophage subsets and how metabolic circuits, together with epigenetic modifications, dictate lung macrophage function during bacterial infection.

Metabolites are the essential substrates for epigenetic modification enzymes to write or erase the epigenetic blueprint in cells. Hence, the availability of nutrients and activity of metabolic pathways strongly influence the enzymatic function. Recent studies have shed light on the choreography between metabolome and epigenome in the control of immune cell differentiation and function, with a major focus on histone modifications. Yet, despite its importance in gene regulation, DNA methylation and its relationship with metabolism is relatively unclear. In this review, we will describe how the metabolic flux can influence epigenetic networks in innate and adaptive immune cells, with a focus on the DNA methylation cycle and the metabolites S‐adenosylmethionine and α‐ketoglutarate. Future directions will be discussed for this rapidly emerging field.

C-type lectin domain family 4, member a4 (Clec4a4) is a C-type lectin inhibitory receptor specific for glycans thought to be exclusively expressed on murine CD8α− conventional dendritic cells. Using newly generated Clec4a4-mCherry knock-in mice, we identify a subset of Clec4a4-expressing eosinophils uniquely localized in the small intestine lamina propria. Clec4a4+ eosinophils evinced an immunomodulatory signature, whereas Clec4a4− eosinophils manifested a proinflammatory profile. Clec4a4+ eosinophils expressed high levels of aryl hydrocarbon receptor (Ahr), which drove the expression of Clec4a4 as well as other immunomodulatory features, such as PD-L1. The abundance of Clec4a4+ eosinophils was dependent on dietary AHR ligands, increased with aging, and declined in inflammatory conditions. Mice lacking AHR in eosinophils expanded innate lymphoid cells of type 2 and cleared Nippostrongylus brasiliensis infection more effectively than did wild-type mice. These results highlight the heterogeneity of eosinophils in response to tissue cues and identify a unique AHR-dependent subset of eosinophils in the small intestine with an immunomodulatory profile.

Tumor cells undergo rapid aerobic glycolysis to fuel growth and proliferation. A recent finding in Nature reveals that tumor-infiltrating myeloid cells demonstrate greater capacity for glucose uptake than tumor cells and consume significant amounts within the tumor milieu. Unexpectedly, tumor cells account for the highest glutamine utilization in the tumor microenvironment.

A method for quantifying the bovine collagen type V (Col. V) was established based on high-performance liquid chromatography coupled to mass spectrometry by the marker peptide external standard. High-purity Col. V was extracted by the acid-enzyme hydrolysis process, and the marker peptide of Col. V was identified by LCQ mass spectrometry as GPAGPMGLTGR. A broad linear range (0.01-5.00 μg/mL) with a correlation coefficient of 0.9984 was achieved, and the limit of detection and limit of quantification were found to be 3.00 × 10

Collagen Type V (Col. V) plays an essential role in cell behaviors and has attracted increasing attention in recent years. High-purity Col. V is needed for evaluating its biological properties. In this research, the enzymatic hydrolysis process was combined with ultrafiltration to purify Col. V from the bovine cornea. The purity of Col. V was determined to be above 90% by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and high-performance liquid chromatography methods. The effect of Col. V on cell behaviors was evaluated. The circular dichroism spectroscopy results demonstrated that the extracted Col. V exhibited a complete triple helix structure. SDS-PAGE suggested that the molecular weight of Col. V was 440 kDa. The self-assembly experiment revealed that the proportion of Col. V in the collagen mixture can affect the Col. I fiber diameter. The cell culture results implied that Col. V can inhibit fibroblasts (L929) proliferation. The L929 showed maximum mobility when the addition of Col. V was 30%. Thus, Col. V has the effect of inhibiting L929 proliferation and promoting migration. The high-purity Col. V provides useful information for further understanding its biological implications.

Traditional drainage materials used in a surgical treatment or in wound management are not good enough in both the effectiveness and efficiency because they may cause infection due to their characteristics. Therefore, a novel drainage material should be essential and designed to solve the problem. Avian skeleton and feather rachises may be good reference objects to mimic in designing a novel drainage material because its good cell structure which support a bird to fly safe and efficient. The term “nature-Bioinspired” is associated with a sequence of efforts to understand, synthesize and imitate any natural object or phenomenon either in a tangible or intangible form, which allows us to obtain improved insights into nature. Such inspirations can come through materials, processes, or designs. In this study, a new medical matrix derived from polyvinyl alcohol foam with air cavities inspired by avian skeleton and feather rachises for drainage medical treatments was designed, prepared, and characterized. Establishment of biomimetic biomedical inventive principles and a bio-inspired design-thinking method for innovative design of biomimetic medical devices and biomaterials were achieved. Also, the medical device (MD) unified problem-driven bioinspired evaluating approach was established to guide biomimetic design of biomaterials and the corresponding medical devices for various clinic applications.

Nano-bioscaffolds obtained from decellularized tissues have been employed in several medical applications. Nano-bioscaffolds could provide structural support for cell attachment and a suitable environment with sufficient porosity for cell growth and proliferation. In this study, a new combined method constitutes a decellularization protocol to remove the tissue and cellular molecules from porcine dermis for preparation of nano-bioscaffolds with fibrous extracellular matrix via pre- and post-treatment of supercritical fluids. The supercritical fluids-assisted nano-bioscaffolds were characterized by peptide identification, infrared spectrum of absorption, morphology, histological observations, DNA quantification, and hemocompatibility. Further, the resulting nano-bioscaffolds could be employed to obtain new cross-linked composite nano-bioscaffold containing collagen and acellular matrix.

Osteoarthritis (OA) is a chronic disease caused by the damage of articular cartilage. Kartogenin (KGN) is a well-recognized small molecule which could induce MSCs chondrogenesis and promote cartilage repair treatments. Nano-level micells could be a suitable drug carrier technology for the treatments. In this study, the acid-responsive methoxy poly(ethylene oxide)-hydrazone-poly(ε-caprolactone) copolymers, mPEG-Hz

Tumor-associated macrophages (TAMs) display pro-tumorigenic phenotypes for supporting tumor progression in response to microenvironmental cues imposed by tumor and stromal cells. However, the underlying mechanisms by which tumor cells instruct TAM behavior remain elusive. Here, we uncover that tumor-cell-derived glucosylceramide stimulated unconventional endoplasmic reticulum (ER) stress responses by inducing reshuffling of lipid composition and saturation on the ER membrane in macrophages, which induced IRE1-mediated spliced XBP1 production and STAT3 activation. The cooperation of spliced XBP1 and STAT3 reinforced the pro-tumorigenic phenotype and expression of immunosuppressive genes. Ablation of XBP1 expression with genetic manipulation or ameliorating ER stress responses by facilitating LPCAT3-mediated incorporation of unsaturated lipids to the phosphatidylcholine hampered pro-tumorigenic phenotype and survival in TAMs. Together, we uncover the unexpected roles of tumor-cell-produced lipids that simultaneously orchestrate macrophage polarization and survival in tumors via induction of ER stress responses and reveal therapeutic targets for sustaining host antitumor immunity. Tumor-associated macrophages support an immunosuppressive tumor microenvironment. Di Conza et al. uncover how IRE1–XBP1 and IRE1−STAT3 endoplasmic reticulum stress responses pathways are engaged by tumor-derived lipids to orchestrate pro-tumorigenic features and survival in tumor-associated macrophages.

BACKGROUND: The biologic scaffolds derived from decellularized tissues and organs have been successfully developed in a variety of preclinical and/or clinical studies. OBJECTIVE: The new decellularized liver-regenerative 3D printing biomaterials were designed and prepared for cell-based liver therapies. METHODS: An extraction process was employed to remove the tissue and cellular molecules from porcine liver via pretreatment of supercritical fluid of carbon dioxide (ScCO2). Varying porosities of the decellularized liver tissues were created using papain-containing reagent treatments after ScCO2. RESULTS: The resulting liver-regenerative 3D printing biomaterials of decellularized liver collagen scaffolds were characterized by Fourier transform infrared spectroscopy, thermo-gravimetric analysis, differential scanning calorimetry and scanning electron microscopy. CONCLUSIONS: The decellularized liver collagen scaffolds with good thermal stability (>150 °C) were obtained and employed as liver-regenerative 3D printing biomaterials for cell-based liver therapies.

Alginate-based composite scaffold membranes with various ratios of decellularized extracellular matrices could be designed and obtained from porcine skin tissue by using supercritical carbon dioxide fluid technology. Retention of decellularized extracellular matrix (dECM) and scaffold-structure integrity was observed. This work provides a simple and time-saving process for the preparation of biomedical alginate-based composite scaffold membranes with fibrous dECM micro-scaffolds, which were further characterized by Fourier transform infrared spectroscopy (FTIR), thermo-gravimetric analysis (TGA), and scanning electron microscope (SEM). The introduction of fibrous dECM micro-scaffolds enhanced the thermal stability and provided expected effects on the biological properties of the designed composite scaffold membranes in regenerative applications.

ILC3s are innate immune cells in the intestine that contribute to mucosal barrier integrity and support antimicrobial responses. Di Luccia et al. show that an mTORC1-HIF1α–mediated metabolic program sustains ILC3 numbers and activation in both mouse and human., Group 3 innate lymphoid cells (ILC3s) are the innate counterparts of Th17 that require the transcription factor RORγt for development and contribute to the defense against pathogens through IL-22 and IL-17 secretion. Proliferation and effector functions of Th17 require a specific mTOR-dependent metabolic program that utilizes high-rate glycolysis, while mitochondrial lipid oxidation and production of reactive oxygen species (mROS) support alternative T reg cell differentiation. Whether ILC3s employ a specific metabolic program is not known. Here, we find that ILC3s rely on mTOR complex 1 (mTORC1) for proliferation and production of IL-22 and IL-17A after in vitro activation and Citrobacter rodentium infection. mTORC1 induces activation of HIF1α, which reprograms ILC3 metabolism toward glycolysis and sustained expression of RORγt. However, in contrast to Th17, ILC3 activation requires mROS production; rather than inducing an alternative regulatory fate as it does in CD4 T cells, mROS stabilizes HIF1α and RORγt in ILC3s and thereby promotes their activation. We conclude that ILC3 activation relies on a metabolic program that integrates glycolysis with mROS production., Graphical Abstract

Most tissue-resident macrophage populations develop during embryogenesis, self-renew in the steady state and expand during type 2 immunity. Whether shared mechanisms regulate the proliferation of macrophages in homeostasis and disease is unclear. Here we found that the transcription factor Bhlhe40 was required in a cell-intrinsic manner for the self-renewal and maintenance of large peritoneal macrophages (LPMs), but not that of other tissue-resident macrophages. Bhlhe40 was necessary for the proliferation, but not the polarization, of LPMs in response to the cytokine IL-4. During infection with the helminth Heligmosomoides polygyrus bakeri, Bhlhe40 was required for cell cycling of LPMs. Bhlhe40 repressed the expression of genes encoding the transcription factors c-Maf and Mafb and directly promoted expression of transcripts encoding cell cycle-related proteins to enable the proliferation of LPMs. In LPMs, Bhlhe40 bound to genomic sites co-bound by the macrophage lineage-determining factor PU.1 and to unique sites, including Maf and loci encoding cell-cycle-related proteins. Our findings demonstrate a tissue-specific control mechanism that regulates the proliferation of resident macrophages in homeostasis and type 2 immunity. Edelson and colleagues show that the transcription factor Bhlhe40 is required in a cell-intrinsic manner for the self-renewal and maintenance of large peritoneal macrophages, but not that of other tissue-resident macrophages.

Curcumin is a natural active constituent with a great variety of beneficial biological and pharmacological activities, is a practically water-insoluble component. The scope of the present work was to prepare a solid dispersion (SD) formulation to enhance the dissolution rate of curcumin. The SD was prepared using curcumin and β-cyclodextrin (CD)/HA via a classical ethanol-based solvent evaporation method. The as-prepared β-CD/HA and SDs were selectively characterised by various analytical techniques including X-ray diffraction, transmission electron microscopy, scanning electron microscopy, specific surface area/pore size analysis, Fourier transform infrared spectroscopy, and high-performance liquid chromatography. According to the dissolution tests, it was confirmed that β-CD/HA–curcumin SD can significantly enhance the dissolution of curcumin. In addition, an increasing trend was seen between the β-CD weight ratio and the dissolution rate of curcumin, and β-CD/HA–curcumin (9:1) SD was shown to be the best formulation among all tested samples with over 90% curcumin dissolved in 180 min. Besides, β-CD/HA–curcumin (9:1) SD exhibited pH and medium-dependent curcumin release behaviours. The antioxidant activity of released curcumin showed no difference to original curcumin. These results clearly demonstrated β-CD/HA can be a promising SD carrier to improve the dissolution of curcumin.

Tissue-engineering was important which combine medical applications and engineering materials. An extraction process was employed to remove the tissue and cellular molecules from porcine skin in this study via pretreatment of supercritical fluid a designed combined procedure of supercritical fluids of carbon dioxide and protease treatments at low temperatures. Varying porosities of the decellularized tissues were then created using protease reagent treatments. The author studied characterizations of the designed decellularized scaffolds derived from porcine skins via supercritical fluid and protease reagent treatments.

Tissue-engineering was important and popular which combine medical applications and engineering materials knowledge, just like decellularization techniques were employed to remove the cellular components from porcine elastic cartilages, leaving a native decellularized extracellular matrix(dECM) composition and architecture integrity of largely insoluble collagen, elastin, and tightly bound glycosaminoglycans. Particularly, an extraction process of supercritical carbon dioxide(ScCO2) was used to remove cellular components from porcine skins. The porcine skins must remove lipids and other impurities by using ScCO2 procedure. In this study, a series of new composite membranes with decellularized scaffolds could be designed and obtained from porcine skin tissue by using supercritical carbon dioxide fluid technology. The retain decellularized extracellular matrix (dECM) and integrity scaffold-structure could be observed in the new composite membranes. This work provides a simple and time-saving method process for preparation of biomedical composite membranes with dECM scaffolds for biomimetic bioinks, which were further characterized by Fourier transform infrared spectroscopy (FTIR), thermo-gravimetric analysis (TGA), and scanning electron microscope(SEM).

A gelatin-based hydrogel scaffold with highly uniform pore size and biocompatibility was fabricated for cartilage tissue engineering using microfluidic 3D-foaming technology. Mainly, bubbles with different diameters, such as 100 μm and 160 μm, were produced by introducing an optimized nitrogen gas and gelatin solution at an optimized flow rate, and N2/gelatin bubbles were formed. Furthermore, a cross-linking agent (1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide, EDC) was employed for the cross-linking reaction of the gelatin-based hydrogel scaffold with uniform bubbles, and then the interface between the close cells were broken by degassing. The pore uniformity of the gelatin-based hydrogel scaffolds was confirmed by use of a bright field microscope, conjugate focus microscope and scanning electron microscope. The in vitro degradation rate, mechanical properties, and swelling rate of gelatin-based hydrogel scaffolds with highly uniform pore size were studied. Rabbit knee cartilage was cultured, and its extracellular matrix content was analyzed. Histological analysis and immunofluorescence staining were employed to confirm the activity of the rabbit knee chondrocytes. The chondrocytes were seeded into the resulting 3D porous gelatin-based hydrogel scaffolds. The growth conditions of the chondrocyte culture on the resulting 3D porous gelatin-based hydrogel scaffolds were evaluated by MTT analysis, live/dead cell activity analysis, and extracellular matrix content analysis. Additionally, a dynamic culture of cartilage tissue was performed, and the expression of cartilage-specific proteins within the culture time was studied by immunofluorescence staining analysis. The gelatin-based hydrogel scaffold encouraged chondrocyte proliferation, promoting the expression of collagen type II, aggrecan, and sox9 while retaining the structural stability and durability of the cartilage after dynamic compression and promoting cartilage repair.

For patients with extensive full-thickness burns who do not have sufficient autologous split-thickness skin for skin grafts, the application of biological skin substitutes may be considered. The aim of this study was to find an optimal new type method for the production of a biovital skin substitute based on acellular dermal matrix (ADM) and preclinical evaluations. In this work, 25 methods of ADM production were assessed. The proposed methods are based on the use of the following enzymes: papain, Carica papaya lipase (CPL), and purification using a polymer/salt aqueous two-phase system. The obtained ADM samples were characterized via scanning electron microscopy (SEM), porosity measurement and water vapor transmission test. Results showed that the collagen bundles of ADM microparticles were intact and orderly. Through differential scanning calorimetry (DSC), thermo gravimetric analysis (TGA) and biocompatibility tests, the results indicated that the proportion of papain and CPL was the same and 5 h processing time are the optimum conditions for ADM preparation and the material showed good biocompatibility. Our results suggested that the potential of developing this kind of decellularization process to manufacture ADM scaffolds for clinical application.

A new biomaterial containing polyvinyl alcohol foam with a fully open-cell microstructure would be designed and prepared via air-foaming procedure in this study. The resulting biomaterials might provide several functional properties for various clinic potential applications. Also, the resulting biomaterial containing polyvinyl alcohol foam could be employed to prepare a series of new medical device for the clinic potential applications. Further, a systematic design-thinking method for innovative design of medical device would be built up and provided. A series of new medical devices would be designed and obtained.

Scaffold-based gene therapy provides a promising approach for tissue engineering, which was important and popular as it combined medical applications and engineering materials' knowledge.The decellularization techniques were employed to remove the cellular components from porcine elastic cartilages, leaving a native decellularized Extracellular Matrix (dECM) composition and architecture integrity of largely insoluble collagen, elastin, and tightly bound glycosaminoglycans. For newly designed collagen scaffold samples, elastic cartilages were hydrolyzed by protease with different concentrations to gain state completely and clearly.An extraction process of Supercritical Carbon Dioxide (ScCO2) was used to remove cellular components from porcine elastic cartilage. The dECM scaffolds with collagen must be characterized by Fourier transform infrared spectroscopy(FTIR), Thermo-Gravimetric Analysis (TGA), and Scanning Electron Microscope (SEM).The study provided a new treatment combined with supercritical carbon dioxide and alkaline/ protease to prepare dECM scaffolds with hole-scaffold microstructures and introduce into a potential application on osteochondral tissue engineering using scaffold-based gene therapy. The new process is simple and efficient. The pore-scaffold microstructures were observed in dECM scaffolds derived from porcine elastic cartilages. The TA series of new scaffolds were successfully obtained from porcine tissue by using ScCO

This study was aimed to develop the new transdermal formulation to improve the permeability of buprenorphine. The apparent partition coefficients of buprenorphine were measured using the buffers at pH 1.2 to 10.0 as aqueous phase. The solubility of buprenorphine was 12.97 μg/mL in the 0.1 M phosphate buffer at pH 6.8. The influences of vehicles at different pH, adhesives, and permeation enhancers on the penetration of buprenorphine through nude mouse skin were investigated using the static Franz diffusion cells. The permeation parameter J(subscript ss) of buprenorphine increased along with the reduction of the pH of receptor fluid, and the vehicle at pH 6.8 was used in the following skin permeation studies. The pressure sensitive adhesives (PSA) including polyisobutylene (PIB), polystyrene-block-polyisoprene-block-polystyrene (SIS), and acrylic adhesives were evaluated. The permeability of buprenorphine was higher in the PIB or SIS adhesives than that in the acrylic adhesives under the condition without enhancer. When combined the enhancers with propylene glycol (PG) to improve the penetration of buprenorphine, the permeation-enhancing effects of enhancers were in the following order: lauric acid ＞ linolenic acid ＞ menthol ＞ oleic acid ＞ N-methyl-2-pyrrolidone (NMP) ＞ laurocapram ＞ glabridin. Finally, a matrix-type transdermal delivery system for buprenorphine was formulated using acrylic adhesive, PG, and lauric acid. The Jss parameter was 2.68±0.20 μg/cm^2/h and buprenorphine permeated across the nude mouse skin was 31.68%.

The design of medical devices could be applied and developed for new treatment procedures instead of the traditional therapy procedures...

Traditional medical soft matrix used in a surgical treatment or in wound management was not good enough in both the structural support and interconnectivity to be applied in tissue engineering as a scaffold. Avian skeleton and feather rachises might be good reference objects to mimic in designing a scaffold material with good structural support and high interconnectivity because of its structural foam-wall microarchitectures and structural pneumaticity. In this study, a biomimetic airstream pore-foaming process was built up and the corresponding new medical soft matrix derived from polyvinyl alcohol matrix (PVAM) with air cavities inspired by avian skeleton and feather rachises was prepared. Furthermore, the resulting medical soft matrix and bovine Achilles tendon type I collagen could be employed to prepare a new collagen-containing composite matrix. Characterization, thermal stability and cell morphology of the bioinspired PVA matrix and the corresponding collagen-modified PVA composite matrix with open-cell foam-wall microarchitectures were studied for evaluation of potential tissue engineering applications. TGA, DTG, DSC, SEM and FTIR results of new bioinspired PVA matrix were employed to build up the effective system identification approach for biomimetic structure, stability, purity, and safety of target soft matrix. The bioinspired PVA matrix and the corresponding collagen-modified PVA composite matrix would be conductive to human hepatoblastoma HepG2 cell proliferation, migration, and expression which might serve as a promising liver cell culture carrier to be used in the biological artificial liver reactor.

This study presents a designed alginate-based polymeric composite foam material containing decellularized elastic cartilage microscaffolds from porcine elastic cartilage by using supercritical fluid and papain treatment for medical scaffold biomaterials. The microstructure and thermal property of the designed alginate-based polymeric composite foam materials with various controlled ratios of alginate molecules and decellularized elastic cartilage microscaffolds were studied and characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and differential thermal gravimetric analysis (TGA/DTG). The microstructure and thermal property of the composite foam materials were affected by the introduction of decellularized elastic cartilage microscaffolds. The designed alginate-based polymeric composite foam materials containing decellularized elastic cartilage microscaffolds were ionically cross-linked with calcium ions by soaking the polymeric composite foam materials in a solution of calcium chloride. Additional calcium ions further improved the microstructure and thermal stability of the resulting ionic cross-linked alginate-based polymeric composite foam materials. Furthermore, the effect of crosslinking functionality on microstructures and thermal properties of the resulting polymeric composite foam materials were studied to build up useful information for 3D substrates for cultivating and growing cartilage cells and/or cartilage tissue engineering.

Tissue-engineering was important which combine medical applications and engineering materials. A extraction process was employed to remove the tissue and cellular molecules from porcine costal cartilages in this study via pretreatment of supercritical fluid of carbon dioxide. Varying porosities of the decellularized tissues were then created using papain-containing reagent treatments. The author studied characterizations of the designed decellularized scaffolds derived from porcine costal cartilages via supercritical fluid and papain-containing reagent treatments.

The transcription factor BHLHE40 is an emerging regulator of the immune system. Recent studies suggest that BHLHE40 regulates type 2 immunity, but this has not been demonstrated in vivo. We found that BHLHE40 is required in T cells for a protective T(H)2 cell response in mice infected with the helminth Heligmosomoides polygyrus bakeri (H. polygyrus). H. polygyrus elicited changes in gene and cytokine expression by lamina propria CD4(+) T cells, many of which were BHLHE40-dependent, including production of the common beta (β(C), CSF2RB) chain family cytokines GM-CSF and IL-5. In contrast to deficiency in GM-CSF or IL-5 alone, loss of both GM-CSF and IL-5 signaling impaired protection against H. polygyrus. Overall, we show that BHLHE40 regulates the T(H)2 cell transcriptional program during helminth infection to support normal expression of Csf2, Il5, and other genes required for protection and reveal unexpected redundancy of β(C) chain-dependent cytokines previously thought to possess substantially divergent functions.

The cytokines GM-CSF and IL-5 are thought to possess largely divergent functions despite a shared dependence on the common beta (βC) chain to initiate signaling. Although IL-5 is part of the core type 2 cytokine signature and is required for protection against some helminths, it is dispensable for immunity to others, such asHeligmosomoides polygyrus bakeri(H. polygyrus). Whether this is due to compensatory mechanisms is unclear. The transcription factor Bhlhe40 has been shown to control GM-CSF production and is proposed to be a novel regulator of T helper type 2 cells. We have found that Bhlhe40 is required in T cells for a protective memory response to secondaryH. polygyrusinfection.H. polygyrusrechallenge elicited dramatic Bhlhe40-dependent changes in gene and cytokine expression by lamina propria CD4+T cells andin vitro-polarized TH2 cells, including induction of GM-CSF and maximal production of type 2 cytokines including IL-5. βCchain-deficient, but not GM-CSF-deficient, mice rechallenged withH. polygyrushad severely impaired protective immunity. Our results demonstrate that Bhlhe40 is an essential regulator of TH2 cell immunity during helminth infection and reveal unexpected redundancy of βCchain-dependent cytokines.