Design, Synthesis, and Biological Activities of Novel 2-Cyanoacrylate Compounds Containing Substituted Pyrazolyl or 1,2,3-Triazolyl Moiety.

To develop novel 2-cyanoacrylate derivatives with potential bioactivity, a number of 2-cyanoacrylate compounds, including substituted pyrazole or 1,2,3-triazole ring, were designed, prepared, and structurally detected by 1H NMR, 13C NMR, and elemental analysis. The biological assessment displayed that some designed compounds had significant herbicidal activities against Brassica juncea, Chenopodium serotinum, Rumex acetosa, Alopecurus aequalis, Polypogon fugax, and Poa annua at a dosage of 1500 g/ha. Furthermore, some derivatives still expressed satisfactory herbicidal activities against Brassica juncea, Chenopodium serotinum, and Rumex acetosa when the dosage was lowered to 150 g/ha, especially the inhibitory effects of compounds 9a, 9d, 9f, 9i, 10a, 10b, 10e, and 10n against Brassica juncea were all over 80%, compounds 9d, 9f, 9g, 9h, 9i, 10h, 10i, 10m, 10n, and 10o possessed more than 70% inhibition rates against Chenopodium serotinum, and compound 9d indicated 70% herbicidal activity against Rumex acetosa. These results provided an important basis for further design and discovery of biologically active 2-cyanoacrylate compounds.

Functional Nanoparticles Activate a Decellularized Liver Scaffold for Blood Detoxification.

Extracorporeal devices have great promise for cleansing the body of virulence factors that are caused by venomous injuries, bacterial infections, and biological weaponry. The clinically used extracorporeal devices, such as artificial liver-support systems that are mainly based on dialysis or electrostatic interaction, are limited to remove a target toxin. Here, a liver-mimetic device is shown that consists of decellularized liver scaffold (DLS) populated with polydiacetylene (PDA) nanoparticles. DLS has the gross shape and 3D architecture of a liver, and the PDA nanoparticles selectively capture and neutralize the pore-forming toxins (PFTs). This device can efficiently and target-orientedly remove PFTs in human blood ex vivo without changing blood components or activating complement factors, showing potential application in antidotal therapy. This work provides a proof-of-principle for blood detoxification by a nanoparticle-activated DLS, and can lead to the development of future medical devices for antidotal therapy.

Method for perfusion decellularization of porcine whole liver and kidney for use as a scaffold for clinical-scale bioengineering engrafts.

BACKGROUND: Whole-organ engineering provides a new alternative source of donor organs for xenotransplantation. Utilization of decellularized whole-organ scaffolds, which can be created by detergent perfusion, is a strategy for tissue engineering. In this article, our aim is to scale up the decellularization process to human-sized liver and kidney to generate a decellularized matrix with optimal and stable characteristics on a clinically relevant scale. METHODS: Whole porcine liver and kidney were decellularized by perfusion using different detergents (1% SDS, 1% Triton X-100, 1% peracetic acid (PAA), and 1% NaDOC) via the portal vein and renal artery of the liver and kidney, respectively. After rinsing with PBS to remove the detergents, the obtained liver and kidney extracellular matrix (ECM) were processed for histology, residual cellular content analysis, and ECM components evaluation to investigate decellularization efficiency, xenoantigens removal, and ECM preservation. RESULTS: The resulting liver and kidney scaffolds in the SDS-treated group showed the most efficient clearance of cellular components and xenoantigens, including DNA and protein, and preservation of the extracellular matrix composition. In comparison, cell debris was observed in the other decellularized groups that were generated using Triton X-100, PAA, and NaDOC. Special staining and immunochemistry of the porcine liver and kidney ECMs further confirmed the disrupted three-dimension ultrastructure of the ECM in the Triton X-100 and NaDOC groups. Additionally, Triton X-100 effectively eliminated the residual SDS in the SDS-treated group, which ensured the scaffolds were not cytotoxic to cells. Thus, we have developed an optimal method that can be scaled up for use with other solid whole organs. CONCLUSIONS: Our SDS-perfusion protocol can be used for porcine liver and kidney decellularization to obtain organ scaffolds cleared of cellular material, xenoimmunogens, and preserved vital ECM components.

[Anticoagulant Ability and Heparinization of Decellularized Biomaterial Scaffolds].

In order to enhance the anticoagulant properties of decellularized biological materials as scaffolds for tissue engineering research via heparinized process, the decellularized porcine liver scaffolds were respectively immobilized with heparin through layer-by-layer self-assembly technique (LBL), multi-point attachment (MPA) or end-point attachment (EPA). The effects of heparinization and anticoagulant ability were tested. The results showed that the three different scaffolds had different contents of heparin. All the three kinds of heparinized scaffolds gained better performance of anticoagulant than that of the control scaffold. The thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) of EPA scaffold group were longest in all the groups, and all the three times exceeded the measurement limit of the instrument. In addition, EPA scaffolds group showed the shortest prepared time, the slowest speed for heparin release and the longest recalcification time among all the groups. The decellularized biological materials for tissue engineering acquire the best effect of anticoagulant ability in vitro via EPA heparinized technique.

Biliary antibiotics irrigation for E. coli-induced chronic proliferative cholangitis and hepatolithiasis: A pathophysiological study in rabbits.

BACKGROUND: The gram-negative bacteria secreted endotoxin, Lipopolysaccharide (LPS), plays important roles in the formation and recurrence of hepatolithiasis and chronic biliary inflammation in patients of Southeast Asia. We aimed to elucidate the anti-inflammatory effect and mechanism of local antibiotics irrigation on chronic proliferative cholangitis (CPC) and hepatolithiasis. METHODS: Escherichia coli was injected into rabbit bile ducts to induce CPC. Rabbits were divided into sham operation (SO), povidone-iodine, Metronidazole plus chlorhexidine, ofloxacin, furacillin, Neosporin® G.U., and CPC groups. Local irrigation was performed for 28 days after CPC was established. Residual E. coli and LPS, and the expression of MCP-1, CD14, COX-2, VEGF, IL-6, NF-κB, TNF-α, Fas, TGF-ß1, α-SMA, Collagen-I, ß-glucuronidase, PKC, C-myc, and Mucin 5AC were assessed in bile duct tissues. RESULTS: The residual E. coli and LPS, and expression of MCP-1, CD14, COX-2, IL-6, NF-κB, TNF-α, Fas, TGF-ß1, α-SMA, ß-glucuronidase, PKC, C-myc, and Mucin 5AC in the SO, povidone-iodine, Metronidazole plus chlorhexidine, ofloxacin, and Neosporin® G.U. groups were significantly lower than those in the furacillin and CPC groups (P<0.05). VEGF and Collagen-I levels in the SO, povidone-iodine, metronidazole plus chlorhexidine, and ofloxacin groups were significantly lower than those in the furacillin, Neosporin® G.U., and CPC groups (P<0.05). CONCLUSIONS: LPS affects the pathophysiology of E. coli caused chronic proliferative cholangitis and hepatolithiasis recurrence. Local antibiotics irrigation could prevent chronic proliferative cholangitis and stones formation by decreasing LPS-induced proinflammatory and profibrotic cytokines release. Povidone iodine, metronidazole plus chlorhexidine, and ofloxacin were more effective than Neosporin® G.U. and furacillin.

Osteoinduction of calcium phosphate biomaterials in small animals.

Although osteoinduction mechanism of calcium phosphate (CP) ceramics is still unclear, several essential properties have been reported, such as chemical composition, pore size and porosity, etc. In this study, calcium phosphate powder (Ca3(PO4)2, CaP, group 1), biphasic calcium phosphate ceramic powder (BCP, group 2), and intact BCP rods (group 3) were implanted into leg muscles of mice and dorsal muscles of rabbits. One month and three months after implantation, samples were harvested for biological and histological analysis. New bone tissues were observed in 10/10 samples in group 1, 3/10 samples in group 2, and 9/10 samples in group 3 at 3rd month in mice, but not in rabbits. In vitro, human mesenchymal stem cells (hMSCs) were cultured with trace CaP and BCP powder, and osteogenic differentiation was observed at day 7. Our results suggested that chemical composition is the prerequisite in osteoinduction, and pore structure would contribute to more bone formation.

Grafted crystalline poly-perfluoroacrylate structures for superhydrophobic and oleophobic functional coatings.

This report describes the preparation of superhydrophobic and oleophobic surfaces by grafting of poly(perfluorodecylacrylate) chains with initiated chemical vapor deposition on silicon substrates. The grafting enhances the formation of a semicrystalline phase. The crystalline structures reduce the polymer chain mobility, resulting in nonwetting surfaces with both water and mineral oil. On the contrary, the same contacting liquid easily wets the amorphous ungrafted polymer.

Osteoinduction by Ca-P biomaterials implanted into the muscles of mice.

The osteoinduction of porous biphasic calcium phosphate ceramics (BCP) has been widely reported and documented, but little research has been performed on rodent animals, e.g., mice. In this study, we report osteoinduction in a mouse model. Thirty mice were divided into two groups. BCP materials (Sample A) and control ceramics (Sample B) were implanted into the leg muscle, respectively. Five mice in each group were killed at 15, 30, and 45 d after surgery. Sample A and Sample B were harvested and used for hematoxylin and eosin (HE) staining, immunohistochemistry (IHC) staining, and Alizarin Red S staining to check bone formation in the biomaterials. Histological analysis showed that no bone tissue was formed 15 d after implantation (0/5) in either of the two groups. Newly-formed bone tissues were observed in Sample A at 30 d (5/5) and 45 d (5/5) after implantation; the average amounts of newly-formed bone tissues were approximately 5.2% and 8.6%, respectively. However, we did not see any bone tissue in Sample B until 45 d after implantation. Bone-related molecular makers such as bone morphogenesis protein-2 (BMP-2), collagen type I, and osteopontin were detected by IHC staining in Sample A 30 d after implantation. In addition, the newly-formed bone was also confirmed by Alizarin Red S staining. Because this is the report of osteoinduction in the rodent animal on which all the biotechnologies were available, our results may contribute to further mechanism research.

A long-term evaluation of osteoinductive HA/beta-TCP ceramics in vivo: 4.5 years study in pigs.

It has been proved that some material-dependent calcium phosphate ceramics have intrinsic potentials to induce osteogenesis. But there is little literature concerning about the tissue response in long-term. The aim of this study is to evaluate the safety of the osteoinductive biocreamics and the stability of the newly formed bone after long-term tissue response. Porous calcium phosphate ceramics rods which contain hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP) were implanted in the dorsal muscles of Banna Minipig Inbreding Line. After 4.5 years, all the implanted rods with surrounding tissues were harvested and stained with hematoxylin and eosin for histological observation. The 7 months' rods were also harvested as short-term comparison. The histological results showed that compared with the short-term rods, amount of bone tissue formed after 4.5 years. And the newly formed bone in this bioceramics neither disappeared nor gave rise to uncontrolled growth. The bone growth in this bioceramics seemed to be self-confined. The surrounding soft tissues were normal and no tumor cell was found. We conclude that instead of disappearing or giving rise to out of control, the induced bone tissue trends to be further matured. And this bioceramics thus might have potentials in future clinical use.