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Micropatterning of bioactive heparin-based hydrogels
Shah, Sunny Satish,Kim, Mihye,Cahill-Thompson, Katelyn,Tae, Giyoong,Revzin, Alexander Royal Society of Chemistry 2011 SOFT MATTER Vol.7 No.7
<P>This paper describes a UV photopatterning of bioactive heparin-based hydrogels on glass substrates. In this approach, hydrogel micropatterns were formed by UV-initiated thiol–ene reaction between thiolated heparin and diacrylated poly(ethylene) glycol (PEG-DA). Analysis of gelation kinetics showed that photo-crosslinked hydrogels formed faster and were stronger when compared to hydrogels formed by competing Michael addition reaction. To highlight bioactivity of heparin–PEG hybrid gels, hepatocyte growth factor (HGF) was mixed into prepolymer solution prior to hydrogel patterning. Immunostaining showed that HGF was retained after 5 days in the hybrid heparin–PEG hydrogel microstructures but was rapidly released from pure PEG gel microstructures. In a set of experiments further highlighting bioactivity of microfabricated heparin-based hydrogel, primary rat hepatocytes were cultured next to heparin and pure PEG hydrogel disks (∼500 µm in diameter). ELISA analysis revealed that hepatocytes residing next to heparin-based hydrogels were producing ∼4 times more albumin at day 7 compared to cells cultured next to inert PEG hydrogels. In the future, microfabricated heparin-based hydrogels described in this paper will be employed for designing cellular microenvironment <I>in vitro</I> and as vehicles for cell transplantation <I>in vivo</I>.</P> <P>Graphic Abstract</P><P>We describe micropatterning of heparin-based hydrogels and demonstrate that these hydrogel microstructures are bioactive; promoting function of cells cultured nearby. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c0sm00771d'> </P>
( Brunetto ),( Carla Coffin ),( Audrey Lau ),( Shuyuan Mo ),( John F. Flaherty ),( Anuj Gaggar ),( G Mani Subramanian ),( Mindie H. Nguyen ),( Selim Gurel ),( Alexander Thompson ),( Edward J. Gane ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: Suppression of the HBV in women of childbearing potential (WOCBP) has important implications in preventing transmission of HBV from mother to infant. Antiviral therapy that reduces HBV DNA to < 2x105 IU/mL at delivery in mothers can substantially reduce the risk of perinatal transmission. We evaluated the viral kinetics of TAF and TDF in WOCBP. Methods: : In two Phase 3 studies (HBeAg positive and negative patients), 1301 patients (37% female) were randomized (2:1) to receive TAF 25 mg QD or TDF 300 mg QD. All patients were required to have HBV DNA >2x104 IU/mL at screening and serum ALT >2 times AASLD criteria.WOCBP were defined as nonmenopausal females 18 years or older without history of hysterectomy, bilateral oophorectomy, or ovarian failure. For this subanalysis, patients were stratified by baseline HBV DNA levelsand the endpoints were virologic suppression to HBV DNA <29 IU/mL or < 2x105 IU/mL. Results: 365(76%) female were identified as WOCBP with 118 (32%) having HBV DNA >1x108 IU/mL at baseline. Suppression rates were generally similar between TAF and TDF groups and within viral load strata for HBeAg positive and negative patients. After 12 weeks of treatment with TAF or TDF, 77% of WOCBP with baseline HBV DNA <2x105 IU/mL had full suppression to <29 IU/mL compared to 1% of those at the highest baseline viral load (Figure A). By Week 24, 54% of all WOCBP had achieved complete viral suppression. Of WOCBP with baseline viral load ≥2x105 IU/mL (n=305), 76%, 89%, and 93% achieved viral load reduction to <2x105 IU/mL by Weeks 4, 8, and 12, respectively (Figure B). Conclusions: After 12 weeks of treatment the majority of WOCBP had HBV DNA to <2x105 IU/mL. In women with higher baseline viral loads, longer treatment duration may be necessary to achieve viral suppression below recommended thresholds.