Thermoresponsive phospholipid–poly(N-isopropylacrylamide) (PL-PNIPAM) conjugates were synthesized via reversible addition fragmentation chain transfer polymerization mediated by a phospholipid-modified trithiocarbonate. Temperature triggered the micellization of the PL-PNIPAM conjugate to form phosphate group-decorated micelles in the aqueous solution. Driven by the chelation of phospholipids and Ca2+, the PL-PNIPAM conjugate and Ca2+ ions formed size-tunable nanoclusters at a temperature beyond the lower critical solution temperature. To fabricate cross-linked nanogels, NIPAM was copolymerized with N-succinimidyl acrylate (NSA) to obtain the PL-P(NIPAM-co-NSA) conjugate bearing pendent cross-linkable functionalities. Subsequently, the size-controllable nanogels containing disulfide linkages were generated at 37 °C by cross-linking the PL-P(NIPAM-co-NSA)/Ca2+ nanoclusters with cystamine through modulation of Ca2+ concentrations. These negatively charged nanogels demonstrate temperature/pH/reduction triple responsiveness. The nanogels can be efficiently loaded with doxorubicin (DOX) and proteins with various isoelectric points. The DOX-loaded nanogels exhibited a temperature/pH/reduction triple-responsive release profile. The immobilized RNase A, BSA, and GOx retained the protein bioactivity. The release of RNase A-loaded nanogels possesses a temperature-responsive profile. The immobilization of Lys and cytochrome C in nanogels inhibited protein bioactivity. However, the addition of NaCl triggered the recovery of bioactivity. These multistimuli-responsive nanogels can provide a versatile platform applicable in biotechnology and drug/protein delivery.
Wenlin Chu,Xiang Ke,Zhiyun Dong,Jing Xie,Jun Luo,Jianshu Li
As an ideal biomaterial, the injectable dual crosslinking hydrogel can fill irregular shaped defects for treating bone defects. Despite advances in the fabrication of injectable dual crosslinking hydrogels, current methods pose several limitations in the gelation process, such as unadjustable injectability, materials loss after injection and the employment of nonphysiological environments. A more rational designed hydrogel should be shear-thinning and self-healing quickly after injection, which requires a reversible noncovalent or dynamic covalent interaction. Besides, the improved mechanical properties and stability can be achieved in vivo. In this present research study, inspired by a high Ca2+ concentration in the bone defect sites, a strategy combining hydrogen bonds and ion coordination to construct dual crosslinking hydrogels is developed. The prefabricated gel precursors based on hydrogen bonds of synthetic triblock poly(aspartic acid)–poly(ethylene glycol)–poly(aspartic acid) copolymers and tannic acid can be injected smoothly and recover rapidly to the initial state after injection. In addition, the hydrogel network can be crosslinked more tightly through the –COOH–Ca2+ chelation, which results in reinforced mechanical properties and stability. The developed injectable dual crosslinking hydrogels will provide a design idea for the secondary crosslinking of injectable hydrogels in vivo, especially in the bone repair sites.
Yang Liu,Guiliang Li,Qiu Han,Haibo Lin,Qiang Li,Jing Hua,Fu Liu
Inhibiting thrombosis in extracorporeal dialyzer is predominantly determined by the compatible interface design. It is challenging to develop anticoagulant dialyzers for clinical heparin free dialysis. Herein, we develop an environmentally friendly approach to construct a hydrogel skin composed of poly (sodium alginate-acrylic acid) P (SA-AA) network on polysulfone (PSf) membranes via pre-seeding initiator into membrane matrix and subsequently crosslinking SA and AA in aqueous solution. Physicochemical properties of modified membranes with different SA/AA ratio were characterized by attenuated total reflectance fourier transform infrared spectra (ATR-FTIR) spectrum, proton nuclear magnetic resonance ( 13 C NMR), scanning electron microscopy (SEM) and atomic force microscope (AFM) and contact angle. Antifouling property was demonstrated by proteins adsorption and E. coli adhesion. Hemocompatibility was comprehensively evaluated by hemolysis ratio, anticoagulation activity (APTT and TT), complement activation, platelets activation and contact activation. Anticoagulant dialyzer was fabricated via skin implantation strategy to implement a chronic renal swine dialysis with heparin free administration. Clotting was significantly inhibited during the whole dialysis session, moreover, the dialyzer showed improved toxins clearance, including urea (~185 mL/min), creatine (~153 mL/min), inorganic phosphorous (~120 mL/min) and β 2 -microglobulin (~110 mL/min). The modified membrane bearing abundant carboxylate groups contributes to excellent hydrophilicity and Ca 2+ chelation capability, which is considered to be the predominant anti-clotting mechanism via both intrinsic and extrinsic cascades. The anticoagulant PSf dialyzer demonstrates promising clinical application for heparin free dialysis.
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