Polysaccharide-Derived Ice Recrystallization Inhibitors with a Modular Design: The Case of Dextran-Based Graft Polymers.

Ice recrystallization inhibitors inspired from antifreeze proteins (AFPs) are receiving increasing interest for cryobiology and other extreme environment applications. Here, we present a modular strategy to develop polysaccharide-derived biomimetics, and detailed studies were performed in the case of dextran. Poly(vinyl alcohol) (PVA) which has been termed as one of the most potent biomimetics of AFPs was grafted onto dextran via thiol-ene click chemistry (Dex-g-PVA). This demonstrated that Dex-g-PVA is effective in IRI and its activity increases with the degree of polymerization (DP) (sizes of ice crystals were 18.846 ± 1.759 and 9.700 ± 1.920 µm with DPs of 30 and 80, respectively) and fraction of PVA. By means of the dynamic ice shaping (DIS) assay, Dex-g-PVA is found to engage on the ice crystal surfaces, thus the ice affinity accounts for their IRI activity. In addition, Dex- g-PVA displayed enhanced IRI activity compared to that of equivalent PVA alone. We speculate that the hydrophilic nature of dextran would derive PVA in a stretch conformation that favors ice binding. The modular design can not only offer polysaccharides IRI activity but also favor the ice-binding behavior of PVA.

A biocompatible cell cryoprotectant based on sulfoxide-containing amino acids: mechanism and application.

The preservation of cells at cryogenic temperatures requires the presence of cryoprotectants (CPAs). Dimethyl sulfoxide (DMSO), as a state-of-the-art CPA, is widely used for the storage of many types of cells. However, its intrinsic toxicity is still an obstacle for its applications in clinical practice. Herein, we report a DMSO analogue, L-methionine sulfoxide (Met(O)-OH), as a CPA for cell cryopreservation. The molecular-level cryopreservation roles of Met(O)-OH were investigated by experiments and molecular dynamics simulations. The results also found that Met(O)-OH showed high ice recrystallization inhibition (IRI) activity and the ice crystals in Met(O)-OH solution tend to be relatively round and smooth; moreover, the ice size was significantly reduced to 30.26 µm compared with pure water (135.87 µm) or DMSO solution (45.08 µm). At the molecular level, Met(O)-OH could stably bind the surface of the ice crystals and form more stable hydrogen bonds with ice compared with L-methionine. Moreover, Met(O)-OH could significantly reduce the damage to cells caused by osmotic shock and did not change the cell viability even at high concentration (4%). Based on these results, nucleated L929 cells and anuclear sheep red blood cells (SRBCs) were used as cell models to investigate the cryopreservation activity of Met(O)-OH. The results suggested that, under the optimum protocol, Met(O)-OH showed an effective post-thaw survival efficiency with ultrarapid freezing, and the post-thaw survival efficiency of L929 cells reached 84.0%. This work opens up the possibility for an alternative to traditional toxic CPA DMSO, and provides insights for the development of DMSO analogues with non-toxic/low toxicity for cell cryoprotection applications.

Injectable recombinant block polymer gel for sustained delivery of therapeutic protein in post traumatic osteoarthritis.

Protein-based biomaterials offer several advantages over synthetic materials, owing to their unique stimuli-responsive properties, biocompatibility and modular nature. Here, we demonstrate that E5C, a recombinant protein block polymer, consisting of five repeats of elastin like polypeptide (E) and a coiled-coil domain of cartilage oligomeric matrix protein (C), is capable of forming a porous networked gel at physiological temperature, making it an excellent candidate for injectable biomaterials. Combination of E5C with Atsttrin, a chondroprotective engineered derivative of anti-inflammatory growth factor progranulin, provides a unique biochemical and biomechanical environment to protect against post-traumatic osteoarthritis (PTOA) onset and progression. E5C gel was demonstrated to provide prolonged release of Atsttrin and inhibit chondrocyte catabolism while facilitating anabolic signaling in vitro. We also provide in vivo evidence that prophylactic and therapeutic application of Atsttrin-loaded E5C gels protected against PTOA onset and progression in a rabbit anterior cruciate ligament transection model. Collectively, we have developed a unique protein-based gel capable of minimally invasive, sustained delivery of prospective therapeutics, particularly the progranulin-derivative Atsttrin, for therapeutic application in OA.

Risk Factors for Cement Leakage and Adjacent Vertebral Fractures in Kyphoplasty for Osteoporotic Vertebral Fractures.

PURPOSE: Cement leakage and adjacent vertebral fractures are not uncommon after percutaneous augmentation. However, conclusive identification of risk factors for postprocedural complications remains elusive. The anticipation of leakage and successive fractures through the identification of risk factors will help physicians better inform patients of potential complications and establish procedural refinements key to risk reduction. The aim of this retrospective study was to summarize available reports of the risk factors for cement leak and adjacent vertebral fracture in or after kyphoplasty for osteoporotic vertebral compression fractures. METHODS: A total of 102 cases of bilateral percutaneous kyphoplasty (PKP), performed between January 2014 and December 2016, were retrospectively reviewed. Each case surveyed in this review included a minimum 1-year follow-up and data on age, sex, bone mineral density, Visual Analog Scale score, preoperative compression rate, kyphotic angle, treatment time, the volume of cement, and the intactness of the vertebral posterior wall (computed tomography scan) were collected. Pearson χ test and independent samples test were used to determine the relative risk factors of cement leak and adjacent vertebral fracture in patient subsets. RESULTS: Diabetic status and alteration in the Cobb angle after PKP exhibited a statistically significant correlation with the incidence of new adjacent vertebral fracture (group B) (P<0.05). In addition, the integrity of vertebral walls (P=0.001) and the volume of injected cement (P=0.026) significantly boosted the potential risk of cement leakage (P<0.05), although these variables did not associate with the adjacent fracture. Additional examined variables, including age, sex, Visual Analog Scale scores, number of fractures were not significantly associated with leakage or adjacent vertebral fracture risk. CONCLUSIONS: Diabetes and the alteration of the Cobb angle following PKP are factors positively related to the occurrence of postoperative adjacent vertebral fractures. It is also demonstrated that the integrity of vertebral walls and average volumes of injected cement are the possible risk factors of cement leakage while performing the PKP.

Production and characteristics of a bioflocculant by Klebsiella pneumoniae YZ-6 isolated from human saliva.

The production and characterization of a bioflocculant, MBF-6, by Klebsiella pneumoniae was investigated. Optimum culture conditions for bioflocculant production were an initial medium pH of 7, an incubation temperature of 30 °C, and an inoculum size of 1% (v/v) of cell density 1.0 × 10(8) cfu/mL. The carbon, nitrogen, and cation sources for optimum bioflocculant production were glucose, peptone, and ZnCl2. The bioflocculant mainly consisted of protein (3.4%) and sugar (95.1%). Fourier transform infrared (FTIR) spectrum revealed the presence of carboxyl and hydroxyl groups while the thermogravimetric analysis (TGA) showed a degradation temperature (T(d)) of 81.4 °C. MBF-6 had a good flocculating rate in kaolin suspension without cation addition and was stable over a wide range of pH and temperature. Investigation on the flocculation efficacy of the characterized MBF-6 for wastewater treatment of dairy, woolen, brewery, and sugar industries suggested it to be effective.