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  • Injectable Click Chemistry-based Bioadhesives for Accelerated Wound Closure
    Injectable Click Chemistry-based Bioadhesives for Accelerated Wound Closure July 30,2020.
    Tissue adhesives play a vital role in surgical processes as a substitute for sutures in wound closure. Tissue adhesives, have been widely used in dentistry , orthopedics , and cardiovascular wounds closure to partially replace the traditional suturing approaches that often induce tissue deformation, irregular blood flow, and wound dehiscence. However, many of the existing commercial tissue adhesives have flaws that become evident upon application. For example, cyanoacrylate (Super Glue), which is considered as the strongest tissue adhesive,  has been shown to possess strong cytotoxicity . Fibrin glueand polyethylene glycol adhesivesare widely used due to their fast closure and biodegradability .  However, both types of glue have limited applications due to their poor tissue-adhesive property and tensile strength. This study present click chemistry enhanced, dual-crosslinked CS bioadhesive as a new strategy for wound closure with strong adhesive strength, injectability, and biocompatibility. In detail, CS-TCO and CS-Tz precursors were synthesized through carboxyl-to-amine crosslinking (Scheme 1). Upon administration, 4-arm PEG-PALD was mixed with one of the precursors and both of the precursors were injected and mixed within the wound (Scheme 1, 2). The crosslinking of the CS was through both, the rapid reaction between conjugated click chemistry pair TCO/Tz and the formation of Schiff bases between PEG-PALD and primary amines on CS. The mixture can form a solid hydrogel within 2 minutes. By optimizing the dosage of the co-crosslinker, adhesive strength, rheology, swelling ratio, and pore size of the hydrogel were characterized and compared, and the recipe that had the strongest adhesive strength was chosen for further animal study. Scheme 1. Step-by-step synthesis of the precursors and crosslinking of CS bioadhesives. Scheme 2. A depiction of the bonding structure between the CS bioadhesives and surrounding tissue. In this study, click chemistry-based CS bioadhesives were fabricated and evaluated for their ability to accelerate wound closure and promote wound healing. By taking advantage of the rapid click chemistry reaction time, they are able to tune the gelation time of the CS bioadhesives to be around 60-70 seconds for various clinical applications. Through introducing Schiff bases formed within the CS bioadhesives and between the CS bioadhesives and the surrounding tissue, the adhesive strength of the CS bioadhesives was significantly elevated. With the optimized formulation, the adhesive strength of the CS bioadhesives was 2.3 folds higher than that of fibrin glue. The quantitative in vitro cytotoxicity evaluations of the CS bioadhesives supported the application of this material in the medical field. Finally, with the application of the CS bioadhesives for wound closure in mice, it showed that the material produced small tissue gap, accelerated wound closure, and led to a better healing outcome compared with t...
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  • Engineering PEG-based hydrogels to foster efficient endothelial network formation in free-swelling and confined microenvironments
    Engineering PEG-based hydrogels to foster efficient endothelial network formation in free-swelling and confined microenvironments June 8,2020.
    Engineering PEG-based hydrogels can efficiently foster endothelial network formation in free-swelling and confined microenvironments Polyethylene glycol (PEG) and its derivatives are among the few polymers approved by the US FDA that can be used in biomedical products. The PEGl-based hydrogel has excellent flexibility and biocompatibility. Some PEG hydrogels can not only be degraded, but also can form bioactive site through modifying the connexins in a chemical way. In vitro tissue engineered models are expected to have significant impact on disease modeling and preclinical drug development. Reliable methods to induce microvascular networks in such microphysiological systems are needed to improve the size and physiological function of these models. By systematically engineering several physical and biomolecular properties of the cellular microenvironment (including crosslinking density, polymer density, adhesion ligand concentration, and degradability), the author Alexander Brown establish design principles that describe how synthetic matrix properties influence vascular morphogenesis in modular and tunable hydrogels based on commercial 8-arm poly (ethylene glycol) (PEG8a) macromers. The author applies these design principles to generate endothelial networks that exhibit consistent morphology throughout depths of hydrogel greater than 1 mm. These PEG8a-based hydrogels have relatively high volumetric swelling ratios (>1.5), which limits their utility in confined environments such as microfluidic devices. To overcome this limitation, the author mitigates swelling by incorporating a highly functional PEG-grafted alpha-helical poly (propargyl-l-glutamate) (PPLGgPEG) macromer along with the canonical 8-arm PEG8a macromer in gel formation. This hydrogel platform supports enhanced endothelial morphogenesis in neutral-swelling environments. Finally, the author incorporates PEG8a-PPLGgPEG gels into microfluidic devices and demonstrates improved diffusion kinetics and microvascular network formation in situ compared to PEG8a-based gels. If there is any copyright infringement, please contact us and we will remove the content at the first time. Sinopeg provide various NW poly(ethylene glycol) (PEG) products: 2KDa, 5KDa, 10KDa, 20KDa, etc. Products: Linear Monofunctional PEGs Linear Bifunctional PEGs Linear Heterofunctional PEGs Branched PEGs Multi-Arm Functional PEGs Functionally Grafted PEGs
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  • PEG hydrogel for in vivo hemostasis
    PEG hydrogel for in vivo hemostasis May 14,2020.
    A sealant can significantly improve the effect of visceral surgery; it can not only reduce intraoperative blood loss, but also reduce postoperative complications such as secondary hemorrhage and tissue adhesion, which are essential in surgical operations. However, the sealant currently used for in vivo hemostasis cannot address the needs in the modern aging society. The main challenges are its safeness, easiness of preparation and removal, and price. The commercial synthetic sealants are mainly made up of PEG, for example the 4-arm PEG hydrogel based on the ammonolysis reaction. Those sealants have advantages of high strength, strong adhesion and economic price, but the disadvantage is that they cannot be quickly degraded and can easily cause foreign body reaction in the wound that leads to healing delay.   In order to overcome the limitations of the existing PEG hydrogels, a new PEG sealant based on multi-arm PEG Succinimidyl Succinate (amide bond) has been jointly developed by Institute of Chemistry, Chinese Academy of Science and the General Hospital of People's Liberation Army.   The in vitro experiments show that SS glue has a better hemostatic effect than the previously developed SG and gauze. SS can quickly stanch the bleeding on the wound as well as prevent the adhesion issue after the operation. In contrast, SG and gauze both have different degree of postoperative adhesion when they are used for hemostasis. However, this is not the case for SS, as it is able to stop bleeding effectively even for patients taking anticoagulants, which cannot be achieved by the widely used fibrin glue.   The researchers compare the hemostatic effects of SS, SG and gauze on wounds. Among them, SS and SG can achieve rapid wound hemostasis, while gauze is much slower. And after a week of hemostasis, both SG and gauze have different degrees of adhesion while SS does not have such side effects. It indicates that SS not only can stop bleeding, but also acts as a physical barrier to prevent the wound from adhering to the surrounding tissues during the healing process (Figure a). Figure b compares the healing situation of wounds at different times after surgery. Figure c compares the separate hemostatic effects of SS and fibrin glue used in the wounds of a New Zealand white rabbit with anticoagulants. SS has a better hemostatic effect than fibrin glue in terms of speed and stability. The author further uses SS to perform the hemostasis experiment on a large wound surface (diameter: 25mm, depth: 10mm). Even if a coagulant is used, SS can effectively stop bleeding after a certain period of time. Sinopeg provide various NW poly(ethylene glycol) (PEG) products: 2KDa, 5KDa, 10KDa, 20KDa, etc. Products: Linear Monofunctional PEGs Linea...
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