We have developed a local anesthetic-eluting suture system which would combine the function and ubiquity of the suture for surgical repair with the controlled release properties of a biodegradable ...polymeric matrix. Drug-free and drug-loaded poly(lactic-co-glycolic acid) (PLGA) sutures were fabricated by electrospinning, with or without the local anesthetic bupivacaine. The tensile strength of the electrospun sutures decreased as drug content increased, but strains remained relatively similar across all groups. Sutures released their entire drug payload over the course of 12days and maintained approximately 12% of their initial tensile strength after 14days of incubation in vitro. In a rat skin wound model, local analgesia was achieved 1day after surgery and lasted approximately 1week in 90% of treated animals (n=10, p<0.05), and all wounds were able to heal normally without the need for further reinforcement. The sutures caused tissue reaction in vivo that was comparable to that seen with a commercially available suture composed of PLGA. Such sutures may enhance perioperative analgesia and mitigate the need for standard postoperative opioid analgesics.
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Adhesive hydrogels have been recently proposed as a potential option to seal and treat gastric perforation (GP) which causes high mortality despite advancements in surgical treatments. However, to be ...effective, the hydrogels must have sufficient tissue adhesiveness, tough mechanical property, tunable biodegradability and ideally are easy to apply and form. Herein, we report an adhesive and resilient hydrogel for the sealing and treatment of gastric perforation. The hydrogel consists of a bioactive, transglutaminase (TG)-crosslinked gelatin network and a dynamic, borate-crosslinked poly-N-Tris(hydroxymethyl)methylacrylamide (PTH) network. The hydrogel can be formed in situ, facilitating easy delivery to the GP and allowing for precise sealing of the defects. In vivo experiments, using a perforated stomach mouse model, shows that the adhesive hydrogel plug effectively seals GP defects and promotes gastric mucosa regeneration. Overall, this hydrogel represents a promising biomaterial for GP treatment.
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•The interpenetrate double network hydrogel plug can be formed in situ with strong adhesiveness and toughness.•The hydrogel plug could adhere to the GP site and withstand the peristaltic movement of the stomach.•The hydrogel plug can effectively treated the GP and promoted mucosa regeneration in a mouse model.
In vivo implantation of sterile materials and devices results in a foreign body immune response leading to fibrosis of implanted material. Neutrophils, one of the first immune cells to be recruited ...to implantation sites, have been suggested to contribute to the establishment of the inflammatory microenvironment that initiates the fibrotic response. However, the precise numbers and roles of neutrophils in response to implanted devices remains unclear. Using a mouse model of peritoneal microcapsule implantation, we show 30-500 fold increased neutrophil presence in the peritoneal exudates in response to implants. We demonstrate that these neutrophils secrete increased amounts of a variety of inflammatory cytokines and chemokines. Further, we observe that they participate in the foreign body response through the formation of neutrophil extracellular traps (NETs) on implant surfaces. Our results provide new insight into neutrophil function during a foreign body response to peritoneal implants which has implications for the development of biologically compatible medical devices.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Continuous fibers are described having concentric layer or aligned sphere microphase-separated, styrene-isoprene block copolymer morphologies. The fibers are obtained by a two-fluid coaxial ...electrospinning technique in which the desired block copolymer is encapsulated as the core component within a polymer shell having a high glass transition temperature (T g). The fibers range in diameter from 300 to 800 nm, and the block copolymer core ranges from 50 to 500 nm. Subsequent annealing of the fibers above the upper T g of the block copolymer but below the T g of the shell polymer results in microphase separation of the block copolymer under cylindrical confinement. The resulting fibers exhibit improved long-range order. This two-step strategy creates the opportunity to fabricate continuous nanofibers with periodic internal structure.
Fibers with long-range ordered internal structures have applications in various areas such as photonic band gap fibers, optical waveguides, wearable power, sensors, and sustained drug release. Up to ...now, such fibers have been formed by melt extrusion or drawing from a macroscopic preformed rod and were typically limited to diameters >10 μm with internal features >1 μm (Abouraddy, A. F.; et al. Nat. Mater. 2007, 6, 336). We describe a new class of continuous fibers and fibrous membranes with long-range ordered concentric lamellar structure that have fiber diameters and feature sizes 2−3 orders of magnitude smaller than those made by conventional methods. These fibers are created through confined self-assembly of block copolymers within core−shell electrospun filaments. In contrast to the copolymer in bulk or thin films, the domains of the concentric lamellar structure are shown here to vary quantitatively with (radial) position and to exhibit a novel dislocation that accommodates variations in fiber diameter robustly, permitting for the first time the realization of long-range order in technologically meaningful, continuous fibers with approximately 300 nm diameter and 50 nm radial period.
Analogous to an assembly line, we employed a modular design for the high-throughput study of 1,536 structurally distinct nanoparticles with cationic cores and variable shells. This enabled ...elucidation of complexation, internalization, and delivery trends that could only be learned through evaluation of a large library. Using robotic automation, epoxide-functionalized block polymers were combinatorially cross-linked with a diverse library of amines, followed by measurement of molecular weight, diameter, RNA complexation, cellular internalization, and in vitro siRNA and pDNA delivery. Analysis revealed structure-function relationships and beneficial design guidelines, including a higher reactive block weight fraction, stoichiometric equivalence between epoxides and amines, and thin hydrophilic shells. Cross-linkers optimally possessed tertiary dimethylamine or piperazine groups and potential buffering capacity. Covalent cholesterol attachment allowed for transfection in vivo to liver hepatocytes in mice. The ability to tune the chemical nature of the core and shell may afford utility of these materials in additional applications.
Pesticide exposure, heavy metal pollution, and biological stressors drive a worldwide, ongoing, and rapid population decline of the crucial pollinator honeybee. Drastic colony loss of honeybees may ...well precipitate a food security crisis. Here a systematic review was conducted, examining reports on a global scale to propose a bench line for common pesticides and potentially toxic element (PTE) residue levels in plant rewards and honeybees and to assess the health risk of chemical residues via oral exposure to honeybees. Relevant articles were retrieved from Scopus, PubMed, ISI Web of Science, and Embase. Recent findings on how chemical and biological stressors cripple honeybee health, and conservation techniques were also summarized. We identified a number of chemical residues at lethal or sublethal risk to honeybees based on their average concentrations, as well as primary evidence pertaining to the bio-accumulative propensity of certain substances. Moreover, combinations of pesticide stressors (“pesticide cocktails”), which are frequently encountered in agricultural landscapes, often interact synergistically with honeybee health via detoxification suppression. Finally, we discuss and describe the relevance of novel, biotechnology-based, approaches to counteract agrochemical and PTE poisoning.
Abstract The non-specific host response to implanted biomaterials is often a key challenge of medical device design. To evaluate biocompatibility, measuring the release of reactive oxygen species ...(ROS) produced by inflammatory cells in response to biomaterial surfaces is a well-established method. However, the detection of ROS in response to materials implanted in vivo has not yet been demonstrated. Here, we develop a bioluminescence whole animal imaging approach to observe ROS released in response to subcutaneously-implanted materials in live animals. We compared the real-time generation of ROS in response to two representative materials, polystyrene and alginate, over the course of 28 days. High levels of ROS were observed near polystyrene, but not alginate implants, and persisted throughout the course of 28 days. Histological analysis revealed that high levels of ROS correlated not only with the presence of phagocytic cells at early timepoints, but also fibrosis at later timepoints, suggesting that ROS may be involved in both the acute and chronic phase of the foreign body response. These data are the first in vivo demonstration of ROS generation in response to implanted materials, and describe a novel technique to evaluate the host response.
The targeted delivery of therapeutics to tumors remains an important challenge in cancer nanomedicine. Attaching nanoparticles to cells that have tumoritropic migratory properties is a promising ...modality to address this challenge. Here we describe a technique to create nanoparticulate cellular patches that remain attached to the membrane of cells for up to 2 days. NeutrAvidin-coated nanoparticles were anchored on cells possessing biotinylated plasma membrane. Human bone marrow derived mesenchymal stem cells with nanoparticulate patches retained their inherent tumoritropic properties as shown using a tumor model in a 3D extracellular matrix. Additionally, human umbilical vein endothelial cells with nanoparticulate patches were able to retain their functional properties and form multicellular structures as rapidly as unmodified endothelial cells. These results provide a novel strategy to actively deliver nanostructures and therapeutics to tumors utilizing stem cells as carriers and also suggest that nanoparticulate cellular patches may have applications in tissue regeneration.
Highly efficient photocatalytically active TiO2‐coated polymer fibers are prepared using a facile and universal method involving layer‐by‐layer assembly of TiO2 nanoparticles and POSS molecules on ...various electrospun fibers. The TiO2‐coated fibers display excellent photocatalytic properties in degradation of allyl alcohol under UV illumination, without degradation of substrates.
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