Semi-field evaluation of a novel controlled release device using transfluthrin as spatial repellent to prevent entry of mosquitoes into military tents.

Mosquitoes can impact military operational readiness by transmission of disease-causing pathogens or through secondary effects, e.g., annoyance and bites. The focus of this research was to determine if an array of novel controlled release passive devices (CRPD) utilizing the spatial repellent, transfluthrin (TF), as the active ingredient could prevent entry of mosquitoes into military tents for up to 4 weeks. The TF-charged CRPDs were spaced along six strands of monofilament and hung across the tent entrance. Efficacy was evaluated with caged Aedes aegypti to indicate knockdown/mortality effects, and four species of free-flying mosquitoes, Ae. aegypti, Aedes taeniorhynchus, Anopheles quadrimaculatus and Culex quinquefasciatus, to indicate repellent effects. Bioassay cages containing Ae. aegypti were hung vertically at 0.5, 1.0 and 1.5 â€‹m above ground level at designated locations inside of the tents. Knockdown/mortality counts were made every 15 min for the first hour, then at 2, 4 and 24 h post-exposure. Free fliers were recaptured in BG traps operated from 4 to 24 h post-exposure. Knockdown/mortality was gradual until 4 h post-exposure. This increased to near 100% by 24 h in the treated tent but was < 2% in the control tent. There was a significant reduction in the recapture rates of all free-flying species in the treated tent compared with the control tent. Results indicate that TF-charged CRPDs can significantly reduce the numbers of mosquitoes entering military tents and that the four species were affected similarly by the TF. The needs for additional research are discussed.

Effect of pH Cycling Frequency on Glass-Ceramic Corrosion.

The effect of pH changes on the chemical durability of dental glass-ceramic materials was evaluated using weight loss and ion release levels. The hypothesis that increased pH changes will exhibit greater corrosion was investigated. The ion concentration was analyzed using inductively coupled plasma atomic emission spectrometer (ICP). The surface compositions were investigated using X-ray photoelectron spectroscopy (XPS). The surface morphologies were examined using scanning electron microscopy (SEM). Dental glass-ceramics were tested in constant immersion, 3-day cycling, and 1-day cycling with pH 10, pH 2, and pH 7 for 3, 15, and 30 days. The 1-d cycling group demonstrated the highest levels of weight loss compared with 3-d cycling and constant immersion. For the ion release, Si4+ and Ca2+ had the highest rates of release in 1-d cycling, whereas the Al3+ release rate with constant pH 2 was highest. The alteration/passivation layer that was formed on the surface of disks possibly prevented further dissolution of pH 10 corroded disks. XPS analysis demonstrated different surface compositions of corroded disks in pH 10 and pH 2. Si4+, K+, Na+, Al3+, and Ca2+ were detected on the surface of corroded pH 10 disks, whereas a Si4+ and P5+-rich surface formed on corroded pH 2 disks. SEM results demonstrated rougher surfaces for corroded disks in cycling conditions and pH 2 constant immersion. In conclusion, increased pH changes significantly promote the corrosion of dental glass-ceramic materials.

Olfactometric Comparison of the Volatile Insecticide, Metofluthrin, Through Behavioral Responses of Aedes albopictus (Diptera: Culicidae).

Testing behavioral response to insecticidal volatiles requires modifications to the existing designs of olfactometers. To create a testing apparatus in which there is no chemical memory to confound tests, we detail the technical aspects of a new tool with design influences from other olfactometry tools. In addition, this new tool was used to evaluate a novel formulation of metofluthrin for use as an outdoor residual treatment. After sourcing materials to prioritize glass and metal construction, a modular wind tunnel was developed that hybridizes wind tunnel and olfactometer specifications. Volatile contaminants were removed by strong ultraviolet light within the chamber before and between trials. Repellent trials were conducted with an experimental formulation of metofluthrin and a commercial formulation of esfenvalerate, prallethrin, and piperonyl butoxide (Onslaught Fast Cap) against Aedes albopictus (Skuse). Toxicant vapors were delivered with attractants from a lure with behavioral responses scored 20 min post-exposure. Upwind attraction to the attractant lure and the Onslaught Fast Cap plus lure resulted in 90 and 75% capture, respectively. In contrast, metofluthrin vapors resulted in less than 10% attraction, while also causing repellency, disorientation, knockdown, and mortality effects. Our findings demonstrated that an inert modular wind tunnel was functional for mitigating toxic secondary exposures of spatial repellents amidst complex behavioral analysis in mosquitoes. The resulting observations with formulated metofluthrin positively reinforce the merit of transitioning metofluthrin into expanded roles in mosquito management.

Carbodiimide Conjugation of Latent Transforming Growth Factor ß1 to Superparamagnetic Iron Oxide Nanoparticles for Remote Activation.

Conjugation of latent growth factors to superparamagnetic iron oxide nanoparticles (SPIONs) is potentially useful for magnetically triggered release of bioactive macromolecules. Thus, the goal of this work was to trigger the release of active Transforming Growth-Factor Beta (TGF-ß) via magnetic hyperthermia by binding SPIONs to the latent form of TGF-ß, since heat has been shown to induce release of TGF-ß from the latent complex. Commercially available SPIONS with high specific absorption rates (SAR) were hydrolyzed in 70% ethanol to create surface carboxylic acid conjugation sites for carbodiimide chemistry. Fourier-Transform Infra-Red (FTIR) analysis verified the conversion of maleic anhydride to maleic acid. 1-Ethyl-2-(3-dimethyulaminopropyl) carbodiimide (EDC) and N-hydroxysulfosuccinimide (Sulfo-NHS) were used to bind to the open conjugation sites of the SPION in order to graft latent TGF-ß onto the particles. The resulting conjugated particles were imaged with transmission electron microscopy (TEM), and the complexed particles were characterized by dynamic light scattering (DLS) and superconducting quantum interference device (SQUID) magnetometry. Enzyme-linked immunosorbent assay (ELISA) was used to assess the thermally triggered release of active TGF-ß from the latent complex, demonstrating that conjugation did not interfere with release. Results showed that latent TGF-ß was successfully conjugated to the iron oxide nanoparticles, and magnetically triggered release of active TGF-ß was achieved.

A Low-Cost, Passive Release Device for the Surveillance and Control of Mosquitoes.

Mosquitoes continue to be a major threat to global health, and the ability to reliably monitor, catch, and kill mosquitoes via passive traps is of great importance. Global, low-cost, and easy-to-use outdoor devices are needed to augment existing efforts in mosquito control that combat the spread of disease, such as Zika. Thus, we have developed a modular, portable, non-powered (passive), self-contained, and field-deployable device suitable for releasing volatiles with a wide range of applications such as attracting, repelling, and killing mosquitoes. This unique device relies on a novel nested wick and two-reservoir design that achieves a constant release of volatiles over several hundred hours. Devices loaded with one of either two compounds, geraniol or 1-methylpiperazine (MP), were tested in a controlled environment (32 °C and 70% relative humidity), and both compounds achieved a constant release from our devices at a rate of 2.4 mg/h and 47 mg/h, respectively. The liquid payload can be volatile attractants or repellants as well as mosquitocide-containing feeding solutions for capture and surveillance. This low-cost device can be utilized for both civilian and military mosquito control purposes, but it will be particularly important for protecting those in economically repressed environments, such as sub-Saharan Africa and Central and South America.

Antibacterial Properties of Charged TiN Surfaces for Dental Implant Application.

The formation and characterization of positively surface charged TiN surfaces were investigated for improving dental implant survival. Surface nitrogen atoms of a traditional TiN implant were converted to a positive charge by a quaternization reaction which greatly increased the antibacterial efficiency. Ti, TiN, and quaternized TiN samples were incubated with human patient subgingival bacteria for 4 hours at 37°C in an anaerobic environment with an approximate 40% reduction in counts on the quaternized surface over traditional Ti and TiN. The samples were challenged with Streptococcus Mutans and fluorescent imaging confirmed significant reduction in the quaternized TiN over the traditional Ti and TiN. Contact angle measurement and X-Ray Photoelectron Spectroscopy (XPS) were utilized to confirm the surface chemistry changes. The XPS results found the charged quaternized nitrogen peak at 399.75 eV that is unique to the quaternized sample.

Detection and quantification of trace airborne transfluthrin concentrations via air sampling and thermal desorption gas chromatography-mass spectrometry.

A rapid thermal desorption-gas chromatography-electron ionization-mass spectrometry (TD-GC-EI-MS) method for airborne transfluthrin detection is studied. Active air sampling of 9 L over 1 h at 23 °C through a Tenax®-loaded tube resulted in efficient capture of airborne transfluthrin. Subsequent thermal desorption was employed to achieve an LOD of 2.6 ppqv (parts per quadrillion by volume). A minimum primary desorption temperature of 300 °C is necessary for optimal recovery of sample from the Tenax® adsorbent. The matrix effects of indoor air lead to an error of 10.9% and 10.5% recovery of sample (10 pg and 100 pg loaded tubes, respectively). The linear range was 74-74,000 ppqv with a correlation coefficient of 0.9981. Active air sampling of a novel passive release device revealed a ∼150 pg/L airborne concentration gradient over 1 m, providing spatial characterization of the device's performance. This efficient method allows for the remote collection of samples and rapid analysis of airborne transfluthrin from industrial applications, optimization studies of commercial products as well as domestic/household monitoring.

Gradual attenuation of a congenital extrahepatic portosystemic shunt with a self-retaining polyacrylic acid-silicone device in 6 dogs.

OBJECTIVE: To determine the ability of a polyacrylic acid-silicone radiolucent self-retaining gradual occlusion device (PAS-OD) to attenuate congenital extrahepatic portosystemic shunts (EHPSS) in dogs. STUDY DESIGN: Prospective clinical trial. ANIMALS: Six client-owned dogs with single, congenital EHPSS. METHODS: Serum bile acids (SBA), abdominal ultrasonography, and computed tomographic angiography (CTA) were performed preoperatively and at 4 and 8 weeks postoperatively. Each dog was treated for EHPSS by placement of a PAS-OD. RESULTS: PAS-OD were placed without complication an average of 4.3 seconds (range, 3-7) after isolation of the shunt. Median surgical time was 38.5 minutes (range, 28-84) including concurrent procedures. All dogs recovered from surgery without complications. SBA were normal in 5 of 6 dogs at 4 and 8 weeks after surgery. The shunt was completely attenuated in 2 of 6 dogs at 4 weeks and in 4 of 6 dogs at 8 weeks, without evidence of acquired shunt formation in any dog. The size and velocity of the portal vasculature were improved in 5 of 6 dogs according to 8-week postoperative CTA and ultrasonography results, respectively. The remaining dog had a persistently decreased portal vasculature size but a normal velocity according to 8-week postoperative CTA and ultrasound results, respectively. CONCLUSION: The PAS-OD led to complete attenuation in 4 of 6 dogs and partial attenuation with mild residual flow of 2 EHPSS over an 8-week period in dogs. CLINICAL SIGNIFICANCE: The PAS-OD is a new option for gradual occlusion of congenital EHPSS over 8 weeks.

An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats.

BACKGROUND: A new post-myocardial infarction (MI) therapy is injection of high-water-content polymeric biomaterial gels (hydrogels) into damaged myocardium to modulate cardiac negative remodeling and preserve heart function. METHODS: We investigated the therapeutic potential of a novel gelatinized alginate hydrogel with a unique microstructure of uniform capillary-like channels (termed Capgel). Shortly (48h) after induced anterior MI, Sprague Dawley rats received intramyocardial injection of Capgel directly into the antero-septal wall at the infarct border zone (n=12) or no injection (n=10, controls). Echocardiograms were performed at 48h (week 0) and 4weeks (week 4) to evaluate left ventricular function. RESULTS: Echocardiograms showed 27% improvement of left ventricular systolic function over time with gel injection: fractional shortening increased from 26±3% at week 0 to 33±2% at week 4 (p=0.001). Capgel was present at the injection site after 4weeks, but was minimal at 8weeks. The remaining gel was heavily populated by CD68(+) macrophages with CD206(+) clusters and blood vessels. An in vitro experiment was performed to assess Angiotensin-(1-7) released from Capgel. Angiotensin-(1-7) was released from the Capgel in a sustained manner for 90days. CONCLUSIONS: Use of Capgel, a degradable, bioactive hydrogel composed of gelatinized capillary-alginate gel, appears safe for intramyocardial injection, is associated with improved left ventricular function after MI in rats, and may provide a long-term supply of Angiotensin-(1-7).

Assessment of the attenuation of an intra-abdominal vein by use of a silicone-polyacrylic acid gradual venous occlusion device in dogs and cats.

OBJECTIVE To evaluate the closure rate and completeness of closure for a silicone-polyacrylic acid gradual venous occlusion device placed around an intra-abdominal vein to simulate gradual occlusion of an extrahepatic portosystemic shunt. ANIMALS 3 purpose-bred cats and 2 purpose-bred dogs. PROCEDURES The device was surgically placed around an external (cats) or internal (dogs) iliac vein. Computed tomographic angiography was performed at the time of surgery and 2, 4, and 6 weeks after surgery. Ultrasonographic examinations of blood flow through the vein within the device were performed at the time of surgery and at weekly intervals thereafter. Dogs were euthanized 6 weeks after surgery, and the external iliac veins were harvested for histologic examination. RESULTS The prototype gradual venous occlusion device was successfully placed in all animals, and all animals recovered without complications following the placement procedure. The vessel was completely occluded in 2 cats by 6 weeks after surgery, as determined on the basis of results of CT and ultrasonography; there was incomplete occlusion with a luminal diameter of 1.5 mm in the other cat by 6 weeks after surgery. The vessel was completely occluded in both dogs by 6 weeks after surgery. Histologic examination of the external iliac veins obtained from the dogs revealed minimal inflammation of the vessel wall and no thrombus formation. CONCLUSIONS AND CLINICAL RELEVANCE The prototype device induced gradual attenuation of an intra-abdominal vessel over a 6-week period. This device may provide another option for gradual occlusion of extrahepatic portosystemic shunts.

Repurposed biological scaffolds: kidney to pancreas.

Advances in organ regeneration have been facilitated by gentle decellularization protocols that maintain distinct tissue compartments, and thereby allow seeding of blood vessels with endothelial lineages separate from populations of the parenchyma with tissue-specific cells. We hypothesized that a reconstituted vasculature could serve as a novel platform for perfusing cells derived from a different organ: thus discordance of origin between the vascular and functional cells, leading to a hybrid repurposed organ. The need for a highly vascular bed is highlighted by tissue engineering approaches that involve transplantation of just cells, as attempted for insulin production to treat human diabetes. Those pancreatic islet cells present unique challenges since large numbers are needed to allow the cell-to-cell signaling required for viability and proper function; however, increasing their number is limited by inadequate perfusion and hypoxia. As proof of principle of the repurposed organ methodology we harnessed the vasculature of a kidney scaffold while seeding the collecting system with insulin-producing cells. Pig kidneys were decellularized by sequential detergent, enzymatic and rinsing steps. Maintenance of distinct vascular and collecting system compartments was demonstrated by both fluorescent 10 micron polystyrene microspheres and cell distributions in tissue sections. Sterilized acellular scaffolds underwent seeding separately via the artery (fibroblasts or endothelioma cells) and retrograde (murine ßTC-tet cells) up the ureter. After three-day bioreactor incubation, histology confirmed separation of cells in the vasculature from those in the collecting system. ßTC-tet clusters survived in tubules, glomerular Bowman's space, demonstrated insulin immunolabeling, and thereby supported the feasibility of kidney-to-pancreas repurposing.

Synthesis of polymeric phosphonates for selective delivery of radionuclides to osteosarcoma.

Discussed in detail is the synthesis and primary structure characterization of two polymers aimed at advancing the treatment of pediatric osteosarcoma. These polymers are designed to systemically deliver radiometals specifically to osteosarcomas using the passive targeting mechanism of enhanced permeability and retention (the EPR effect). The approach begins with the synthesis of a polymer capable of binding radiometals, for which prior data show improved site-specific targeting of solid tumors. Building on this success, a second polymer has been designed for improving the efficacy of currently available radionuclide therapies by incorporating the FDA-approved small-molecule ligand Quadramet directly onto the polymer structure. Time-activity curves of the phosphonate-functionalized polymers show rapid clearance from the central compartment and nontargeted organs, with up to 65% of injected activity being excreted within 3 hours. Both polymer ligands demonstrate good osteosarcoma targeting capability with little to no uptake in organs associated with the dose-limiting bone marrow. Additionally, biodistribution studies in nonosseous tumor models demonstrate the tumor targeting mechanism of the polymer ligands, which appears to be influenced by the high affinity of the phosphonate functionality for the positively charged hydroxyapatite mineral found in bone tumors.

Materials characterization of Feraheme/ferumoxytol and preliminary evaluation of its potential for magnetic fluid hyperthermia.

Feraheme, is a recently FDA-cleared superparamagnetic iron oxide nanoparticle (SPION)-based MRI contrast agent that is also employed in the treatment of iron deficiency anemia. Feraheme nanoparticles have a hydrodynamic diameter of 30 nm and consist of iron oxide crystallites complexed with a low molecular weight, semi-synthetic carbohydrate. These features are attractive for other potential biomedical applications such as magnetic fluid hyperthermia (MFH), since the carboxylated polymer coating affords functionalization of the particle surface and the size allows for accumulation in highly vascularized tumors via the enhanced permeability and retention effect. This work presents morphological and magnetic characterization of Feraheme by transmission electron microscopy (TEM), Energy dispersive X-ray spectroscopy (EDX), and superconducting quantum interference device (SQUID) magnetometry. Additionally, the results of an initial evaluation of the suitability of Feraheme for MFH applications are described, and the data indicate the particles possess promising properties for this application.

Detailed analysis of polymer response to delivery balloon expansion of drug-eluting stents versus bare metal stents.

AIMS: We sought to describe the response of the polymer surface of drug-eluting stents (DES) to delivery balloon expansion, including quantitation of any resulting detached microparticles. METHODS AND RESULTS: We expanded the US Food and Drug Administration (FDA)-approved first- and second-generation DES in a vacuum filtration system and used optical and scanning electron microscopy to image the polymer surface, filters and delivery balloons. DES were expanded under a range of conditions, from in vitro conditions used for FDA regulatory submissions to human in vivo conditions. Dispersive Raman spectroscopy was used for definitive identification of microparticles. All polymer surfaces were topographically disturbed over an average of 4.6%-100% of the surface area imaged. Disturbances ranged from deformation (including peeling) to complete delamination. The dimensions of detached microparticles were 2-350 µm. The extent and nature of surface disturbances and microparticles were primarily a function of polymer composition (p<0.001 for 8/10 disturbance types/locations) and were independent of expansion condition (p=0.100 to 0.989 for 9/10 disturbance types/locations). CONCLUSIONS: Balloon expansion of first- and second-generation DES disturbs the polymer surface and can cause detachment of microparticles; each is functionally related to the specific polymer but not to expansion condition. Disturbance "roughness" and detached microparticles may contribute to DES limitations.

A degradable, bioactive, gelatinized alginate hydrogel to improve stem cell/growth factor delivery and facilitate healing after myocardial infarction.

Despite remarkable effectiveness of reperfusion and drug therapies to reduce morbidity and mortality following myocardial infarction (MI), many patients have debilitating symptoms and impaired left ventricular (LV) function highlighting the need for improved post-MI therapies. A promising concept currently under investigation is intramyocardial injection of high-water content, polymeric biomaterial gels (e.g., hydrogels) to modulate myocardial scar formation and LV adverse remodeling. We propose a degradable, bioactive hydrogel that forms a unique microstructure of continuous, parallel capillary-like channels (Capgel). We hypothesize that the innovative architecture and composition of Capgel can serve as a platform for endogenous cell recruitment and drug/cell delivery, therefore facilitating myocardial repair after MI.

Mouse stem cells seeded into decellularized rat kidney scaffolds endothelialize and remodel basement membranes.

INTRODUCTION: To address transplant organ shortage, a promising strategy is to decellularize kidneys in a manner that the scaffold retains signals for seeded pluripotent precursor cells to differentiate and recapitulate native structures: matrix-to-cell signaling followed by cell-cell and cell-matrix interactions, thereby remodeling and replacing the original matrix. This would reduce scaffold antigenicity and enable xeno-allografts. RESULTS: DAPI-labeled cells in arterial vessels and glomeruli were positive for both endothelial lineage markers, BsLB4 and VEGFR2. Rat scaffold's basement membrane demonstrated immunolabeling with anti-mouse laminin ß1. Labeling intensified over time with 14 day incubations. CONCLUSION: We provide new evidence for matrix-to-cell signaling in acellular whole organ scaffolds that induces differentiation of pluripotent precursor cells to endothelial lineage. Production of mouse basement membrane supports remodeling of host (rat)-derived scaffolds and thereby warrants further investigation as a promising approach for xenotransplantation. METHODS: We previously showed that murine embryonic stem cells arterially seeded into acellular rat whole kidney scaffolds multiply and demonstrate morphologic, immunohistochemical and gene expression evidence for differentiation. Vascular cell endothelialization was now further tested by endothelial specific BsLB4 lectin and anti-VEGFR2 (Flk1) antibodies. Remodeling of the matrix basement membranes from rat to mouse ("murinization") was assessed by a monoclonal antibody specific for mouse laminin ß1 chain.

Polymer-coated cannulas for the reduction of backflow during intraparenchymal infusions.

Infusate backflow or leak-back along the cannula track can occur during intraparenchymal infusions resulting in non-specific targeting of therapeutic agents. The occurrence of backflow depends on several variables including cannula radius, infusate flow rate, and tip location. In this study, polymer coatings that swell in situ were developed and tested with in vitro hydrogel experiments for backflow reduction. Coatings were applied to the external cannula surface in a dual layer arrangement with a poly(vinyl alcohol) outer layer atop an inner poly(ethylene oxide) and alginate layer. Once these coated cannulas were inserted and allotted an 8-10 min waiting period for hydration, backflow during infusions of 4.0 µl of a macromolecular tracer (Evans Blue labeled albumin) was reduced significantly under flow rates of 0.3-0.6 µl/min, allowing for more effective distribution within targeted regions. Polymer coating thicknesses before and after hydrations were 0.035 and 0.370 mm, respectively. Also, backflow data was fit to a model to estimate the effective local compressive stress caused by the hydrated polymers. After withdrawal of the cannula from the insertion site, the hydrated polymer coatings remained within the cavity left in the hydrogel tissue phantom and formed a seal at the infusion site that prevented further backflow during needle withdrawal. Ex vivo infusions in excised porcine brain tissues also showed significant backflow reduction while also demonstrating the ability to leave a polymer seal in the tissue cavity after cannula removal. Thus, application of these polymers as needle or cannula coatings offers a potentially simple method to improve targeting for local drug delivery.

Monocyte chemotactic protein-1 promotes inflammatory vascular repair of murine carotid aneurysms via a macrophage inflammatory protein-1α and macrophage inflammatory protein-2-dependent pathway.

BACKGROUND: Up to 5% of the population may have a brain aneurysm. If the brain aneurysm ruptures, there is >50% mortality, and more than one third of survivors are dependent. Brain aneurysms detected before rupture can be treated to prevent rupture, or ruptured aneurysms can be treated to prevent rerupture. Endovascular coiling of brain aneurysms is the treatment of choice for some aneurysms; however, up to one quarter of aneurysms may recur. The coiled aneurysms that do not recur are characterized by inflammatory intra-aneurysmal tissue healing; therefore, we studied the biology of this process, specifically the role of monocyte chemotactic protein-1 (MCP-1), a cytokine known for tissue healing. METHODS AND RESULTS: We created coils with a 50:50 poly-dl-lactic glycolic acid (PLGA) coating that released MCP-1 at 3 different doses (100 µg/mL, 1 mg/mL, and 10 mg/mL) and performed a dose-response study for effect on intra-aneurysmal tissue healing in a murine carotid aneurysm model. We then demonstrated that MCP-1 (100 µg/mL)-releasing coils promote significantly greater aneurysm tissue in-growth than bare platinum or PLGA-only coils. We show that MCP-1 recruits the migration of fibroblasts, macrophages, smooth muscle cells, and endothelial cells in vitro in cell migration assays and in vivo in murine carotid aneurysms. Using gfp(+) bone marrow-transplant chimeric mice, we demonstrate that the MCP-1-recruited fibroblasts and macrophages are derived from the bone marrow. We demonstrate that this MCP-1-mediated vascular inflammatory repair occurs via a macrophage inflammatory protein (MIP)-1α- and MIP-2-dependent pathway. MCP-1 released from coiled murine aneurysms causes significant upregulation of MIP-1α and MIP-2 expression by cytokine array assay. Blocking MIP-1α and MIP-2 with antagonist antibody causes a significant decrease in MCP-1-mediated intra-aneurysmal tissue healing. CONCLUSION: Our findings suggest that MCP-1 has a critical role in promoting inflammatory intra-aneurysmal tissue healing in an MIP-1α- and MIP-2-dependent pathway.

Gelatinized copper-capillary alginate gel functions as an injectable tissue scaffolding system for stem cell transplants.

In severe hypoxic-ischemic brain injury, cellular components such as neurons and astrocytes are injured or destroyed along with the supporting extracellular matrix. This presents a challenge to the field of regenerative medicine since the lack of extracellular matrix and supporting structures makes the transplant milieu inhospitable to the transplanted cells. A potential solution to this problem is the use of a biomaterial to provide the extracellular components needed to keep cells localized in cystic brain regions, allowing the cells to form connections and repair lost brain tissue. Ideally, this biomaterial would be combined with stem cells, which have been proven to have therapeutic potentials, and could be delivered via an injection. To study this approach, we derived a hydrogel biomaterial tissue scaffold from oligomeric gelatin and copper-capillary alginate gel (GCCAG). We then demonstrated that our multipotent astrocytic stem cells (MASCs) could be maintained in GCCAG scaffolds for up to 2 weeks in vitro and that the cells retained their multipotency. We next performed a pilot transplant study in which GCCAG was mixed with MASCs and injected into the brain of a neonatal rat pup. After a week in vivo, our results showed that: the GCCAG biomaterial did not cause a significant reactive gliosis; viable cells were retained within the injected scaffolds; and some delivered cells migrated into the surrounding brain tissue. Therefore, GCCAG tissue scaffolds are a promising, novel injectable system for transplantation of stem cells to the brain.