Adam M. Behrens

Hemostatic strategies for traumatic and surgical bleeding

Wide interest in new hemostatic approaches has stemmed from unmet needs in the hospital and on the battlefield. Many current commercial hemostatic agents fail to fulfill the design requirements of safety, efficacy, cost, and storage. Academic focus has led to the improvement of existing strategies as well as new developments. This review will identify and discuss the three major classes of hemostatic approaches: biologically derived materials, synthetically derived materials, and intravenously administered hemostatic agents. The general class is first discussed, then specific approaches discussed in detail, including the hemostatic mechanisms and the advancement of the method. As hemostatic strategies evolve and synthetic-biologic interactions are more fully understood, current clinical methodologies will be replaced.

Sprayable Elastic Conductors Based on Block Copolymer Silver Nanoparticle Composites

Block copolymer silver nanoparticle composite elastic conductors were fabricated through solution blow spinning and subsequent nanoparticle nucleation. The reported technique allows for conformal deposition onto nonplanar substrates. We additionally demonstrated the ability to tune the strain dependence of the electrical properties by adjusting nanoparticle precursor concentration or localized nanoparticle nucleation. The stretchable fiber mats were able to display electrical conductivity values as high as 2000 ± 200 S/cm with only a 12% increase in resistance after 400 cycles of 150% strain. Stretchable elastic conductors with similar and higher bulk conductivity have not achieved comparable stability of electrical properties. These unique electromechanical characteristics are primarily the result of structural changes during mechanical deformation. The versatility of this approach was demonstrated by constructing a stretchable light emitting diode circuit and a strain sensor on planar and nonplanar substrates.

A Review of the Fundamental Principles and Applications of Solution Blow Spinning

Solution blow spinning (SBS) is a technique that can be used to deposit fibers in situ at low cost for a variety of applications, which include biomedical materials and flexible electronics. This review is intended to provide an overview of the basic principles and applications of SBS. We first describe a method for creating a spinnable polymer solution and stable polymer solution jet by manipulating parameters such as polymer concentration and gas pressure. This method is based on fundamental insights, theoretical models, and empirical studies. We then discuss the unique bundled morphology and mechanical properties of fiber mats produced by SBS, and how they compare with electrospun fiber mats. Applications of SBS in biomedical engineering are highlighted, showing enhanced cell infiltration and proliferation versus electrospun fiber scaffolds and in situ deposition of biodegradable polymers. We also discuss the impact of SBS in applications involving textiles and electronics, including ceramic fibers and conductive composite materials. Strategies for future research are presented that take advantage of direct and rapid polymer deposition via cost-effective methods.

Biodegradable‐Polymer‐Blend‐Based Surgical Sealant with Body‐Temperature‐Mediated Adhesion

The development of practical and efficient surgical sealants has the propensity to improve operational outcomes. A biodegradable polymer blend is fabricated as a nonwoven fiber mat in situ. After direct deposition onto the tissue of interest, the material transitions from a fiber mat to a film. This transition promotes polymer-substrate interfacial interactions leading to improved adhesion and surgical sealant performance.

FVII Dependent Coagulation Activation in Citrated Plasma by Polymer Hydrogels

Polymer hydrogels containing positively charged functional groups were used to investigate the critical material and biological components of FVII activation and subsequent fibrin formation in citrated plasma. A FVIIa ELISA confirmed the ability of the polymer to induce FVII activation and provided insight into the material parameters which were influential in this activation. Experiments utilizing coagulation factor depleted and inhibited plasmas indicated that FVII, FX, FII, and FI are all vital to the process outlining the general mechanism of fibrin formation from the onset of FVII activation. Dynamic mechanical analysis and swelling experiments were used to establish a critical correlation between polymer microstructure and FVII activation.

Simple and inexpensive quantification of ammonia in whole blood.

Quantification of ammonia in whole blood has applications in the diagnosis and management of many hepatic diseases, including cirrhosis and rare urea cycle disorders, amounting to more than 5 million patients in the United States. Current techniques for ammonia measurement suffer from limited range, poor resolution, false positives or large, complex sensor set-ups. Here we demonstrate a technique utilizing inexpensive reagents and simple methods for quantifying ammonia in 100 μL of whole blood. The sensor comprises a modified form of the indophenol reaction, which resists sources of destructive interference in blood, in conjunction with a cation-exchange membrane. The presented sensing scheme is selective against other amine containing molecules such as amino acids and has a shelf life of at least 50 days. Additionally, the resulting system has high sensitivity and allows for the accurate reliable quantification of ammonia in whole human blood samples at a minimum range of 25 to 500 μM, which is clinically for rare hyperammonemic disorders and liver disease. Furthermore, concentrations of 50 and 100 μM ammonia could be reliably discerned with p = 0.0001.

Rapid fabrication of poly(DL-lactide) nanofiber scaffolds with tunable degradation for tissue engineering applications by air-brushing

Polymer nanofiber based materials have been widely investigated for use as tissue engineering scaffolds. While promising, these materials are typically fabricated through techniques that require significant time or cost. Here we report a rapid and cost effective air-brushing method for fabricating nanofiber scaffolds using a simple handheld apparatus, compressed air, and a polymer solution. Air-brushing also facilities control over the scaffold degradation rate without adversely impacting architecture. This was accomplished through a one step blending process of high (M w  ≈  100 000 g mol(-1)) and low (M w  ≈  25 000 g mol(-1)) molecular weight poly(DL-lactide) (PDLLA) polymers at various ratios (100:0, 70:30 and 50:50). Through this approach, we were able to control fiber scaffold degradation rate while maintaining similar fiber morphology, scaffold porosity, and bulk mechanical properties across all of the tested compositions. The impact of altered degradation rates was biologically evaluated in human bone marrow stromal cell (hBMSC) cultures for up to 16 days and demonstrated degradation rate dependence of both total DNA concentration and gene regulation.

In vitro and in vivo evaluation of polymer hydrogels for hemorrhage control

In vitro and in vivo experimentation of various synthetic polymer hydrogels was conducted to establish some of the integral material properties that influence hemostasis. In vitro swelling experiments suggested that positive electrostatic charge was a key determinant of the ability of a polymer hydrogel to absorb physiological fluids, e.g. human plasma and blood. In vitro testing using unadulterated sheep blood suggested positive electrostatic charge and crosslink density were key determinants of the ability of a material to induce or enhance clot formation. Hydrogel formulations composed of higher amounts of positive electrostatic charge and lower crosslink density were able to effectively induce and enhance clot formation in the presence of a coagulation cascade activator. In vivo experimentation confirmed that hydrogels containing higher electrostatic charge and low crosslink density are more effective at fostering the formation of a robust hemostatic plug to control blood loss.

Solution blow spun polymer: A novel preclinical surgical sealant for bowel anastomoses

BACKGROUND Solution blow spinning is a technique for depositing polymer fibers with promising potential use as a surgical sealant. This study assessed the feasibility and efficacy of solution blow spun polymer (BSP) for sealing bowel perforations in a mouse model of partial cecal transection. We then evaluated its use for reinforcing a surgical anastomosis in a preclinical piglet model. METHODS Three commercially available surgical sealants (fibrin glue, polyethylene glycol (PEG) hydrogel, and cyanoacrylate) were compared to BSP in the ability to seal partially transected cecum in mice. For anastomosis feasibility testing in a piglet model, piglets were subjected to small bowel transection with sutured anastomosis reinforced with BSP application. Outcome measures included anastomotic burst pressure, anastomotic leak rate, 14-day survival, and complication rate. RESULTS For the mouse model, the survival rates for the sealants were 30% for fibrin glue, 20% for PEG hydrogel, 78% for cyanoacrylate, and 67% for BSP. Three of 9 mice died after BSP administration because of perforation leak, failure to thrive with partial obstruction at the perforation site, and unknown causes. All other mice died of perforation leak. The mean burst pressure at 24h was significantly higher for BSP (81mm Hg) when compared to fibrin glue (6mm Hg, p=0.047) or PEG hydrogel (10mm Hg, p=0.047), and comparable to cyanoacrylate (64mm Hg, p=0.91). For piglets, 4 of 4 animals survived at 14days. Mean burst pressures at time of surgery were 37±5mm Hg for BSP and 11±9mm Hg for suture-only controls (p=0.09). CONCLUSIONS Solution blow spinning may be an effective technique as an adjunct for sealing of gastrointestinal anastomosis. Further preclinical testing is warranted to better understand BSP properties and alternative surgical applications.

Zeolite-loaded alginate-chitosan hydrogel beads as a topical hemostat

Hemorrhage is the leading cause of preventable death after a traumatic injury, and the largest contributor to loss of productive years of life. Hemostatic agents accelerate hemostasis and help control hemorrhage by concentrating coagulation factors, acting as procoagulants and/or interacting with erythrocytes and platelets. Hydrogel composites offer a platform for targeting both mechanical and biological hemostatic mechanisms. The goal of this work was to develop hydrogel particles composed of chitosan, alginate, and zeolite, and to assess their potential to promote blood coagulation via multiple mechanisms: erythrocyte adhesion, factor concentration, and the ability to serve as a mechanical barrier to blood loss. Several particle compositions were synthesized and characterized. Hydrogel bead composition was optimized to achieve the highest swelling capacity, greatest erythrocyte adhesion, and minimal in vitro cytotoxicity. These results suggest a polymer hydrogel-aluminosilicate composite material may serve as a platform for an effective hemostatic agent that incorporates multiple mechanisms of action.