Development of a Nonwoven Hemostatic Dressing Based on Unbleached Cotton: a De Novo Design Approach
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pharmaceutics Article Development of a Nonwoven Hemostatic Dressing Based on Unbleached Cotton: A De Novo Design Approach J. Vincent Edwards 1,*, Elena Graves 1, Nicolette Prevost 1, Brian Condon 1, Dorne Yager 2, Joseph Dacorta 3 and Alvin Bopp 4 1 Southern Regional Research Center, New Orleans, LA 70124, USA; [email protected] (E.G.); [email protected] (N.P.); [email protected] (B.C.) 2 Plastic and Reconstructive Surgery, Virginia Commonwealth University, Richmond, VA 23111, USA; [email protected] 3 H&H Medical Corporation, Williamsburg, VA 23185, USA; [email protected] 4 Department of Natural Sciences, Southern University at New Orleans, New Orleans, LA 70126, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-504-284-4360 Received: 30 January 2020; Accepted: 22 June 2020; Published: 30 June 2020 Abstract: Minimally processed greige (unbleached) cotton fibers demonstrate enhanced clotting relative to highly processed United States Pharmacopeia (USP) type 7 bleached cotton gauze. This effect is thought to be due to the material surface polarity. We hypothesized that a textile could be constructed, conserving the hemostasis-accelerating properties of greige cotton, while maintaining structural integrity and improving absorbance. Spun bond nonwovens of varying surface polarity were designed and prepared based on ratios of greige cotton/bleached cotton/polypropylene fibers. A thromboelastographic analysis was performed on fibrous samples in citrated blood to evaluate the rate of fibrin and clot formation. Lee White clotting times were obtained to assess the material’s clotting activity in platelet fresh blood. An electrokinetic analysis of samples was performed to analyze for material surface polarity. Hemostatic properties varied with composition ratios, fiber density, and fabric fenestration. The determinations of the surface polarity of cotton fabrics with electrokinetic analysis uncovered a range of surface polarities implicated in fabric-initiated clotting; a three-point design approach was employed with the combined use of thromboelastography, thrombin velocity index, Lee White clotting, and absorption capacity determinations applied to fabric structure versus function analysis. The resulting analysis demonstrates that greige cotton may be utilized, along with hydrophilic and hydrophobic fibers, to improve the initiation of fibrin formation and a decrease in clotting time in hemostatic dressings suitable to be commercially developed. Hydroentanglement is an efficient and effective process for imparting structural integrity to cotton-based textiles, while conserving hemostatic function. Keywords: cotton; blood clotting; thromboelastography; nonwovens; electrokinetic; fibrin; thrombin; platelets 1. Introduction Cotton has been a dressing staple for wound tamponade establishment for centuries. With the exception of its use in historically high demand periods, as in the ancient times of battle and the American Civil War, greige unbleached cotton has been relatively unexplored with regard to hemostatic dressing applications [1,2]. Nonwoven materials utilizing traditional fibers, such as bleached cotton, rayon and polyester, are utilized in hemostatic gauze. Due to innovations in cleaning and hydroentanglement, Pharmaceutics 2020, 12, 609; doi:10.3390/pharmaceutics12070609 www.mdpi.com/journal/pharmaceutics PharmaceuticsPharmaceutics2020 2020, ,12 12,, 609 x 22 of of 19 19 and hydroentanglement, there is growing interest in the potential use of greige cotton in nonwoven theredressings is growing [3,4]. interestAs shown in the in potentialFigure 1, use the of greigecotton cottonfiber consists in nonwoven of an dressings outer protective [3,4]. As showncuticle, incontaining Figure1, thehydrophobic cotton fiber lipids consists that ofare an only outer a protectivefew percent cuticle, by the containing weight of hydrophobic the total fiber lipids [3]. thatNonwoven are only unbleached a few percent cotton by the retains weight the of thecuticle total fiberlipids, [3 ].which Nonwoven confer unbleacheda hydrophobic cotton character retains thepresented cuticle lipids,as a thin which waxy confer layer aacross hydrophobic the fiber charactersurface. The presented lipid-containing as a thin waxylayer is layer loosened across from the fiberthe cellulosic surface. The primary lipid-containing cell wall during layer is loosenedthe hydroentanglement from the cellulosic process, primary and cell thus, wall exposes during thethe hydroentanglementcellulosic secondary process, cell wall. and It thus,is the exposeshydrophilic the cellulosic cellulosic secondary portion of cell the wall. cotton It isfibers the hydrophilicthat confers cellulosicwettability portion and absorbency. of the cotton The fibers combination that confers of a wettability hydrophobic and and absorbency. hydrophilic The character combination (termed of aamphiphilicity) hydrophobic and in hydroentangled hydrophilic character greige (termedcotton ma amphiphilicity)terials confers a in fluid hydroentangled management greige property cotton that materialshas functionality confers aas fluid a skin-contacting management property material, that as is has found functionality with hygienic as a skin-contacting top sheets and material, wound asdressings is found [4,5]. with These hygienic same top proper sheetsties and may wound make greige dressings cotton [4,5 ideally]. These suited same as properties a hemostatic may material make greigefor dressing cotton development. ideally suited as a hemostatic material for dressing development. FigureFigure 1. 1. AA montagemontage ofof cotton fiberfiber sections constructed fromfrom individualindividual electronelectron micrographsmicrographs (TEMs)(TEMs) andand scanningscanning micrographsmicrographs (SEMs)(SEMs) ofof thethe fiber.fiber. GivesGives anan overviewoverview ofof thethe layeredlayered structuresstructures ofof thethe fiber.fiber. The The fiber fiber cuticle, cuticle,primary primaryand and secondarysecondary cellcell wallswalls havehave beenbeen shownshown atat didifferentfferent magnifications,magnifications, toto better better visualize visualize fibrillary fibrillary structures structures and and fiber fiber layers layers from from the the surface surface to to the the lumen lumen [3 [3].]. MostMost of of the the current current literature literature tends tends to characterize to characterize hemostatic hemostatic textile-based textile-based materials asmaterials addressing as hemorrhageaddressing hemorrhage control. However, control. a However, broader measure a broader of measure hemostatic of hemostatic material types material applies types to dressingsapplies to thatdressings accelerate that surfaceaccelerate hemostasis, surface hemostasis, and categorically and ca aretegorically either untreated are either or untreated treated textile or treated or granular textile materialsor granular [6– materials8]. Treated [6–8]. dressings Treated are dressings typically are woven typically or woven nonwoven or nonwoven textile materials textile materials that have that a hemostatichave a hemostatic agent incorporated, agent incorporated, i.e., clay i.e., minerals, clay minerals, chitosan chitosan (used singularly (used singularly as a fiber as or a coating), fiber or modifiedcoating), polysaccharidesmodified polysaccharides and/or fibrin and/or sealant fibrin as seal theant active as the clotting active clotting agent [6 agent]. Moreover, [6]. Moreover, these typesthese oftypes dressings, of dressings, which containwhich contain hemostasis-activating hemostasis-activating agents, agents, have been have classified been classified as either as factoreither concentrators,factor concentrators, pro-coagulants, pro-coagulants, or mucoadhesives, or mucoadhesives, based on theirbased mechanism on their mechanism of action to of initiate action and to sustaininitiate blood and sustain coagulation blood [ 7coagulation,8]. On the other[7,8]. hand,On the dressings other hand, which dressings demonstrate which a demonstrate degree of hemostatic a degree activityof hemostatic based onactivity de novo based design on de of novo woven design or nonwoven of woven or textiles nonwoven have beentextiles developed have been from developed single orfrom multiple single fiberor multiple blends fiber [9]. Inblends this case,[9]. In the this structure case, the/function structure/function relationship relationship of fiber and of materialfiber and designmaterial often design varies, often based varies, on surface based area, on charge,surface polarity, area, charge, surface morphology,polarity, surface the material’s morphology, porosity, the wickingmaterial’s function porosity, and wicking absorption function capacity, and which absorption are related capacity, directly which to in are vivo relatedmodels, directly i.e., assessments to in vivo donemodels, animal i.e., hemostasisassessments models. done animal hemostasis models. DespiteDespite thethe largelarge numbernumber ofof dressingsdressings usedused for for hemostasis, hemostasis, fewfew reports reports havehave comprehensively comprehensively evaluatedevaluated thethe eeffectffect ofof materialmaterial propertiesproperties asas separateseparate andand causativecausative eeffectsffects betweenbetween andand withinwithin interrelatedinterrelated fiberfiber andand fabricfabric structural structural features. features. ApproachesApproaches toto evaluatingevaluating thethe structurestructure/function/function relationsrelations ofof materials materials for for hemostatic hemostatic