Nanosilver composite pNIPAm microgels for the development of antimicrobial platelet‐like particles

Chee, Eunice; Nandi, Sisir; Nellenbach, Kimberly; Mihalko, Emily; Snider, Douglas B.; Morrill, Landon; Bond, Andrew D.; Sproul, Erin P.; Sollinger, Jennifer; Cruse, Glenn; Hoffman, Maureane; Brown, Ashley

doi:10.1002/jbm.b.34592

Cited by 13 publications

(14 citation statements)

References 23 publications

(30 reference statements)

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“…Previous studies have shown that, when incorporated into in vivo wounds, PLPs incorporate with native fibrin forming at wound sites [33]. In a separate set of studies investigating nanosilver composite PLPs in an infected wound model, we did not observe particles in histological sections 9 days post-injury [50], indicating that PLPs are cleared when applied topically; however, detailed studies into the eventual clearance mechanism of PLPs in this application have not yet been performed.…”

Section: Clot Density and Fibroblast Migration Are Enhanced In The Presence Of Plps Within A Platelet-rich Environmentmentioning

confidence: 57%

“…It is also possible that the effect of adding PLPs under this condition are less pronounced than in the hemophilialike condition due to the vastly greater force exerted by native platelets within a clot matrix relative to those exerted by PLPs [33,46]. Nonetheless, in our previous studies investigating the role of PLPs on wound healing outcomes in vivo in a rodent full thickness dermal, we observed significant enhancement when PLPs were applied to the wound, even though this was a healthy model [33,50] with functional platelets, which is likely due to the early influence that PLPs have on network. In these experiments, we found PLPs did not significantly increase clot density in the presence of platelets under normal, healthy conditions; this is likely due to the fact that native platelets act on a faster time scale than PLPs do within fibrin networks [33,46].…”

Section: Clot Density and Fibroblast Migration Are Enhanced In The Presence Of Plps Within A Platelet-rich Environmentmentioning

confidence: 81%

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Platelet-like particles improve fibrin network properties in a hemophilic model of provisional matrix structural defects

Nandi

Sommerville

Nellenbach

et al. 2020

Journal of Colloid and Interface Science

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Following injury, a fibrin-rich provisional matrix is formed to stem blood loss and provide a scaffold for infiltrating cells, which rebuild the damaged tissue. Defects in fibrin network formation contribute to impaired healing outcomes, as evidenced in hemophilia. Platelet-fibrin interactions greatly influence fibrin network structure via clot contraction, which increases fibrin density over time. Previously developed hemostatic platelet-like particles (PLPs) are capable of mimicking platelet functions including binding to fibrin fibers, augmenting clotting, and inducing clot retraction. In this study, we aimed to apply PLPs within a plasma-based in vitro hemophilia B model of deficient fibrin network structure to determine the ability of PLPs to improve fibrin structure and wound healing responses within hemophilia-like abnormal fibrin network formation. PLP impact on structurally deficient clot networks was assessed via confocal microscopy, a micropost deflection model, atomic force microscopy and an in vitro wound healing model of early cell migration within a provisional fibrin matrix. PLPs improved clot network density, force generation, and stiffness, and promoted fibroblast migration within an in vitro model of early wound healing under hemophilic conditions, indicating that PLPs could provide a biomimetic platform for improving wound healing events in disease conditions that cause deficient fibrin network formation.

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Section: Clot Density and Fibroblast Migration Are Enhanced In The Presence Of Plps Within A Platelet-rich Environmentmentioning

confidence: 57%

Section: Clot Density and Fibroblast Migration Are Enhanced In The Presence Of Plps Within A Platelet-rich Environmentmentioning

confidence: 81%

Platelet-like particles improve fibrin network properties in a hemophilic model of provisional matrix structural defects

Nandi

Sommerville

Nellenbach

et al. 2020

Journal of Colloid and Interface Science

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“…Total blood loss quantification over the course of the 10 min injury showed significantly lower total blood loss for animals that received treatment with 15 mg kg −1 FAMCYs (0.0078 ± 0.003 gram blood/gram animal) compared to saline treated animals (0.016 ± 0.004 gram blood/gram animal, p ‐value = 0.0193) (Figure 7). Furthermore, evaluation of total blood loss in animals receiving 15 mg kg −1 FAMCY treatment versus previously published data in total blood loss in animals receiving treatment with previous iterations of platelet‐mimetic particles that utilize either an antibody‐based [ 29 ] or sdFv‐based [ 25 ] targeting motif indicates that FAMCY formulations reduce overall blood loss similarly (≈50%–60% reduction relative to saline controls) to these previous formulations. Minimal differences in total blood loss were seen when comparing saline treatment to bare ULC microgel (0.012 ± 0.004 gram blood/gram animal, p ‐value = 0.7195) and control peptide FAMCYs (0.013 ± 0.002 gram blood/gram animal, p ‐value = 0.8178).…”

Section: Resultsmentioning

confidence: 90%

Synthetic Platelet Microgels Containing Fibrin Knob B Mimetic Motifs Enhance Clotting Responses

Nandi

Mihalko

Nellenbach

et al. 2021

Advanced Therapeutics

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Native platelets are crucial players in wound healing. Key to their role is the ability of their surface receptor GPIIb/IIIa to bind fibrin at injury sites, thereby promoting clotting. When platelet activity is impaired as a result of traumatic injury or certain diseases, uncontrolled bleeding can result. To aid clotting and tissue repair in cases of poor platelet activity, synthetic platelet‐like particles capable of promoting clotting and improving wound healing responses have been previously developed in the lab. These are constructed by functionalizing highly deformable hydrogel microparticles (microgels) with fibrin‐binding ligands including a fibrin‐specific whole antibody or a single‐domain variable fragment. To improve the translational potential of these clotting materials, the use of fibrin‐binding peptides as cost‐effective, robust, high‐specificity alternatives to antibodies are explored. Herein, the development and characterization of soft microgels decorated with the peptide AHRPYAAK that mimics fibrin knob “B” and targets fibrin hole “b” are presented. These “fibrin‐affine microgels with clotting yield” (FAMCY) are found to significantly increase clot density in vitro and decrease bleeding in a rodent trauma model in vivo. These results indicate that FAMCYs are capable of recapitulating the platelet‐mimetic properties of previous designs while utilizing a less costly, more translational design.

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“…Chee et al incorporated AgNPs within ultra-soft PNIPAm-based platelet-like microgels to mitigate bacterial growth during clot retraction, achieving a wound cloture rate compared to native PLPs and inhibiting microbial proliferation. [6] Uhlig et al incorporated carboxylated PS nanobeads within PNIPAm microgels coated onto glass coverslips and observed enhanced cell adhesion as the carboxylic acid moieties increased the hydrophilicity of the surface. [49] Microgels may also be used to mediate the formation of nanoparticle patterns onto surfaces.…”

Section: Nanoparticle Additionmentioning

confidence: 99%

“…The past two decades have witnessed a rapid increase in the use of hydrogel microparticles (henceforth, "microgels") as surface coatings for advancing filtration, [1][2][3][4] wound dressing, [5][6][7][8] sensing, [9][10][11][12][13] antifouling, [14][15][16] sequestration of chemicals, [17] and controlled delivery applications. [18][19][20][21] The versatility of microgelbased coatings stems from the physicochemical and morphological properties of both microgels and surfaces, the deposition methods, and post-deposition treatments.…”

Section: Introductionmentioning

confidence: 99%

Surface‐Bound Microgels for Separation, Sensing, and Biomedical Applications

Cutright

Harris

Ramesh

et al. 2021

Adv Funct Materials

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This study presents a comprehensive survey of microgel-coated materials and their functional behavior, describing the complex interplay between the physicochemical and mechanical properties of the microgels and the chemical and morphological features of substrates. The cited literature is articulated in four main sections: i) properties of 2D and 3D substrates, ii) synthesis, modification, and characterization of the microgels, iii) deposition techniques and surface patterning, and iv) application of microgel-coated surfaces focusing on separations, sensing, and biomedical applications. Each section discussesby way of principles and examples -how the various design parameters work in concert to deliver functionality to the composite systems. The case studies presented herein are viewed through a multi-scale lens. At the molecular level, the surface chemistry and the monomer make-up of the microgels endow responsiveness to environmental and artificial physical and chemical cues. At the micro-scale, the response effects shifts in size, mechanical, and optical properties, and affinity towards species in the surrounding liquid medium, ranging from small molecules to cells. These phenomena culminate at the macro-scale in measurable, reversible, and reproducible effects, aiming in a myriad of directions, from lab-scale to industrial applications.

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Nanosilver composite pNIPAm microgels for the development of antimicrobial platelet‐like particles

Abstract: This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 13 publications

References 23 publications

Platelet-like particles improve fibrin network properties in a hemophilic model of provisional matrix structural defects

Platelet-like particles improve fibrin network properties in a hemophilic model of provisional matrix structural defects

Synthetic Platelet Microgels Containing Fibrin Knob B Mimetic Motifs Enhance Clotting Responses

Surface‐Bound Microgels for Separation, Sensing, and Biomedical Applications

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