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Biomimetic microgels with controllable deformability improve healing outcomes.

ABSTRACT: Platelets mediate hemostasis by aggregating and binding to fibrin to promote clotting. Over time, platelets contract the fibrin network to induce clot retraction, which contributes to wound healing outcomes by increasing clot stability and improving blood flow to ischemic tissue. In this study, we describe the development of hollow platelet-like particles (PLPs) that mimic the native platelet function of clot retraction in a controlled manner and demonstrate that clot retraction-inducing PLPs promote healing in vivo. PLPs are created by coupling fibrin-binding antibodies to CoreShell (CS) or hollow N-isopropylacrylamide (NIPAm) microgels with varying degrees of shell crosslinking. We demonstrate that hollow microgels with loosely crosslinked shells display a high degree of deformability and mimic activated platelet morphology, while intact CS microgels and hollow microgels with increased crosslinking in the shell do not. When coupled to a fibrin-binding antibody to create PLPs, hollow particles with low degrees of shell crosslinking cause fibrin clot collapse in vitro, recapitulating the clot retraction function of platelets, while other particle types do not. Furthermore, hollow PLPs with low degrees of shell crosslinking improve some wound healing outcomes in vivo.

SUBMITTER: Sproul EP

PROVIDER: S-EPMC7869964 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Biomimetic microgels with controllable deformability improve healing outcomes.

Sproul Erin P EP Nandi Seema S Roosa Colleen C Schreck Luisa L Brown Ashley C AC

Advanced biosystems 20180814 10

Platelets mediate hemostasis by aggregating and binding to fibrin to promote clotting. Over time, platelets contract the fibrin network to induce clot retraction, which contributes to wound healing outcomes by increasing clot stability and improving blood flow to ischemic tissue. In this study, we describe the development of hollow platelet-like particles (PLPs) that mimic the native platelet function of clot retraction in a controlled manner and demonstrate that clot retraction-inducing PLPs pr ...[more]

PMID: 33564714

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Project description:Microgels that can generate antipathogenic levels of hydrogen peroxide (H2O2) through simple rehydration in solutions with physiological pH are described herein. H2O2 is a widely used disinfectant but the oxidant is hazardous to store and transport. Catechol, an adhesive moiety found in mussel adhesive proteins, was incorporated into microgels, which generated 1-5 mM of H2O2 for up to four days as catechol autoxidized. The sustained release of low concentrations of H2O2 was antimicrobial against both gram-positive (Staphylococcus epidermidis) and gram-negative (Escherichia coli) bacteria and antiviral against both non-enveloped porcine parvovirus (PPV) and enveloped bovine viral diarrhea virus (BVDV). The amount of released H2O2 is several orders of magnitude lower than H2O2 concentration previously reported for antipathogenic activity. Most notably, these microgels reduced the infectivity of the more biocide resistant non-envelope virus by 3 log reduction value (99.9% reduction in infectivity). By controlling the oxidation state of catechol, microgels can be repeatedly activated and deactivated for H2O2 generation. These microgels do not contain a reservoir for storing the reactive H2O2 and can potentially function as a lightweight and portable dried powder source for the disinfectant for a wide range of applications. STATEMENT OF SIGNIFICANCE: Researchers have designed bioadhesives and coatings using the adhesive moiety catechol to mimic the strong adhesion capability of mussel adhesive proteins. During catechol autoxidation, hydrogen peroxide (H2O2) is generated as a byproduct. Here, catechol was incorporated into microgels, which can generate millimolar levels of H2O2 by simply hydrating the microgels in a solution with physiological pH. The sustained release of H2O2 was both antimicrobial and antiviral, inactivating even the more biocide resistant non-enveloped virus. These microgels can be repeatedly activated and deactivated for H2O2 generation by incubating them in solutions with different pH. This simplicity and recyclability will enable this biomaterial to function as a lightweight and portable source for the disinfectant for a wide range of applications.

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Biomimetic microgels with controllable deformability improve healing outcomes.

Publications

Biomimetic microgels with controllable deformability improve healing outcomes.

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