Platelet-like particles dynamically stiffen fibrin matrices and improve wound healing outcomes
Autor: | Mary Erb, Donald O. Freytes, Ashley C. Brown, Erin P. Sproul, Seema Nandi, Lewis Gaffney, Kimberly Nellenbach |
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Rok vydání: | 2019 |
Předmět: |
Blood Platelets
Biomedical Engineering Context (language use) 02 engineering and technology Clot retraction 010402 general chemistry 01 natural sciences Article Fibrin Fibroblast migration Mice Biomimetic Materials Animals Humans Medicine General Materials Science Platelet Mechanical Phenomena Skin Wound Healing biology business.industry Cell migration Platelet Activation 021001 nanoscience & nanotechnology 0104 chemical sciences Cell biology Hemostasis biology.protein 0210 nano-technology Wound healing business |
Zdroj: | Biomaterials Science. 7:669-682 |
ISSN: | 2047-4849 2047-4830 |
Popis: | Native platelets perform several critical functions within the context of wound healing, including participating in initial hemostasis and interacting with fibrin at the wound site to induce clot retraction. Platelet depletion or dysfunction due to trauma or disease can inhibit robust wound healing responses. There has been a focus recently on developing synthetic, non-immunogenic platelet mimetic technologies for the purpose of augmenting hemostatic responses in cases of deficient native platelet functionality. Here we describe the application of synthetic platelet-like particles (PLPs), capable of recapitulating the deformable platelet body and fibrin specificity found in native platelets, to enhance healing outcomes. We first demonstrate PLPs mimic activated platelet morphology and induce fibrin clot retraction. During clot retraction, native platelets generate forces within a fibrin network to stiffen the fibrin matrix; therefore, we hypothesized that our PLPs will likewise be able to stiffen provisional fibrin matrices. Due to previous studies indicating that increased matrix stiffness is linked to increased cellular migration, we further hypothesize that PLP-mediated fibrin stiffening will enhance cell migration and improve healing outcomes within in vitro and in vivo models of wound healing. PLPs were found to enhance fibroblast migration in in vitro models of early wound healing and enhance healing outcomes in an in vivo murine model of wound healing. These studies demonstrate the utility of PLPs for enhancing wound repair and also provide insight into the role of native platelet-mediated clot retraction in wound healing. |
Databáze: | OpenAIRE |
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