@article{sproul_nandi_chee_sivadanam_igo_schreck_brown_2019, title={Development of Biomimetic Antimicrobial Platelet-Like Particles Comprised of Microgel Nanogold Composites}, volume={6}, ISSN={2364-4133 2364-4141}, url={http://dx.doi.org/10.1007/s40883-019-00121-6}, DOI={10.1007/s40883-019-00121-6}, abstractNote={A blood clot is formed in response to bleeding by platelet aggregation and adherence to fibrin fibers. Platelets contract over time, stabilizing the clot, which contributes to wound healing. We have developed platelet-like particles (PLPs) that augment clotting and induce clot retraction by mimicking the fibrin-binding capabilities and morphology of native platelets. Wound repair following hemostasis can be complicated by infection; therefore, we aim to augment wound healing by combining PLPs with antimicrobial gold to develop nanogold composites (NGCs). PLPs were synthesized with N-isopropylacrylamide (NIPAm)/co-acrylic acid in a precipitation polymerization reaction and conjugated to a fibrin-specific antibody. Two methods were employed to create NGCs: (1) noncovalent swelling with aqueous gold nanospheres, and (2) covalent seeding and growth. Since the ability of PLPs to mimic platelet morphology and clot retraction requires a high degree of particle deformability, we investigated how PLPs created from NGCs affected these properties. Cryogenic scanning electron microscopy (cryoSEM) and atomic force microscopy (AFM) demonstrated that particle deformability, platelet-mimetic morphology, and clot retraction were maintained in NGC-based PLPs. The effect of NGCs on bacterial adhesion and growth was assessed with antimicrobial assays. These results demonstrate NGCs fabricated through noncovalent and covalent methods retain deformability necessary for clot collapse and exhibit some antimicrobial potential. Therefore, NGCs are promising materials for preventing hemorrhage and infection following trauma. Following injury, a blood clot is formed by platelets aggregating and binding to fibrin fibers. Platelets contract over time, stabilizing the clot, which contributes to wound healing. We have developed PLPs that enhance clotting and stimulate clot retraction by mimicking the fibrin-binding capabilities and morphology of native platelets. Wound repair following hemostasis can be complicated by infection; therefore, we aim to amplify wound healing by combining PLPs with antimicrobial gold to develop NGCs. These NGC PLPs mimic platelet morphology, generate clot retraction, demonstrate some antimicrobial potential, and are promising materials for preventing blood loss and infection following trauma. Future work will include exploring the application of these particles to treat hemorrhage and infection following traumatic injury.}, number={3}, journal={Regenerative Engineering and Translational Medicine}, publisher={Springer Science and Business Media LLC}, author={Sproul, Erin P. and Nandi, Seema and Chee, Eunice and Sivadanam, Supriya and Igo, Benjamin J. and Schreck, Luisa and Brown, Ashley C.}, year={2019}, month={Aug}, pages={299–309} } @article{muhamed_sproul_ligler_brown_2019, title={Fibrin Nanoparticles Coupled with Keratinocyte Growth Factor Enhance the Dermal Wound-Healing Rate}, volume={11}, ISSN={1944-8244 1944-8252}, url={http://dx.doi.org/10.1021/acsami.8b21056}, DOI={10.1021/acsami.8b21056}, abstractNote={Expediting the wound-healing process is critical for patients chronically ill from nonhealing wounds and diseases such as hemophilia or diabetes or who have suffered trauma including easily infected open wounds. FDA-approved external tissue sealants include the topical application of fibrin gels, which can be 500 times denser than natural fibrin clots. With lower clot porosity and higher polymerization rates than physiologically formed fibrin clots, the commercial gels quickly stop blood loss but impede the later clot degradation kinetics and thus retard tissue-healing rates. The fibrin nanoparticles (FBNs) described here are constructed from physiologically relevant fibrin concentrations that support new tissue and dermal wound scaffold formation when coupled with growth factors. The FBNs, synthesized in a microfluidic droplet generator, support cell adhesion and traction generation, and when coupled to keratinocyte growth factor (KGF), support cell migration and in vivo wound healing. The FBN-KGF particles enhance cell migration in vitro greater than FBN alone or free KGF and also improve healing outcomes in a murine full thickness injury model compared to saline, bulk fibrin sealant, free KGF, or bulk fibrin mixed with KGF treatments. Furthermore, FBN can be potentially administered with other tissue-healing factors and inflammatory mediators to improve wound-healing outcomes.}, number={4}, journal={ACS Applied Materials & Interfaces}, publisher={American Chemical Society (ACS)}, author={Muhamed, Ismaeel and Sproul, Erin P. and Ligler, Frances S. and Brown, Ashley C.}, year={2019}, month={Jan}, pages={3771–3780} } @article{nandi_sproul_nellenbach_erb_gaffney_freytes_brown_2019, title={Platelet-like particles dynamically stiffen fibrin matrices and improve wound healing outcomes}, volume={7}, ISSN={2047-4830 2047-4849}, url={http://dx.doi.org/10.1039/C8BM01201F}, DOI={10.1039/c8bm01201f}, abstractNote={PLPs increase fibrin stiffness, promote cell migration, and improve healing outcomes.}, number={2}, journal={Biomaterials Science}, publisher={Royal Society of Chemistry (RSC)}, author={Nandi, Seema and Sproul, Erin P. and Nellenbach, Kimberly and Erb, Mary and Gaffney, Lewis and Freytes, Donald O. and Brown, Ashley C.}, year={2019}, pages={669–682} } @article{sproul_nandi_brown_2018, title={Fibrin biomaterials for tissue regeneration and repair}, ISBN={["978-0-08-100803-4"]}, ISSN={["2049-9485"]}, DOI={10.1016/b978-0-08-100803-4.00006-1}, abstractNote={Fibrin is an integral part of the clotting cascade and is formed by polymerization of the soluble plasma protein fibrinogen. Following the stimulation of the coagulation cascade, thrombin activates fibrinogen, which binds to adjacent fibrin(ogen) molecules resulting in the formation of an insoluble fibrin matrix. This fibrin network is the primary protein component in clots and subsequently provides a scaffold for infiltrating cells during tissue repair. Due to its role in hemostasis and tissue repair, fibrin has been used extensively as a tissue sealant. This chapter first provides an overview of the structure and function of fibrin(ogen) and details the role of fibrin-cell interactions in wound repair. The design and use of fibrin-based materials for promoting tissue repair is also discussed.}, journal={PEPTIDES AND PROTEINS AS BIOMATERIALS FOR TISSUE REGENERATION AND REPAIR}, author={Sproul, E. and Nandi, S. and Brown, A.}, year={2018}, pages={151–173} } @article{tang_su_huang_dinh_wang_vandergriff_hensley_cores_allen_li_et al._2018, title={Targeted repair of heart injury by stem cells fused with platelet nanovesicles}, volume={2}, ISSN={2157-846X}, url={http://dx.doi.org/10.1038/s41551-017-0182-x}, DOI={10.1038/s41551-017-0182-x}, abstractNote={Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites. We also find that the modified CSCs selectively bind collagen-coated surfaces and endothelium-denuded rat aortas, and that in rat and porcine models of acute myocardial infarction the modified CSCs increase retention in the heart and reduce infarct size. Platelet-nanovesicle-fused CSCs thus possess the natural targeting and repairing ability of their parental cell types. This stem cell manipulation approach is fast, straightforward and safe, does not require genetic alteration of the cells, and should be generalizable to multiple cell types. The attachment of platelet nanovesicles to the surface of cardiac stem cells increases the retention of the cells delivered to the heart and reduces infarct size in rat and pig models of acute myocardial infarction.}, number={1}, journal={Nature Biomedical Engineering}, publisher={Springer Science and Business Media LLC}, author={Tang, Junnan and Su, Teng and Huang, Ke and Dinh, Phuong-Uyen and Wang, Zegen and Vandergriff, Adam and Hensley, Michael T. and Cores, Jhon and Allen, Tyler and Li, Taosheng and et al.}, year={2018}, month={Jan}, pages={17–26} }