@article{roosa_muhamed_young_nellenbach_daniele_ligler_brown_2021, title={Synthesis of sonicated fibrin nanoparticles that modulate fibrin clot polymerization and enhance angiogenic responses}, volume={204}, ISSN={["1873-4367"]}, DOI={10.1016/j.colsurfb.2021.111805}, abstractNote={Chronic wounds can occur when the healing process is disrupted and the wound remains in a prolonged inflammatory stage that leads to severe tissue damage and poor healing outcomes. Clinically used treatments, such as high density, FDA-approved fibrin sealants, do not provide an optimal environment for native cell proliferation and subsequent tissue regeneration. Therefore, new treatments outside the confines of these conventional fibrin bulk gel therapies are required. We have previously developed flowable, low-density fibrin nanoparticles that, when coupled to keratinocyte growth factor, promote cell migration and epithelial wound closure in vivo. Here, we report a new high throughput method for generating the fibrin nanoparticles using probe sonication, which is less time intensive than the previously reported microfluidic method, and investigate the ability of the sonicated fibrin nanoparticles (SFBN) to promote clot formation and cell migration in vitro. The SFBNs can form a fibrin gel when combined with fibrinogen in the absence of exogenous thrombin, and the polymerization rate and fiber density in these fibrin clots is tunable based on SFBN concentration. Furthermore, fibrin gels made with SFBNs support cell migration in an in vitro angiogenic sprouting assay, which is relevant for wound healing. In this report, we show that SFBNs may be a promising wound healing therapy that can be easily produced and delivered in a flowable formulation.}, journal={COLLOIDS AND SURFACES B-BIOINTERFACES}, author={Roosa, Colleen A. and Muhamed, Ismaeel and Young, Ashlyn T. and Nellenbach, Kimberly and Daniele, Michael A. and Ligler, Frances S. and Brown, Ashley C.}, year={2021}, month={Aug} }
 @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"]}, 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}, author={Muhamed, Ismaeel and Sproul, Erin P. and Ligler, Frances S. and Brown, Ashley C.}, year={2019}, month={Jan}, pages={3771–3780} }