@article{ogunnaike_valdivia_yazdimamaghani_leon_nandi_hudson_du_khagi_gu_savoldo_et al._2021, title={Fibrin gel enhances the antitumor effects of chimeric antigen receptor T cells in glioblastoma}, volume={7}, ISSN={["2375-2548"]}, DOI={10.1126/sciadv.abg5841}, abstractNote={In situ fibrin gel promotes the survival and the biodistribution of CAR-T cells, eliminating residual GBM cells after surgery.}, number={41}, journal={SCIENCE ADVANCES}, author={Ogunnaike, Edikan A. and Valdivia, Alain and Yazdimamaghani, Mostafa and Leon, Ernesto and Nandi, Seema and Hudson, Hannah and Du, Hongwei and Khagi, Simon and Gu, Zhen and Savoldo, Barbara and et al.}, year={2021}, month={Oct} }
 @article{todd_bharadwaj_nellenbach_nandi_mihalko_copeland_brown_stabenfeldt_2021, title={Platelet-like particles reduce coagulopathy-related and neuroinflammatory pathologies post-experimental traumatic brain injury}, ISSN={["1552-4981"]}, DOI={10.1002/jbm.b.34888}, abstractNote={Abstract}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS}, author={Todd, Jordan and Bharadwaj, Vimala N. and Nellenbach, Kimberly and Nandi, Seema and Mihalko, Emily and Copeland, Connor and Brown, Ashley C. and Stabenfeldt, Sarah E.}, year={2021}, month={Jun} }
 @article{nandi_mihalko_nellenbach_castaneda_schneible_harp_deal_daniele_menegatti_barker_et al._2021, title={Synthetic Platelet Microgels Containing Fibrin Knob B Mimetic Motifs Enhance Clotting Responses}, volume={4}, ISSN={["2366-3987"]}, DOI={10.1002/adtp.202100010}, abstractNote={Abstract}, number={5}, journal={ADVANCED THERAPEUTICS}, author={Nandi, Seema and Mihalko, Emily and Nellenbach, Kimberly and Castaneda, Mario and Schneible, John and Harp, Mary and Deal, Halston and Daniele, Michael and Menegatti, Stefano and Barker, Thomas H. and et al.}, year={2021}, month={May} }
 @article{sproul_nandi_chee_sivadanam_igo_schreck_brown_2020, title={Development of Biomimetic Antimicrobial Platelet-Like Particles Comprised of Microgel Nanogold Composites}, volume={6}, ISSN={["2364-4141"]}, 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}, 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={2020}, month={Sep}, pages={299–309} }
 @article{chee_nandi_nellenbach_mihalko_snider_morrill_bond_sproul_sollinger_cruse_et al._2020, title={Nanosilver composite pNIPAm microgels for the development of antimicrobial platelet-like particles}, volume={108}, ISSN={["1552-4981"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85080073268&partnerID=MN8TOARS}, DOI={10.1002/jbm.b.34592}, abstractNote={Abstract}, number={6}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS}, author={Chee, Eunice and Nandi, Seema and Nellenbach, Kimberly and Mihalko, Emily and Snider, Douglas B. and Morrill, Landon and Bond, Andrew and Sproul, Erin and Sollinger, Jennifer and Cruse, Glenn and et al.}, year={2020}, month={Aug}, pages={2599–2609} }
 @article{nellenbach_nandi_peeler_kyu_brown_2020, title={Neonatal Fibrin Scaffolds Promote Enhanced Cell Adhesion, Migration, and Wound Healing In Vivo Compared to Adult Fibrin Scaffolds}, ISBN={1865-5033}, DOI={10.1007/s12195-020-00620-5}, abstractNote={Fibrin scaffolds are often utilized to treat chronic wounds. The monomer fibrinogen used to create such scaffolds is typically derived from adult human or porcine plasma. However, our previous studies have identified extensive differences in fibrin network properties between adults and neonates, including higher fiber alignment in neonatal networks. Wound healing outcomes have been linked to fibrin matrix structure, including fiber alignment, which can affect the binding and migration of cells. We hypothesized that fibrin scaffolds derived from neonatal fibrin would enhance wound healing outcomes compared to adult fibrin scaffolds.Fibrin scaffolds were formed from purified adult or neonatal fibrinogen and thrombin then structural analysis was conducted via confocal microscopy. Human neonatal dermal fibroblast attachment, migration, and morphology on fibrin scaffolds were assessed. A murine full thickness injury model was used to compare healing in vivo in the presence of neonatal fibrin, adult fibrin, or saline.Distinct fibrin architectures were observed between adult and neonatal scaffolds. Significantly higher fibroblast attachment and migration was observed on neonatal scaffolds compared to adults. Cell morphology on neonatal scaffolds exhibited higher spreading compared to adult scaffolds. In vivo significantly smaller wound areas and greater epidermal thickness were observed when wounds were treated with neonatal fibrin compared to adult fibrin or a saline control.Distinctions in neonatal and adult fibrin scaffold properties influence cellular behavior and wound healing. These studies indicate that fibrin scaffolds sourced from neonatal plasma could improve healing outcomes compared to scaffolds sourced from adult plasma.}, journal={CELLULAR AND MOLECULAR BIOENGINEERING}, author={Nellenbach, Kimberly and Nandi, Seema and Peeler, Christopher and Kyu, Alexander and Brown, Ashley C.}, year={2020} }
 @article{nandi_sommerville_nellenbach_mihalko_erb_freytes_hoffman_monroe_brown_2020, title={Platelet-like particles improve fibrin network properties in a hemophilic model of provisional matrix structural defects}, volume={577}, ISSN={["1095-7103"]}, DOI={10.1016/j.jcis.2020.05.088}, abstractNote={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.}, journal={JOURNAL OF COLLOID AND INTERFACE SCIENCE}, author={Nandi, Seema and Sommerville, Laura and Nellenbach, Kimberly and Mihalko, Emily and Erb, Mary and Freytes, Donald O. and Hoffman, Maureane and Monroe, Dougald and Brown, Ashley C.}, year={2020}, month={Oct}, pages={406–418} }
 @article{nandi_mohanty_nellenbach_erb_muller_brown_2020, title={Ultrasound Enhanced Synthetic Platelet Therapy for Augmented Wound Repair}, volume={6}, ISSN={["2373-9878"]}, DOI={10.1021/acsbiomaterials.9b01976}, abstractNote={Native platelets perform a number of functions within the wound healing process, including interacting with fibrin fibers at the wound site to bring about retraction after clot formation. Clot retraction improves clot stability and enhances the function of the fibrin network as a provisional matrix to support cellular infiltration of the wound site, thus facilitating tissue repair and remodeling after hemostasis. In cases of traumatic injury or disease, platelets can become depleted and this process disrupted. To that end, our lab has developed synthetic platelet-like particles (PLPs) that recapitulate the clot retraction abilities of native platelets through a Brownian-wrench driven mechanism that drives fibrin network densification and clot retraction over time, however, this Brownian-motion driven process occurs on a longer time scale than native active actin/myosin-driven platelet-mediated clot retraction. We hypothesized that a combinatorial therapy comprised of ultrasound stimulation of PLP motion within fibrin clots would facilitate a faster induction of clot retraction on a more platelet-mimetic time scale and at a lower dosage than required for PLPs acting alone. We found that application of ultrasound in combination with a subtherapeutic dosage of PLPs resulted in increased clot density and stiffness, improved fibroblast migration in vitro and increased epidermal thickness and angiogenesis in vivo, indicating that this combination therapy has potential to facilitate multiphase pro-healing outcomes. Additionally, while these particular studies focus on the role of ultrasound in enhancing specific interactions between fibrin-binding synthetic PLPs embedded within fibrin networks, these studies have wide applicability in understanding the role of ultrasound stimulation in enhancing multi-scale colloidal interactions within fibrillar matrices.}, number={5}, journal={ACS BIOMATERIALS SCIENCE & ENGINEERING}, author={Nandi, Seema and Mohanty, Kaustav and Nellenbach, Kimberly and Erb, Mary and Muller, Marie and Brown, Ashley C.}, year={2020}, month={May}, pages={3026–3036} }
 @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={["2047-4849"]}, DOI={10.1039/c8bm01201f}, abstractNote={PLPs increase fibrin stiffness, promote cell migration, and improve healing outcomes.}, number={2}, journal={BIOMATERIALS SCIENCE}, 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}, month={Feb}, pages={669–682} }
 @article{sproul_nandi_roosa_schreck_brown_2018, title={Biomimetic Microgels with Controllable Deformability Improve Healing Outcomes}, volume={2}, ISSN={["2366-7478"]}, DOI={10.1002/adbi.201800042}, abstractNote={Abstract}, number={10}, journal={ADVANCED BIOSYSTEMS}, author={Sproul, Erin P. and Nandi, Seema and Roosa, Colleen and Schreck, Luisa and Brown, Ashley C.}, year={2018}, month={Oct} }
 @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{joshi_nandi_chester_brown_muller_2018, title={Study of Poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM) Microgel Particle Induced Deformations of Tissue-Mimicking Phantom by Ultrasound Stimulation}, volume={34}, ISSN={["0743-7463"]}, DOI={10.1021/acs.langmuir.7b02801}, abstractNote={Poly(N-isopropylacrylamide) (pNIPAm) microgels (microgels) are colloidal particles that have been used extensively for biomedical applications. Typically, these particles are synthesized in the presence of an exogenous cross-linker, such as N,N'-methylenebis(acrylamide) (BIS); however, recent studies have demonstrated that pNIPAm microgels can be synthesized in the absence of an exogenous cross-linker, resulting in the formation of ultralow cross-linked (ULC) particles, which are highly deformable. Microgel deformability has been linked in certain cases to enhanced bioactivity when ULC microgels are used for the creation of biomimetic particles. We hypothesized that ultrasound stimulation of microgels would enhance particle deformation and that the degree of enhancement would negatively correlate with the degree of particle cross-linking. Here, we demonstrate in tissue-mimicking phantoms that using ultrasound insonification causes deformations of ULC microgel particles. Furthermore, the amount of deformation depends on the ultrasound excitation frequency and amplitude and on the concentration of ULC microgel particles. We observed that the amplitude of deformation increases with increasing ULC microgel particle concentration up to 2.5 mg/100 mL, but concentrations higher than 2.5 mg/100 mL result in reduced amount of deformation. In addition, we observed that the amplitude of deformation was significantly higher at 1 MHz insonification frequency. We also report that increasing the degree of microgel cross-linking reduces the magnitude of the deformation and increases the optimal concentration required to achieve the largest amount of deformation. Stimulated ULC microgel particle deformation has numerous potential biomedical applications, including enhancement of localized drug delivery and biomimetic activity. These results demonstrate the potential of ultrasound stimulation for such applications.}, number={4}, journal={LANGMUIR}, author={Joshi, Aditya and Nandi, Seema and Chester, Daniel and Brown, Ashley C. and Muller, Marie}, year={2018}, month={Jan}, pages={1457–1465} }
 @article{nandi_brown_2017, title={Characterizing Cell Migration Within Three-dimensional In Vitro Wound Environments}, ISSN={["1940-087X"]}, DOI={10.3791/56099}, abstractNote={Currently, most in vitro models of wound healing, such as well-established scratch assays, involve studying cell migration and wound closure on two-dimensional surfaces. However, the physiological environment in which in vivo wound healing takes place is three-dimensional rather than two-dimensional. It is becoming increasingly clear that cell behavior differs greatly in two-dimensional vs. three-dimensional environments; therefore, there is a need for more physiologically relevant in vitro models for studying cell migration behaviors in wound closure. The method described herein allows for the study of cell migration in a three-dimensional model that better reflects physiological conditions than previously established two-dimensional scratch assays. The purpose of this model is to evaluate cell outgrowth via the examination of cell migration away from a spheroid body embedded within a fibrin matrix in the presence of pro- or anti-migratory factors. Using this method, cell outgrowth from the spheroid body in a three-dimensional matrix can be observed and is easily quantifiable over time via brightfield microscopy and analysis of spheroid body area. The effect of pro-migratory and/or inhibitory factors on cell migration can also be evaluated in this system. This method provides researchers with a simple method of analyzing cell migration in three-dimensional wound associated matrices in vitro, thus increasing the relevance of in vitro cell studies prior to the use of in vivo animal models.}, number={126}, journal={JOVE-JOURNAL OF VISUALIZED EXPERIMENTS}, author={Nandi, Seema and Brown, Ashley C.}, year={2017}, month={Aug} }