@article{prodromou_moore_chu_deal_san miguel_brown_daniele_pozdin_menegatti_2023, title={Molecular Engineering of Cyclic Azobenzene-Peptide Hybrid Ligands for the Purification of Human Blood Factor VIII via Photo-Affinity Chromatography}, volume={1}, ISSN={["1616-3028"]}, DOI={10.1002/adfm.202213881}, abstractNote={The use of benign stimuli to control the binding and release of labile biologics for their isolation from complex feedstocks is a key goal of modern biopharmaceutical technology. This study introduces cyclic azobenzene-peptide (CAP) ligands for the rapid and discrete photo-responsive capture and release of blood coagulation factor VIII (FVIII). A predictive method—based on amino acid sequence and molecular architecture of CAPs—is developed to correlate the conformation of cis/trans-CAP photo-isomers to FVIII binding and release. Combined in silico - in vitro analysis of FVIII:peptide interactions guide the design of a rational approach to optimize isomerization kinetics and biorecognition of CAPs. A photoaffinity adsorbent, prepared by conjugating selected CAP G-cycloAZOB[Lys-YYKHLYN-Lys]-G on translucent chromatographic beads, features high binding capacity (>6 mg of FVIII per mL of resin) and rapid photo-isomerization kinetics (τ < 30 s) when exposed to 420–450 nm light at the intensity of 0.1 W cm−2. The adsorbent purifies FVIII from a recombinant harvest using a single mobile phase, affording high product yield (>90%), purity (>95%), and blood clotting activity. The CAPs introduced in this report demonstrate a novel route integrating gentle operational conditions in a rapid and efficient bioprocess for the purification of life-saving biotherapeutics.}, journal={ADVANCED FUNCTIONAL MATERIALS}, author={Prodromou, Raphael and Moore, Brandyn David and Chu, Wenning and Deal, Halston and San Miguel, Adriana and Brown, Ashley Carson and Daniele, Michael Angelo-Anthony and Pozdin, Vladimir Aleksandrovich and Menegatti, Stefano}, year={2023}, month={Jan} }
 @article{mihalko_sandry_mininni_nellenbach_deal_daniele_ghadimi_levy_brown_2021, title={Fibrin-modulating nanogels for treatment of disseminated intravascular coagulation}, volume={5}, ISSN={["2473-9537"]}, DOI={10.1182/bloodadvances.2020003046}, abstractNote={Abstract Disseminated intravascular coagulation (DIC) is a pathological coagulopathy associated with infection that increases mortality. In DIC, excessive thrombin generation causes symptoms from formation of microthrombi to multiorgan failure; bleeding risks can also be a concern because of clotting factor consumption. Different clinical events lead to DIC, including sepsis, trauma, and shock. Treatments for thrombotic episodes or bleeding presentation in DIC oppose each other, thus creating therapeutic dilemmas in management. The objective of this study was to develop fibrin-specific core-shell nanogels (FSNs) loaded with tissue-type plasminogen activator (tPA) to treat the microcirculatory complications of DIC, which would facilitate targeted clot dissolution to manage microthrombi and the potential consumptive coagulopathy that causes bleeding. FSNs enhance formation of actively polymerizing clots by crosslinking fibrin fibers, but they can also target preexisting microthrombi and, when loaded with tPA, facilitate targeted delivery to lyse the microthrombi. We hypothesized that this dual action would simultaneously address bleeding and microthrombi with DIC to improve outcomes. In vivo, tPA-FSNs decreased the presentation of multiorgan microthrombi, recovered platelet counts, and improved bleeding outcomes in a DIC rodent model. When incorporated with human DIC patient plasma, tPA-FSNs restored clot structure and clot growth under flow. Together, these data demonstrate that a fibrinolytic agent loaded into fibrin-targeting nanogels could improve DIC outcomes.}, number={3}, journal={BLOOD ADVANCES}, author={Mihalko, Emily P. and Sandry, Megan and Mininni, Nicholas and Nellenbach, Kimberly and Deal, Halston and Daniele, Michael and Ghadimi, Kamrouz and Levy, Jerrold H. and Brown, Ashley C.}, year={2021}, month={Feb}, pages={613–627} }
 @article{petet_deal_zhao_he_tang_lemmon_2021, title={Rheological characterization of poly-dimethyl siloxane formulations with tunable viscoelastic properties}, volume={11}, ISSN={["2046-2069"]}, DOI={10.1039/d1ra03548g}, abstractNote={Studies from the past two decades have demonstrated convincingly that cells are able to sense the mechanical properties of their surroundings. Cells make major decisions in response to this mechanosensation, including decisions regarding cell migration, proliferation, survival, and differentiation. The vast majority of these studies have focused on the cellular mechanoresponse to changing substrate stiffness (or elastic modulus) and have been conducted on purely elastic substrates. In contrast, most soft tissues in the human body exhibit viscoelastic behavior; that is, they generate responsive force proportional to both the magnitude and rate of strain. While several recent studies have demonstrated that viscous effects of an underlying substrate affect cellular mechanoresponse, there is not a straightforward experimental method to probe this, particularly for investigators with little background in biomaterial fabrication. In the current work, we demonstrate that polymers comprised of differing polydimethylsiloxane (PDMS) formulations can be generated that allow for control over both the strain-dependent storage modulus and the strain rate-dependent loss modulus. These substrates requires no background in biomaterial fabrication to fabricate, are shelf-stable, and exhibit repeatable mechanical properties. Here we demonstrate that these substrates are biocompatible and exhibit similar protein adsorption characteristics regardless of mechanical properties. Finally, we develop a set of empirical equations that predicts the storage and loss modulus for a given blend of PDMS formulations, allowing users to tailor substrate mechanical properties to their specific needs.}, number={57}, journal={RSC ADVANCES}, author={Petet, Thomas J., Jr. and Deal, Halston E. and Zhao, Hanhsen S. and He, Amanda Y. and Tang, Christina and Lemmon, Christopher A.}, year={2021}, month={Nov}, pages={35910–35917} }
 @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={Native platelets are crucial players in wound healing. Key to their role is the ability of their surface receptor GPIIb/IIIa to bind fibrin at injury sites, thereby promoting clotting. When platelet activity is impaired as a result of traumatic injury or certain diseases, uncontrolled bleeding can result. To aid clotting and tissue repair in cases of poor platelet activity, our lab has previously developed synthetic platelet-like particles capable of promoting clotting and improving wound healing responses. These are constructed by functionalizing highly deformable hydrogel microparticles (microgels) with fibrin-binding ligands including a fibrin-specific whole antibody or a single-domain variable fragment. To improve the translational potential of these clotting materials, we explored the use of fibrin-binding peptides as cost-effective, robust, high-specificity alternatives to antibodies. Herein, we present the development and characterization of soft microgels decorated with the peptide AHRPYAAK that mimics fibrin knob 'B' and targets fibrin hole 'b'. These "Fibrin-Affine Microgels with Clotting Yield" (FAMCY) were found to significantly increase clot density in vitro and decrease bleeding in a rodent trauma model in vivo. These results indicate that FAMCYs are capable of recapitulating the platelet-mimetic properties of previous designs while utilizing a less costly, more translational design.}, 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} }
 @misc{deal_brown_daniele_2020, title={Microphysiological systems for the modeling of wound healing and evaluation of pro-healing therapies}, volume={8}, ISSN={["2050-7518"]}, DOI={10.1039/d0tb00544d}, abstractNote={Wound healing microphysiological systems have been engineered with synthetic and natural materials and techniques such as bioprinting or viscous finger patterning. Model designs focus on particular phases of wound healing or the recapitulation of micro-anatomies.}, number={32}, journal={JOURNAL OF MATERIALS CHEMISTRY B}, author={Deal, Halston E. and Brown, Ashley C. and Daniele, Michael A.}, year={2020}, month={Aug}, pages={7062–7075} }