@article{scull_aligwekwe_rey_koch_nellenbach_sheridan_pandit_sollinger_pierce_flick_et al._2024, title={Fighting fibrin with fibrin: Vancomycin delivery into coagulase-mediated Staphylococcus aureus biofilms via fibrin-based nanoparticle binding}, volume={6}, ISSN={["1552-4965"]}, DOI={10.1002/jbm.a.37760}, abstractNote={Abstract Staphylococcus aureus skin and soft tissue infection is a common ailment placing a large burden upon global healthcare infrastructure. These bacteria are growing increasingly recalcitrant to frontline antimicrobial therapeutics like vancomycin due to the prevalence of variant populations such as methicillin‐resistant and vancomycin‐resistant strains, and there is currently a dearth of novel antibiotics in production. Additionally, S. aureus has the capacity to hijack the host clotting machinery to generate fibrin‐based biofilms that confer protection from host antimicrobial mechanisms and antibiotic‐based therapies, enabling immune system evasion and significantly reducing antimicrobial efficacy. Emphasis is being placed on improving the effectiveness of therapeutics that are already commercially available through various means. Fibrin‐based nanoparticles (FBNs) were developed and found to interact with S. aureus through the clumping factor A (ClfA) fibrinogen receptor and directly integrate into the biofilm matrix. FBNs loaded with antimicrobials such as vancomycin enabled a targeted and sustained release of antibiotic that increased drug contact time and reduced the therapeutic dose required for eradicating the bacteria, both in vitro and in vivo. Collectively, these findings suggest that FBN‐antibiotic delivery may be a novel and potent therapeutic tool for the treatment of S. aureus biofilm infections.}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A}, author={Scull, Grant and Aligwekwe, Adrian and Rey, Ysabel and Koch, Drew and Nellenbach, Kimberly and Sheridan, Ana and Pandit, Sanika and Sollinger, Jennifer and Pierce, Joshua G. and Flick, Matthew J. and et al.}, year={2024}, month={Jun} } @article{nellenbach_mihalko_nandi_koch_shetty_moretti_sollinger_moiseiwitsch_sheridan_pandit_et al._2024, title={Ultrasoft platelet-like particles stop bleeding in rodent and porcine models of trauma}, volume={16}, ISSN={["1946-6242"]}, DOI={10.1126/scitranslmed.adi4490}, abstractNote={Uncontrolled bleeding after trauma represents a substantial clinical problem. The current standard of care to treat bleeding after trauma is transfusion of blood products including platelets; however, donated platelets have a short shelf life, are in limited supply, and carry immunogenicity and contamination risks. Consequently, there is a critical need to develop hemostatic platelet alternatives. To this end, we developed synthetic platelet-like particles (PLPs), formulated by functionalizing highly deformable microgel particles composed of ultralow cross-linked poly (N-isopropylacrylamide) with fibrin-binding ligands. The fibrin-binding ligand was designed to target to wound sites, and the cross-linking of fibrin polymers was designed to enhance clot formation. The ultralow cross-linking of the microgels allows the particles to undergo large shape changes that mimic platelet shape change after activation; when coupled to fibrin-binding ligands, this shape change facilitates clot retraction, which in turn can enhance clot stability and contribute to healing. Given these features, we hypothesized that synthetic PLPs could enhance clotting in trauma models and promote healing after clotting. We first assessed PLP activity in vitro and found that PLPs selectively bound fibrin and enhanced clot formation. In murine and porcine models of traumatic injury, PLPs reduced bleeding and facilitated healing of injured tissue in both prophylactic and immediate treatment settings. We determined through biodistribution experiments that PLPs were renally cleared, possibly enabled by ultrasoft particle properties. The performance of synthetic PLPs in the preclinical studies shown here supports future translational investigation of these hemostatic therapeutics in a trauma setting.}, number={742}, journal={SCIENCE TRANSLATIONAL MEDICINE}, author={Nellenbach, Kimberly and Mihalko, Emily and Nandi, Seema and Koch, Drew W. and Shetty, Jagathpala and Moretti, Leandro and Sollinger, Jennifer and Moiseiwitsch, Nina and Sheridan, Ana and Pandit, Sanika and et al.}, year={2024}, month={Apr} } @article{chee_mihalko_nellenbach_sollinger_huang_hon_pandit_cheng_brown_2023, title={Wound‐triggered shape change microgels for the development of enhanced biomimetic function platelet‐like particles}, volume={112}, ISSN={1549-3296 1552-4965}, url={http://dx.doi.org/10.1002/jbm.a.37625}, DOI={10.1002/jbm.a.37625}, abstractNote={Abstract}, number={4}, journal={Journal of Biomedical Materials Research Part A}, publisher={Wiley}, author={Chee, Eunice and Mihalko, Emily and Nellenbach, Kimberly and Sollinger, Jennifer and Huang, Ke and Hon, Mason and Pandit, Sanika and Cheng, Ke and Brown, Ashley}, year={2023}, month={Oct}, pages={613–624} } @article{mihalko_nellenbach_krishnakumar_moiseiwitsch_sollinger_cooley_brown_2021, title={Fibrin‐specific poly(N‐isopropylacrylamide) nanogels for targeted delivery of tissue‐type plasminogen activator to treat thrombotic complications are well tolerated in vivo}, volume={7}, ISSN={2380-6761 2380-6761}, url={http://dx.doi.org/10.1002/btm2.10277}, DOI={10.1002/btm2.10277}, abstractNote={Abstract}, number={2}, journal={Bioengineering & Translational Medicine}, publisher={Wiley}, author={Mihalko, Emily P. and Nellenbach, Kimberly and Krishnakumar, Manasi and Moiseiwitsch, Nina and Sollinger, Jennifer and Cooley, Brian C. and Brown, Ashley C.}, year={2021}, month={Dec} } @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={1552-4973 1552-4981}, url={http://dx.doi.org/10.1002/jbm.b.34592}, DOI={10.1002/jbm.b.34592}, abstractNote={Abstract}, number={6}, journal={Journal of Biomedical Materials Research Part B: Applied Biomaterials}, publisher={Wiley}, 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={Feb}, pages={2599–2609} } @article{adams_moody_sollinger_brudno_2019, title={Extracellular-Matrix-Anchored Click Motifs for Specific Tissue Targeting}, volume={17}, ISSN={1543-8384 1543-8392}, url={http://dx.doi.org/10.1021/acs.molpharmaceut.9b00589}, DOI={10.1021/acs.molpharmaceut.9b00589}, abstractNote={Local presentation of cancer drugs by injectable drug eluting depots reduces systemic side effects and improves efficacy. However, local depots deplete their drug stores and are difficult to introduce into stiff tissues, or organs, such as the brain, that can not accommodate increased pressure. We present a method for introducing targetable depots through injection of activated ester molecules into target tissues that react with and anchor themselves to local extracellular matrix (ECM) and subsequently capture systemically-administered small molecules through bioorthogonal click chemistry. A computational model of tissue anchoring depot formation and distribution was verified by histological analysis and confocal imaging of cleared tissues. ECM-anchored click groups do not elicit any noticeable local or systemic toxicity or immune response and specifically capture systemically-circulating molecules at intradermal, intratumoral, and intracranial sites for multiple months. Taken together, ECM-anchoring of click chemistry motifs is a promising approach to specific targeting of both small and large therapeutics, enabling repeated local presentation for cancer therapy and other diseases.}, number={2}, journal={Molecular Pharmaceutics}, publisher={American Chemical Society (ACS)}, author={Adams, Mary R. and Moody, Christopher T. and Sollinger, Jennifer L. and Brudno, Yevgeny}, year={2019}, month={Dec}, pages={392–403} } @article{thompson_sollinger_opara_adin_2018, title={Selective Osmotic Shock for Islet Isolation in the Cadaveric Canine Pancreas}, volume={27}, ISSN={["1555-3892"]}, DOI={10.1177/0963689717752947}, abstractNote={ Currently, islet isolation is performed using harsh collagenases that cause nonspecific injury to both islets and exocrine tissue, negatively affecting the outcome of cell transplantation. We evaluated a novel islet isolation protocol utilizing high concentrations of glucose to cause selective osmotic shock (SOS). Islets have a membrane glucose transporter that allows adaptation to changes in glucose concentrations while exocrine tissue can be selectively destroyed by these osmolar shifts. Canine pancreata were obtained within 15 min after euthanasia from animals ( n = 6) euthanized for reasons unrelated to this study. Each pancreas was divided into 4 segments that were randomized to receive 300 mOsm glucose for 20 min (group 1), 600 mOsm for 20 min (group 2), 300 mOsm for 40 min (group 3), or 600 mOsm for 40 min (group 4). Islet yield, purity, and viability were compared between groups. Mean ± standard error of the mean islet yield for groups 1 to 4 was 428 ± 159, 560 ± 257, 878 ± 443, and 990 ± 394 islet equivalents per gram, respectively. Purity ranged from 37% to 45% without the use of density gradient centrifugation and was not significantly different between groups. Islet cell viability was excellent overall (89%) and did not differ between treatment protocol. Islet function was best in groups treated with 300 mOsm of glucose (stimulation index [SI] = 3.3), suggesting that the lower concentration of glucose may be preferred for use in canine islet isolation. SOS provides a widely available means for researchers to isolate canine islets for use in islet transplantation or in studies of canine islet physiology. }, number={3}, journal={CELL TRANSPLANTATION}, author={Thompson, Elizabeth M. and Sollinger, Jennifer L. and Opara, Emmanuel C. and Adin, Christopher A.}, year={2018}, month={Mar}, pages={542–550} }