@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{willette_gerras_sledge_koch_2023, title={A Case Report of Uterine Body Constriction Precluding Normal Parturition Leading to Dystocia in a Mare}, volume={10}, ISSN={["2306-7381"]}, DOI={10.3390/vetsci10020139}, abstractNote={A 13-year-old multiparous Quarter Horse mare was presented to the Michigan State University’s, Large Animal Emergency service for dystocia. Clinical evaluation revealed a minimally dilated cervix on vaginal examination, with a palpable deceased fetus. Postmortem evaluation following owner-elected humane euthanasia revealed a circumferential, tan, fibrous band at the base of the uterine body that constricted the uterus and was adhered to the left and right ovaries. A routine histologic section of the incarcerating cord attached to the ovary consisted predominately of dense fibrous connective tissue, large blood vessels, and a central oviduct suggestive of a rent in the broad ligament. To the authors’ knowledge, this is the first case report to describe uterine body constriction that precluded vaginal delivery of a fetus in a late gestation mare.}, number={2}, journal={VETERINARY SCIENCES}, author={Willette, Jaclyn and Gerras, Allison and Sledge, Dodd and Koch, Drew}, year={2023}, month={Feb} } @article{koch_schnabel_reynolds_berry_2023, title={Pneumatic compression therapy using the EQ Press accelerates lymphatic flow in healthy equine forelimbs as determined by lymphoscintigraphy}, volume={84}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.22.12.0214}, abstractNote={Abstract}, number={4}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Koch, Drew W. and Schnabel, Lauren V and Reynolds, Justin and Berry, Clifford R.}, year={2023}, month={Apr} } @article{v. schnabel_koch_2023, title={Use of mesenchymal stem cells for tendon healing in veterinary and human medicine: getting to the "core" of the problem through a one health approach}, volume={261}, ISSN={["1943-569X"]}, DOI={10.2460/javma.23.07.0388}, abstractNote={Abstract}, number={10}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={V. Schnabel, Lauren and Koch, Drew W.}, year={2023}, month={Oct}, pages={1435–1442} } @article{koch_berglund_messenger_gilbertie_ellis_schnabel_2022, title={Interleukin-1 beta in tendon injury enhances reparative gene and protein expression in mesenchymal stem cells}, volume={9}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2022.963759}, abstractNote={Tendon injury in the horse carries a high morbidity and monetary burden. Despite appropriate therapy, reinjury is estimated to occur in 50–65% of cases. Although intralesional mesenchymal stem cell (MSC) therapy has improved tissue architecture and reinjury rates, the mechanisms by which they promote repair are still being investigated. Additionally, reevaluating our application of MSCs in tendon injury is necessary given recent evidence that suggests MSCs exposed to inflammation (deemed MSC licensing) have an enhanced reparative effect. However, applying MSC therapy in this context is limited by the inadequate quantification of the temporal cytokine profile in tendon injury, which hinders our ability to administer MSCs into an environment that could potentiate their effect. Therefore, the objectives of this study were to define the temporal cytokine microenvironment in a surgically induced model of equine tendon injury using ultrafiltration probes and subsequently evaluate changes in MSC gene and protein expression following in vitro inflammatory licensing with cytokines of similar concentration as identified in vivo. In our in vivo surgically induced tendon injury model, IL-1β and IL-6 were the predominant pro-inflammatory cytokines present in tendon ultrafiltrate where a discrete peak in cytokine concentration occurred within 48 h following injury. Thereafter, MSCs were licensed in vitro with IL-1β and IL-6 at a concentration identified from the in vivo study; however, only IL-1β induced upregulation of multiple genes beneficial to tendon healing as identified by RNA-sequencing. Specifically, vascular development, ECM synthesis and remodeling, chemokine and growth factor function alteration, and immunomodulation and tissue reparative genes were significantly upregulated. A significant increase in the protein expression of IL-6, VEGF, and PGE2 was confirmed in IL-1β-licensed MSCs compared to naïve MSCs. This study improves our knowledge of the temporal tendon cytokine microenvironment following injury, which could be beneficial for the development and determining optimal timing of administration of regenerative therapies. Furthermore, these data support the need to further study the benefit of MSCs administered within the inflamed tendon microenvironment or exogenously licensed with IL-1β in vitro prior to treatment as licensed MSCs could enhance their therapeutic benefit in the healing tendon.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Koch, Drew W. W. and Berglund, Alix K. K. and Messenger, Kristen M. M. and Gilbertie, Jessica M. M. and Ellis, Ilene M. M. and Schnabel, Lauren V. V.}, year={2022}, month={Aug} } @article{koch_schnabel_ellis_bates_berglund_2022, title={TGF-beta 2 enhances expression of equine bone marrow-derived mesenchymal stem cell paracrine factors with known associations to tendon healing}, volume={13}, ISSN={["1757-6512"]}, DOI={10.1186/s13287-022-03172-9}, abstractNote={Abstract}, number={1}, journal={STEM CELL RESEARCH & THERAPY}, author={Koch, Drew W. and Schnabel, Lauren V and Ellis, Ilene M. and Bates, Rowan E. and Berglund, Alix K.}, year={2022}, month={Sep} }