@article{yao_li_zhu_li_tasoudis_liu_mei_popowski_caranasos_wang_et al._2024, title={An infusible biologically active adhesive for chemotherapy-related heart failure in elderly rats}, volume={40}, ISSN={["2452-199X"]}, url={http://dx.doi.org/10.1016/j.bioactmat.2024.06.020}, DOI={10.1016/j.bioactmat.2024.06.020}, abstractNote={Chemotherapy-induced cardiotoxicity with subsequent heart failure (HF) is a major cause of morbidity and mortality in cancer survivors worldwide. Chemotherapy-induced HF is exceptionally challenging as it generally manifests in patients who are typically not eligible for left ventricular device implantation or heart transplantation. To explore alternative treatment strategies for cancer survivors suffering from chemotherapy-induced HF, we developed a minimally invasive infusible cardiac stromal cell secretomes adhesive (MISA) that could be delivered locally through an endoscope-guided intrapericardial injection. To mimic the typical clinical presentation of chemotherapy-induced HF in elder patients, we established an aged rat model in which restrictive cardiomyopathy with sequential HF was induced}, journal={BIOACTIVE MATERIALS}, author={Yao, Jialu and Li, Junlang and Zhu, Dashuai and Li, Yuan and Tasoudis, Panagiotis and Liu, Shuo and Mei, Xuan and Popowski, Kristen and Caranasos, Thomas G. and Wang, Haipeng and et al.}, year={2024}, month={Oct}, pages={571–581} } @article{li_sun_zhu_mei_lyu_huang_li_liu_wang_hu_et al._2024, title={Inhalable Stem Cell Exosomes Promote Heart Repair After Myocardial Infarction}, volume={150}, ISSN={["1524-4539"]}, url={https://doi.org/10.1161/CIRCULATIONAHA.123.065005}, DOI={10.1161/CIRCULATIONAHA.123.065005}, abstractNote={BACKGROUND: Exosome therapy shows potential for cardiac repair after injury. However, intrinsic challenges such as short half-life and lack of clear targets hinder the clinical feasibility. Here, we report a noninvasive and repeatable method for exosome delivery through inhalation after myocardial infarction (MI), which we called stem cell–derived exosome nebulization therapy (SCENT). METHODS: Stem cell–derived exosomes were characterized for size distribution and surface markers. C57BL/6 mice with MI model received exosome inhalation treatment through a nebulizer for 7 consecutive days. Echocardiographies were performed to monitor cardiac function after SCENT, and histological analysis helped with the investigation of myocardial repair. Single-cell RNA sequencing of the whole heart was performed to explore the mechanism of action by SCENT. Last, the feasibility, efficacy, and general safety of SCENT were demonstrated in a swine model of MI, facilitated by 3-dimensional cardiac magnetic resonance imaging. RESULTS: Recruitment of exosomes to the ischemic heart after SCENT was detected by ex vivo IVIS imaging and fluorescence microscopy. In a mouse model of MI, SCENT ameliorated cardiac repair by improving left ventricular function, reducing fibrotic tissue, and promoting cardiomyocyte proliferation. Mechanistic studies using single-cell RNA sequencing of mouse heart after SCENT revealed a downregulation of Cd36 in endothelial cells (ECs). In an EC- Cd36 fl/− conditional knockout mouse model, the inhibition of CD36, a fatty acid transporter in ECs, led to a compensatory increase in glucose utilization in the heart and higher ATP generation, which enhanced cardiac contractility. In pigs, cardiac magnetic resonance imaging showed an enhanced ejection fraction (Δ=11.66±5.12%) and fractional shortening (Δ=5.72±2.29%) at day 28 after MI by SCENT treatment compared with controls, along with reduced infarct size and thickened ventricular wall. CONCLUSIONS: In both rodent and swine models, our data proved the feasibility, efficacy, and general safety of SCENT treatment against acute MI injury, laying the groundwork for clinical investigation. Moreover, the EC- Cd36 fl/− mouse model provides the first in vivo evidence showing that conditional EC-CD36 knockout can ameliorate cardiac injury. Our study introduces a noninvasive treatment option for heart disease and identifies new potential therapeutic targets.}, number={9}, journal={CIRCULATION}, author={Li, Junlang and Sun, Shenghuan and Zhu, Dashuai and Mei, Xuan and Lyu, Yongbo and Huang, Ke and Li, Yuan and Liu, Shuo and Wang, Zhenzhen and Hu, Shiqi and et al.}, year={2024}, month={Aug}, pages={710–723} } @article{kwon_wu_li_yuan_lopez_huang_bai_2024, title={On-demand drug delivery bioelectronics through a water-processable low dimensional highly conductive MXene layer}, volume={6}, ISSN={["1473-0189"]}, url={http://dx.doi.org/10.1039/d4lc00234b}, DOI={10.1039/d4lc00234b}, abstractNote={On-demand drug delivery holds great promise to optimize pharmaceutical efficacy while minimizing the side effects. However, existing on-demand drug delivery systems often require complicated manufacturing processes that preclude their wide implementation of a broad range of drugs. In this work, we demonstrate the introduction of MXene-coated microneedles (MNs) into bioelectronics for digitally controllable gate-valve drug delivery. MXenes, featuring high electronic conductivity, excellent biocompatibility, and solution processibility, enable low-cost scalability for printable bioelectronics. In an electrolytic state (}, journal={LAB ON A CHIP}, author={Kwon, Hyeok-jin and Wu, Yizhang and Li, Yuan and Yuan, Gongkai and Lopez, Rene and Huang, Ke and Bai, Wubin}, year={2024}, month={Jun} } @article{kasper_cydis_afridi_smadi_li_charlier_barnes_hohn_cline_carver_et al._2023, title={Development of a bioactive tunable hyaluronic-protein bioconjugate hydrogel for tissue regenerative applications}, url={http://dx.doi.org/10.1039/d2tb02766f}, DOI={10.1039/d2tb02766f}, abstractNote={Hyaluronic acid-based hydrogels conjugated with a fibrinogen linker were found to contribute to faster scaffold degradationviaactive enzymatic breakdown, paving the pathway for use in a variety of multi-purpose tissue engineering applications.}, journal={Journal of Materials Chemistry B}, publisher={Royal Society of Chemistry (RSC)}, author={Kasper, Mary and Cydis, Madison and Afridi, Abdullah and Smadi, Bassam M and Li, Yuan and Charlier, Alban and Barnes, Brooke E. and Hohn, Julia and Cline, Michael and Carver, Wayne and et al.}, year={2023}, month={Jul} } @article{hlavac_bousalis_pallack_li_manousiouthakis_ahmad_schmidt_2023, title={Injectable Neural Hydrogel as in vivo Therapeutic Delivery Vehicle}, volume={1}, url={http://dx.doi.org/10.1007/s40883-022-00292-9}, DOI={10.1007/s40883-022-00292-9}, journal={Regenerative Engineering and Translational Medicine}, publisher={Springer Science and Business Media LLC}, author={Hlavac, Nora and Bousalis, Deanna and Pallack, Emily and Li, Yuan and Manousiouthakis, Eleana and Ahmad, Raffae N. and Schmidt, Christine E.}, year={2023}, month={Jan} } @article{kasper_ellenbogen_li_schmidt_2023, title={Temporal characterization of hyaluronidases after peripheral nerve injury}, url={http://dx.doi.org/10.1371/journal.pone.0289956}, DOI={10.1371/journal.pone.0289956}, abstractNote={Hyaluronic acid (HA) is ubiquitously found in biological tissues and mediates wound healing mechanisms after injury by promoting cell migration and proliferation. With the development of tissue-engineered neural therapeutics, including off-the-shelf grafts for peripheral nerve repair, HA is an attractive material for clinical use because of its various biological roles. HA-based biomaterials have been carefully engineered to elicit specificin vivohost responses, however an important design feature that should be considered in these scaffolds is endogenous degradation. Hyaluronidases (HYALs) are the complementary enzymes that are responsible for HA turnover. Although HYAL expression has been widely characterized in various tissues, including the central nervous system, and for different pathologies, there remains a lack of knowledge of HYAL mediated turnover in peripheral nerve tissue. In this work, gene expression of two hyaluronidases, HYAL1 and HYAL2, and HA-binding receptor, CD44, were studied in two injury models: rat sciatic nerve crush and critical gap transection. HYAL2 and CD44 were shown to be upregulated 3 days after crush injury, whereas HYAL1 was upregulated at 3 weeks, which collectively demonstrate temporal patterning of HA breakdown. Additionally, differences were observed between HYAL and HA expression at 3 weeks when compared for both nerve injury models. The activity of HYAL in peripheral nerve tissue was determined to be approximately 0.11 μmol/min, which could be used to further model HA-based biomaterial breakdown for peripheral nerve applications. Overall, this work provides a landscape of HA turnover in peripheral nerve that can be used for future neural applications.}, journal={PLOS ONE}, author={Kasper, Mary and Ellenbogen, Bret and Li, Yuan and Schmidt, Christine E.}, year={2023}, month={Aug} } @article{hlavac_bousalis_ahmad_pallack_vela_li_mobini_patrick_schmidt_2021, title={Effects of Varied Stimulation Parameters on Adipose-Derived Stem Cell Response to Low-Level Electrical Fields}, url={http://dx.doi.org/10.1007/s10439-021-02875-z}, DOI={10.1007/s10439-021-02875-z}, abstractNote={Exogenous electrical fields have been explored in regenerative medicine to increase cellular expression of pro-regenerative growth factors. Adipose-derived stem cells (ASCs) are attractive for regenerative applications, specifically for neural repair. Little is known about the relationship between low-level electrical stimulation (ES) and ASC regenerative potentiation. In this work, patterns of ASC expression and secretion of growth factors (i.e., secretome) were explored across a range of ES parameters. ASCs were stimulated with low-level stimulation (20 mV/mm) at varied pulse frequencies, durations, and with alternating versus direct current. Frequency and duration had the most significant effects on growth factor expression. While a range of stimulation frequencies (1, 20, 1000 Hz) applied intermittently (1 h × 3 days) induced upregulation of general wound healing factors, neural-specific factors were only increased at 1 Hz. Moreover, the most optimal expression of neural growth factors was achieved when ASCs were exposed to 1 Hz pulses continuously for 24 h. In evaluation of secretome, apparent inconsistencies were observed across biological replications. Nonetheless, ASC secretome (from 1 Hz, 24 h ES) caused significant increase in neurite extension compared to non-stimulated control. Overall, ASCs are sensitive to ES parameters at low field strengths, notably pulse frequency and stimulation duration.}, journal={Annals of Biomedical Engineering}, author={Hlavac, Nora and Bousalis, Deanna and Ahmad, Raffae N. and Pallack, Emily and Vela, Angelique and Li, Yuan and Mobini, Sahba and Patrick, Erin and Schmidt, Christine}, year={2021}, month={Dec} }