@article{mantooth_hancock_thompson_varghese_meritet_vrabel_hu_zaharoff_2024, title={Characterization of an Injectable Chitosan Hydrogel for the Tunable, Localized Delivery of Immunotherapeutics}, volume={10}, ISSN={["2373-9878"]}, url={https://doi.org/10.1021/acsbiomaterials.3c01580}, DOI={10.1021/acsbiomaterials.3c01580}, abstractNote={Localized delivery of immunotherapeutics within a tumor has the potential to reduce systemic toxicities and improve treatment outcomes in cancer patients. Unfortunately, local retention of therapeutics following intratumoral injection is problematic and is insufficiently considered. Dense tumor architectures and high interstitial pressures rapidly exclude injections of saline and other low-viscosity solutions. Hydrogel-based delivery systems, on the other hand, can resist shear forces that cause tumor leakage and thus stand to improve the local retention of coformulated therapeutics. The goal of the present work was to construct a novel, injectable hydrogel that could be tuned for localized immunotherapy delivery. A chitosan-based hydrogel, called XCSgel, was developed and subsequently characterized. Nuclear magnetic resonance studies were performed to describe the chemical properties of the new entity, while cryo-scanning electron microscopy allowed for visualization of the hydrogel's cross-linked network. Rheology experiments demonstrated that XCSgel was shear-thinning and self-healing. Biocompatibility studies, both in vitro and in vivo, showed that XCSgel was nontoxic and induced transient mild-to-moderate inflammation. Release studies revealed that coformulated immunotherapeutics were released over days to weeks in a charge-dependent manner. Overall, XCSgel displayed several clinically important features, including injectability, biocompatibility, and imageability. Furthermore, the properties of XCSgel could also be controlled to tune the release of coformulated immunotherapeutics.}, number={2}, journal={ACS BIOMATERIALS SCIENCE & ENGINEERING}, author={Mantooth, Siena M. and Hancock, Asher M. and Thompson, Peter M. and Varghese, P. J. George and Meritet, Danielle M. and Vrabel, Maura R. and Hu, Jingjie and Zaharoff, David A.}, year={2024}, month={Jan}, pages={905–920} } @article{varghese_zhao_chen_hu_2024, title={Chitosan-nanoclay embolic material for catheter-directed arterial embolization}, volume={1}, ISSN={["1552-4965"]}, url={https://doi.org/10.1002/jbm.a.37670}, DOI={10.1002/jbm.a.37670}, abstractNote={Abstract}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A}, author={Varghese, P. J. George and Zhao, Keren and Chen, Peng and Hu, Jingjie}, year={2024}, month={Jan} } @article{zhao_varghese_chen_hu_2024, title={Developing a transcatheter injectable nanoclay- alginate gel for minimally invasive procedures}, volume={152}, ISSN={["1878-0180"]}, url={https://doi.org/10.1016/j.jmbbm.2024.106448}, DOI={10.1016/j.jmbbm.2024.106448}, abstractNote={Shear-thinning materials have held considerable promise as embolic agents due to their capability of transition between solid and liquid state. In this study, a laponite nanoclay (NC)/alginate gel embolic agent was developed, characterized, and studied for transcatheter based minimally invasive procedures. Both NC and alginate are biocompatible and FDA-approved. Due to electrostatic interactions, the NC/alginate gels exhibit shear-thinning properties that are desirable for transcatheter delivery. The unique shear-thinning nature of the NC/alginate gel allows it to function as a fluid-like substance during transcatheter delivery and as a solid-like embolic agent once deployed. To ensure optimal performance and safety in clinical applications, the rheological characteristics were thoroughly investigated to optimize the mechanical properties of the NC/alginate gel, including storage modulus, yield stress/strain, and thixotropy. To improve physicians' experience and enhance the predictability of gel delivery, a combination of experimental and theoretical approaches was used to assess the injection force required for successful delivery of the gel through clinically employed catheters. Overall, NC/alginate gel exhibited excellent stability and tunable injectability by optimizing the composition of each component. These findings highlight the gel's potential as a robust embolic agent for a wide range of minimally invasive procedures.}, journal={JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS}, author={Zhao, Keren and Varghese, P. J. George and Chen, Peng and Hu, Jingjie}, year={2024}, month={Apr} }