Alakesh

All Publications

• Evolving Transport Properties of Dynamic Hydrogels Enable Self-Tuning of Short- and Long-Term Cargo Delivery. Journal of biomedical materials research. Part A Sen, S., Dong, C., Jons, C. K., Reineking, W., Alakesh, A., Eckman, N., Song, Y. E., Prossnitz, A. N., Appel, E. A. 2026; 114 (4): e70074

  Abstract

  Modulating Cargo Release Using Time-evolving Hydrogels.

  View details for DOI 10.1002/jbm.a.70074

  View details for PubMedID 41924867

• A biomaterial implant model demonstrates that immature neutrophils drive immunopathology following acute injury BIOMATERIALS Dorai, V., Alakesh, A., Guttapadu, R., Sagar, S., Valakatte, M., Raghavan, J., Mohandas, M., Kalpana, S. R., Chandra, N., Jhunjhunwala, S. 2026; 328: 123907

  Abstract

  Individuals with underlying chronic inflammatory conditions are prone to increased morbidity when posed with an additional inflammatory challenge such as an injury or infection. Numerous components of the immune system including immature neutrophils are thought to contribute to the increased morbidity, but ascribing causation remains challenging due to lack of preclinical models to test the contribution of individual components. Herein, we address this challenge by developing and using a mouse model of biomaterial (chitosan-microspheres) implantation, which results in a specific and pronounced expansion of circulating immature neutrophils that exhibit dysregulated effector functions as determined by single cell RNA sequencing and ex vivo functional assays. Next, in this chitosan-implant model, we pose a second inflammatory challenge involving acute lung injury and demonstrate that the immature neutrophils drive an increase in lung immunopathology. Blocking the migration of these immature neutrophils through the administration of therapeutic antibodies or their function using specific small molecule inhibitors, profoundly lowers the immunopathology caused by the inflammatory challenge. Together, these studies demonstrate the utility of a biomaterial-implant model to establish a causal link between immature neutrophils and increased immunopathology and provides insights into new therapeutic strategies for treating individuals with chronic inflammatory ailments.

  View details for DOI 10.1016/j.biomaterials.2025.123907

  View details for Web of Science ID 001641406300001

  View details for PubMedID 41391244

• Enabling global access to potent subunit vaccines with a simple and scalable injectable hydrogel platform. Biomaterials science Ganesh, P., Prossnitz, A. N., Jons, C. K., Eckman, N., Alakesh, A., Song, Y. E., Sen, S., Appel, E. A. 2025

  Abstract

  Vaccines have been crucial to dramatic improvements in global health in recent decades, yet next-generation vaccine technologies remain out of reach for much of the world. In particular, there are two overarching global needs: (i) develop vaccines eliciting more potent and durable immune responses, especially to reduce incidence of highly communicable diseases, and (ii) enable simple and cost-efficient formulation to maximize global access. Here, we develop an injectable hydrogel depot technology prepared through physical mixing of commercially available, generally recognized as safe (GRAS) polymers that can be formulated with subunit vaccine components to improve immune responses compared to standard vaccine formulations. We demonstrate that these hydrogels are shear-thinning and rapidly self-healing, enabling facile administration via injection, and they exhibit high yield stresses required for robust in vivo depot formation post-injection. These rheological properties prolong release of subunit vaccine cargo over a period of weeks, both in vitro and in vivo, and synchronize release kinetics across physicochemically distinct vaccine components (antigens and adjuvants). When used for formulation of subunit vaccines against wild-type SARS-CoV-2 and H5N1 influenza, these hydrogels enhance potency and durability of immune responses. This vaccine formulation technology can improve protection against current and potential future pandemic pathogens.

  View details for DOI 10.1039/d5bm01131k

  View details for PubMedID 41190921