Chitosan (CS) hydrogels are widely used in wound hemostatic agents due to their superior biocompatibility, biodegradability, and hemostatic effect. However, most of them fail to achieve great hemostatic effect because of poor adhesion to bleeding tissues. Also, the conventional implantation surgery of hemostatic hydrogels to internal bleeding wounds may cause secondary trauma to the human body. In this work, catechol-hydroxybutyl chitosan (HBCS-C) has been designed and prepared by grafting hydroxybutyl groups and catechol groups to the CS backbones. The multifunctional HBCS-C hydrogels are fabricated with the properties of thermosensitivity, injectability, tissue-adhesion, biodegradation, biocompatibility, and wound hemostasis. They exhibit excellent liquid-gel transition at different temperatures, through the changes of hydrophilic−hydrophobic interaction and hydrogen bonds generating from hydroxybutyl groups. By the multiple interactions between catechol groups/amino groups and tissues, the biocompatible hydrogels can strongly adhere on the surface of tissue. To further study, the bleeding rat-liver models are made to evaluate the hemostatic effects. After injecting the hydrogel precursor solution into the rat body, the hydrogels are not only formed in situ within 30 s but are also firmly adhered to the bleeding tissues which shows effective hemostasis. The injectability and tissue-adhesion improvement in this study gives a new insight into hemostatic agents, and the multifunctional hydrogels have a great potential in the biomedical application.

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recognize and bind to tumor-associated antigens such as CD19 and epidermal growth factor receptor (EGFR) before releasing cytotoxic granules and effector cytokines to destroy cancer cells. [3] CAR-T therapy has shown remarkable success against CD19 expressing B cell hematological malignancies and, thus far, five products (Kymriah from Novartis; Yescarta and Tecartus from Kite Pharma/Gilead Sciences; and Breyanzi and Abecma from Bristol-Myers Squibb) have been approved by the US Food and Drug Administration (FDA) for clinical use. [4,5] Currently, there are at least 500 clinical trials registered on ClinicalTrials.gov database using engineered immune cells to treat various cancers including that of the brain, lungs, and skin.Despite the clinical success of CAR-T cells against B cell leukemia, CAR-T therapy still face tremendous challenges in manufacturing, safety, and affordability before it can become a viable clinical option. [6] One of the biggest technical difficulties is to transfect sensitive, primary T cells whereby biomolecules like oligonucleotides and proteins have to be delivered intracellularly and into the nuclei of cells. FDA-approved gold standard viruses and bulk electroporation suffer from low transfection efficiency while also perturbing the critical biological attributes of cells such as proliferation, metabolism, and gene expression. [7] This increases the time and costs for cell expansion, and without an efficient and cost-friendly transfection technology, the price (between USD 0.4-0.5 million per patient) for FDA-approved CAR treatments (Kymriah and Yescarta) will remain unaffordable and untimely. [8] The limitations in conventional transfection techniques have motivated the development of micro-and nanoplatforms such as microfluidics, nanoparticles, and high-aspect-ratio nanostructures to improve immune cell viability and throughput during transfection.Herein, we first provide an overview of CAR-T cell manufacturing, with emphasis on the science of transfection and limitations of traditional technology using viruses and bulk electroporation. There will also be discussion of other cell-based cancer immunotherapy using other types of promising immune cell types. Next, we describe emerging transfection platforms and companies that have been established to overcome gaps in CAR-T transfection. We then provide a list of assays constituting the polyfunctionalities of immune cells that we believe will help the field better assess the robustness and suitability of their transfection methods. Finally, we end off with existing challenges in CAR-T transfection and how overcoming these challenges can significantly enhance the clinical impact of CAR-T therapy.Chimeric antigen receptor T cell (CAR-T) therapy holds great promise for preventing and treating deadly diseases such as cancer. However, it remains challenging to transfect and engineer primary immune cells for clinical cell manufacturing. Conventional tools using viral vectors and bulk electroporation suffer from low efficiency while posing risks ...

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