Our Projects
Designing a Scalable Bioreactor System for Innovative Extracellular Vesicle-Based Vaccines
This project aims to establish an innovative extracellular vesicle (EV)-based vaccination platform, representing a next-generation approach to addressing the inherent challenges of current vaccine technologies. Traditional vaccines often face limitations such as instability, the need for cold-chain storage, and variable immunogenicity, which can impede their global applicability, particularly in resource-limited settings. By leveraging the unique properties of EVs—natural nanoscale carriers of proteins and RNA—the project seeks to harness their biocompatibility, stability, and ability to effectively present antigens to the immune system.
The proposed platform employs genetically engineered EVs as antigen-presenting carriers, integrating advanced scaffold proteins to display targeted immunogens with remarkable precision and efficiency. This approach allows for the creation of a modular system that can be adapted for diverse immunogens, offering a versatile solution for a wide array of infectious diseases. The scaffold proteins ensure that immunogens are presented in their optimal conformation, maximizing immune activation and reducing the risks associated with incomplete antigen exposure.
Comprehensive characterization will involve cutting-edge analytical techniques to confirm the integrity, stability, and surface display of the targeted immunogens on the EVs. Preclinical evaluations will include rigorous testing of safety, immunogenicity, and efficacy, laying the groundwork for the platform’s clinical potential. This thorough approach ensures that the EV-based vaccines not only meet current standards but also set a new benchmark for vaccine development.
By addressing key challenges such as antigen stability, immunogenicity, and scalable production, this EV-based platform represents a transformative step forward in vaccine technology. It promises to be a robust and adaptable solution capable of overcoming the barriers faced by existing vaccine strategies, ultimately advancing global health and preparing for future infectious disease threats.
Dentin–pulp complex regeneration
A series of studies investigate the potential of various natural compounds as alternatives to traditional intracanal medicaments for regenerative endodontics. Glycyrrhizin (GA), derived from licorice roots, was found to enhance the viability and proliferation of dental pulp stem cells (DPSCs) while overcoming some of the cytotoxic and effectiveness limitations of conventional treatments like calcium hydroxide (Ca(OH)₂) and triple antibiotic paste (TAP). Similarly, rosmarinic acid (RA) from Rosmarinus officinalis (rosemary) demonstrated better DPSC viability and proliferation without the cytotoxic effects seen with Ca(OH)₂ and TAP. Oleanolic acid (OA) also showed promise, supporting cell proliferation with superior biocompatibility compared to conventional medicaments. Lastly, asiaticoside (AC), a compound from Centella asiatica, at concentrations of 12.5–50 µM, promoted significant DPSC proliferation and showed no cytotoxicity, with the 12.5 µM concentration yielding the highest proliferation rate. TAP and Ca(OH)₂, however, reduced DPSC viability at higher concentrations. The anti-inflammatory, antioxidant, and osteogenic properties of these compounds suggest their potential as safer, more effective alternatives for regenerative endodontic treatments, particularly in cases involving immature necrotic teeth. Despite these promising findings, further in vivo studies and clinical trials are essential to confirm their efficacy and application in clinical practice.
Pre-engineered Exosomes derived from Human
Immortalized Mesenchymal Stromal Cell loaded on 3D-Nanoscaffolds in spinal cord injury animal model.
This project focuses on developing a novel therapeutic approach for spinal cord injury (SCI) using pre-engineered extracellular vesicles (EVs) derived from human immortalized mesenchymal stromal cells (ciMSCs). The EVs are genetically modified to express fluorescent and bioluminescent markers such as eGFP, tdTomato, and NanoLuc for enhanced tracking and biodistribution studies. These engineered EVs are then loaded onto three types of advanced 3D nanoscaffolds: 3D-printed hydrogels, nanofiber-hydrogel hybrids, and thermo-responsive injectable hydrogels. These scaffolds are designed to mimic the extracellular matrix (ECM), providing stability and controlled release of EVs at the injury site while promoting neuroregeneration.
The project employs a well-characterized SCI model in Sprague Dawley rats, where EVs are administered either intravenously or locally using the scaffolds. Comprehensive methodologies, including flow cytometry, immunohistochemistry, electrophysiological analysis, and cytokine profiling, will assess the therapeutic impact. Specific markers for immune modulation (e.g., T cells, microglia phenotypes), neuroprotection (e.g., anti-βIII-tubulin, GAP43), and axonal regeneration (e.g., NF200, MBP) will be evaluated. Functional recovery is monitored via diaphragmatic electromyography (EMG) to quantify physiological improvement.
By combining cutting-edge nanotechnology, molecular biology, and regenerative medicine, this study aims to modulate the secondary injury cascade in SCI, facilitating neuroprotection, immune regulation, and functional recovery. The project holds significant potential to advance SCI treatment and establish cell-free, targeted therapies using engineered EVs and innovative scaffold technologies.
CAR-EVs The next-generation of cell-free therapy for Glioblastoma
By integrating CAR technology with extracellular vesicles, CAR-engineered EVs (CAR-EVs) offer an innovative, cell-free platform that combines the targeting precision of CARs with the natural cytotoxic potential of EVs. Beyond carrying CARs for cancer cell detection, EVs also serve as a versatile protein engineering platform that can be enhanced with additional therapeutic agents. For example, CAR-EVs can be loaded with cytotoxic microRNAs (miRNAs) to amplify their cancer-killing effect, or with immune checkpoint inhibitors like CTLA-4 and anti-PD-L1 to help expose cancer cells and disrupt their immune evasion tactics. This additional engineering transforms CAR-EVs into a multifunctional therapy, capable not only of detecting and killing cancer cells but also of modulating the tumor immune microenvironment to enhance immune cell recognition of cancer cells. Unlike CAR-T cells, CAR-EVs can navigate around the tumor’s immunosuppressive environment and do not trigger systemic toxicity, making them an better alternative for the cell- based targeted cancer therapy.
We hypothesize that engineering extracellular vesicles (EVs) derived from cytotoxic T lymphocytes (CTLs) with chimeric antigen receptors (CARs) targeting glioblastoma-specific antigens, such as IL13Rα2, will enhance their ability to detect and kill cancer cells while enabling the native immune system to recognize and attack tumors. By incorporating miR-34a, a lethal microRNA, these CAR-EVs will exhibit amplified cytotoxicity and induce apoptosis in cancer cells. Additionally, the inclusion of immune checkpoint inhibitors, such as anti-PD-L1 and CTLA-4, will disrupt tumor immune evasion, exposing cancer cells to immune detection. Importantly, we hypothesize that this cell-free CAR-EV platform will eliminate the need for chemo-lymphodepletion, overcoming the burdens of immune cell competition and the suppressive tumor microenvironment, while offering a safer and more efficient alternative to CAR-T therapy in glioblastoma treatment.
Dental-Derived Stem Cell Biobank
The Dental-Derived Stem Cell Biobank Project is a pioneering initiative focused on establishing a comprehensive repository of high-quality dental stem cells from sources such as exfoliated deciduous teeth, dental pulp, and periodontal tissues. This biobank aims to support regenerative medicine and cell therapy by providing a reliable source of stem cells for applications like bone regeneration, craniofacial repair, and neurodegenerative disease treatment, while enabling personalized medicine through autologous stem cell banking. It also serves as a centralized resource for researchers, facilitating studies on stem cell differentiation, gene expression, immunomodulation, and tissue engineering, as well as advancing exosome-based therapies and biomaterial interactions. By employing advanced cryopreservation techniques, rigorous quality control, and global accessibility, the biobank ensures long-term viability and functionality of preserved cells, promoting collaborative research and clinical trials. With a vision to become a global hub for dental stem cell resources, this initiative bridges the gap between research and clinical applications, driving innovation in regenerative medicine and improving healthcare outcomes.