image: The flowchart details the TIBS-based PDEV production process: (1) sterile seedling cultivation under programmable parameters (temperature, light, immersion cycles); (2) continuous PDEV collection from TIBS culture medium; (3) separation via ultrahigh-speed centrifugation (100,000×g for 120 minutes at 4°C); (4) characterization of high-quality PDEVs using transmission electron microscopy (TEM, for structure), particle size analysis, and zeta potential measurement. TIBS ensures consistent, controllable PDEV production by eliminating environmental interference.
Credit: Food & Medicine Homology, Tsinghua University Press
Plant-derived Extracellular Vesicles (PDEVs)—tiny, lipid bilayer-enclosed vesicles secreted by plant cells—have emerged as a standout in biomedical research, thanks to their rich cargo of proteins, small RNAs, lipids, and plant-specific metabolites. PDEVs from food-medicine homology plants (e.g., ginger, kudzu, purslane) boast unique advantages: ginger PDEVs alleviate colitis and type 2 diabetes-related metabolic disorders, purslane PDEVs improve ulcerative colitis, and kudzu PDEVs enhance bone regeneration in osteoporosis models. With low immunogenicity and high biocompatibility, they are ideal candidates for drug delivery and disease treatment.
Yet, a major bottleneck has held back their progress: inconsistent quality. Traditional PDEV production relies on wild-harvested plants or destructive methods like tissue juicing, which are vulnerable to environmental changes (e.g., light, temperature, microorganisms) and generate artificial vesicles that differ from natural PDEVs in size and function. This leads to “triple heterogeneity”—uneven particle sizes, fluctuating active components, and inconsistent biological functions—undermining the reliability of PDEV-based research and therapies.
Now, a team led by Peng Luo (Guizhou Medical University), Guo-Guang Chen (Zunyi Medical University), and Ji-Shuang Chen (Nanjing Tech University) has developed a game-changing solution: the Temporary Immersion Bioreactor System (TIBS). Their findings, published in Food & Medicine Homology (2025, 2: 9420123), show how TIBS transforms PDEV production through precise, programmable control.
“TIBS fills the gap in controllable PDEV production platforms by combining plant tissue culture with airlift liquid pressure engineering,” explained Peng Luo, a senior author of the study. “We program parameters like 6-hour immersion-aeration cycles, a steady 25±1°C temperature, and a 14h light/10h dark photoperiod. This stable environment ensures PDEVs have consistent metabolite levels—for example, linoleic acid and α-linolenic acid contents are highly uniform across samples—and avoids microbial contamination that degrades vesicles.”
TIBS also excels in efficiency and sustainability. Unlike destructive traditional methods, TIBS enables non-destructive, continuous PDEV collection: plants grow long-term in the system, and PDEVs are harvested by replacing the culture medium regularly, boosting total yield. Its modular design supports large-scale production at low cost—no expensive serum is needed, and energy use is just 60% of traditional solid plant tissue culture.
“Sustainability is key, especially for rare medicinal plants,” noted Guo-Guang Chen. “TIBS recycles plant materials, reducing reliance on wild resources like Dendrobium officinale and Anoectochilus roxburghii. It also produces no harmful waste, aligning with green production. Importantly, TIBS works for multiple food-medicine homology plants—from ginger to Glycyrrhiza uralensis—proving it’s a universal platform.”
To unlock TIBS’ full potential, the team outlines a three-step research paradigm: basic research, technical standardization, and application transformation. Future basic research will explore how TIBS parameters (e.g., medium composition) regulate PDEV secretion—using transcriptomics to analyze genes like the Rab GTPase family—and build “structure-function” models via cryoelectron microscopy. For standardization, the team calls for defining optimal TIBS parameters for different plants, simplifying separation protocols (e.g., adapting 100,000×g ultracentrifugation for TIBS media), and setting mandatory indicators (particle size, zeta potential, marker proteins like flotillin) aligned with international norms such as ISO/TS 21418.
“The end goal is to bring TIBS-produced PDEVs to clinics,” said Ji-Shuang Chen. “We plan to prioritize their use as natural drug carriers for targeted tumor therapy or as immunomodulators—leveraging their polysaccharides to boost anti-tumor immunity. Clinical translation will start with small-scale safety trials, followed by large-sample, multi-center studies to confirm efficacy.”
Policy support will also be critical, the authors stress. A “classified supervision” mechanism—simplifying approvals for PDEVs as food supplements while enforcing strict standards for medicinal use—along with industry-academia-research collaboration and funding for TIBS upgrades, will speed up industrialization.
“TIBS doesn’t just fix quality issues—it builds the scientific and technical foundation for PDEVs to move from labs to clinics,” Peng Luo added. “This breakthrough opens a new chapter for plant-derived vesicles in biomedicine.”
Other contributors include Fu-Xing Shu (Zunyi Medical University & Nanjing Tech University) and Ning-Xian Yang (Guizhou Medical University), who made equal contributions to the work.
The article was published on July 21, 2025, in Food & Medicine Homology.
Conflicts of Interest:
The authors declare no conflicts of interest.
Funding:
This work was supported by National Natural Science Foundation of China (Grant No. 82373981); The Science and Technology Support Program of Guizhou Province (QKH(2025) General 132).
About the Authors
Fu-xing Shu is a Doctor at Zunyi medical university and Nanjing technology university, he focuses on TIBS and plant-drive Extracellular Vesicles research.
Ning-Xian Yang is a professor at Guizhou Medical University and focuses on medicinal plant applications and natural product research.
Dao-pingWang is an associate researcher at State Key Laboratory of Functions and Applications of Medicinal Plants, Natural Products Research Center of Guizhou Province, mainly focuses on focuses on medicinal plant applications and natural product research.
Peng Luo is a professor at Guizhou Medical University and specializes in public health.
For more information about their work, visit the institutional website of Guizhou Medical University.
Guo-Guang Chen is a professor at Nanjing Technology University specializes in the industrialization of medicinal plants and the development of plant-derived bioactive substances.
Ji-Shuang Chen is a professor at Zunyi medical University conducts research in biotechnology and pharmaceutical engineering, with a focus on the standardization and industrialization of plant-derived extracellular vesicles.
Journal
Food & Medicine Homology
Article Title
Harnessing Innovations in Antimicrobial Peptide Design: From AI-Driven Discovery to Precision Targeting Mechanisms
Article Publication Date
11-Jul-2025