3D bioprinting has the potential to provide nonanimal alternatives to preclinical testing and revolutionize current clinical and transplantation practices. Realizing this potential requires a concerted effort to develop and advance European standards and regulatory frameworks, ensuring a clear and safe pathway for the clinical integration of 3D bioprinting.
I welcome the discussion raised by Hernández-Huerta and colleagues. While legal provisions regulating the transfer of biological materials are significant, genomic governance goes beyond mere legal compliance. It encompasses transparency, accountability, benefit-sharing, and long-term stewardship. Recent international recommendations emphasize the need for comprehensive governance frameworks for national genomic initiatives.
Cell therapies are increasingly manufactured in closed, automated culture systems, yet decisions about cell quality, safety, and release still rely largely on sparsely executed, destructive, and offline assays. Over the past 5 years, significant progress has been made in developing biosensors capable of real-time measurement of key biochemical and physicochemical indicators including metabolites, ionic species, and protein-associated stress indicators within cell culture environments. However, most systems remain disconnected from manufacturing workflows and fail to support actionable process control. This opinion article discusses the next phase of innovation and the need to reposition biosensors as process analytical technology, shifting the field from descriptive monitoring toward integrated, decision-driven control of cell therapy manufacturing.
Epigenetic editing enables programmable and potentially reversible regulation of chromatin states without altering DNA sequences. By establishing a framework of programmable chromatin engineering, epigenetic editing provides new opportunities for designing climate-resilient crops and advancing next-generation precision breeding.
Calls for public engagement in biotechnology governance are ubiquitous but imprecise, leaving practitioners without actionable guidance and allowing institutions to claim engagement benefits without delivering them. We introduce a precision public engagement framework spanning seven dimensions, making choices explicit, enabling accountability, and closing the gap between engagement and legitimacy.
Musculoskeletal (MSK) disorders remain a leading cause of disability, yet effective disease-modifying therapies are limited by poor translational relevance of conventional models. Organ-on-chip (OoC) technologies have emerged as promising platforms for disease modeling and therapeutic discovery. This review highlights recent advances in patient-derived and induced pluripotent stem cell-based OoC systems, multicellular tissue engineering, biomechanical and immune integration, real-time sensing, and data-driven analytics that enhance physiological relevance and predictive capability. We further discuss automated high-throughput screening and machine learning approaches for scalable drug testing and personalized therapeutic prediction. Finally, we address challenges including reproducibility, vascularization, and standardization, and outline a future roadmap toward precision medicine through intelligent OoC platforms and patient-specific digital twins.
Cerebral ischemic stroke remains a leading cause of disability, with limited options for restoring cerebral blood flow (CBF) and promoting recovery. This study introduces a leaf-mimetic microvascular network to promote poststroke revascularization. The network uses leaf-venation-inspired microchannel templates to direct cell-hydrogel self-assembly into microvascular networks. In a photothrombotic stroke model, the implanted network integrates with host vessels, enhances neovascularization, improves CBF, reduces infarct volume, improves neuronal survival, and promotes functional recovery. Transcriptomic and histological analyses suggest enrichment of potentially reparative neutrophils and reduced inflammation associated with neutrophil extracellular traps as components of the network-associated immune-vascular response. Blocking neutrophil recruitment attenuates network-mediated neovascularization, whereas local delivery of potentially reparative neutrophils partially restores vascular remodeling. These findings provide a preclinical proof of concept that bioinspired microvascular constructs can promote cerebral revascularization and neuroprotection after stroke, while identifying immune-vascular processes that warrant further mechanistic and translational validation.
Biotechnology companies must carefully consider the choice of the first disease indication for their new drug. There are several key elements that can help guide this critical decision. Drawing on years of experience, this article provides an ‘Indication Checklist’ with recommendations designed to help.
Biobanking has played an important role in advancing cell therapy by enabling long-term preservation of cell function, facilitating product transport, and allowing flexibility in infusion scheduling. However, conventional cryopreservation methods rely on high concentrations of dimethyl sulfoxide (DMSO) and serum, which can lead to toxicity, compromise cell viability, complicate post-thaw handling (such as DMSO removal), require additional quality testing, and ultimately reduce therapeutic efficacy. We present a cryopreservation strategy that uses electroporation to introduce protective sugars intracellularly, termed sugar augmented freezing by electroporation (SAFE). Applied across multiple cell types-including chimeric antigen receptor T cells and stem cells-SAFE improved post-thaw viability and expansion by 1.8-fold and enhanced therapeutic efficacy by two-fold compared with standard cryopreservation. Furthermore, SAFE preserved proliferation-associated proteins and metabolites more effectively. Post-thaw cells maintained, and often exceeded, the functional performance of conventionally preserved cells. This work highlights the importance of optimizing cryogenic parameters to achieve greater post-thaw consistency, scalability, and clinical impact on next-generation cell-based therapies.
Recent FDA-approved gene-editing therapies illustrate not only the transformative potential of biotechnologies using CRISPR (clustered regularly interspaced short palindromic repeats)-derived ribonucleoproteins in treating a broad range of diseases but also the spectrum of possible molecular variations CRISPR therapeutics can adopt. These include exagamglogene autotemcel, an ex vivo therapy for hemoglobinopathies using CRISPR nuclease Cas9, and kayjayguran abengcemeran, an in vivo therapy using a protospacer adjacent motif-altered base-editing Cas9 variant for an ultra-rare metabolic disorder. Together, these therapies underscore how far CRISPR has advanced beyond its original use as a tool in biological/biomedical research. In this opinion article, we argue that as CRISPR biotechnologies advance beyond the relative simplicity of in vitro applications, our understanding must also evolve to address the challenges of optimizing ‘on-target’ and ‘off-target’ mutational activities across the diverse contexts in which they occur.
Achieving robust adhesion in wet and biological environments remains a major challenge in biotechnology and medicine. Coacervates are emerging as versatile adhesive platforms that function effectively under hydrated conditions. Their fluid-like nature enables efficient spreading at interfaces, while subsequent mechanical reinforcement stabilizes adhesion without permanent curing. In this review, we present a unifying framework in which adhesion arises from the interplay of interfacial wetting, multivalent interactions, viscoelastic energy dissipation, and kinetic arrest. We discuss how designing phase behavior and arrest dynamics can transform coacervates into functional bioadhesive interfaces for tissue sealing, drug delivery, and biointerface engineering. Finally, we outline challenges in predictive design, spatiotemporal control over arrest, and clinical translation, highlighting adhesive coacervates as multifunctional materials for complex wet environments.
Encapsulation enables microbial technologies across agriculture, biotechnology, and biomedicine by protecting microorganisms from environmental and process-related stresses while extending their functional performance. Natural materials, including polysaccharides such as alginate and chitosan, and biomineral nanoparticles, are emerging as key enablers of encapsulation performance, while supporting sustainability, scalability, and industrial implementation. In this review, we analyze recent advances in natural polymer- and biomineral-based encapsulation systems, focusing on how material selection, encapsulation architecture, and microbial metabolism shape engineered microenvironments. We further discuss how encapsulation becomes technologically and environmentally relevant only when functional gains justify material and processing costs. Finally, we argue for a conceptual shift in encapsulation strategies: from protective supports toward bioinspired microhabitats and living microcapsules capable of programmable microbial functions.
Unconventional T cells (UTCs), including γδ T cells, mucosal-associated invariant T cells, and natural killer T cells, recognize conserved nonpeptide antigens through semi-invariant T cell receptors in an human leukocyte antigen-independent manner, making them attractive candidates for broadly applicable immunotherapies. However, their clinical translation remains limited by poor spatiotemporal control of activation, functional exhaustion, and insufficient tissue homing in vivo, particularly in solid tumors. Biomaterial-based delivery systems provide a promising strategy to overcome these barriers by enabling localized and sustained delivery of UTC ligands, cytokines, and nucleic acids within diseased tissues. Through precise in situ programming of UTC responses, these platforms may enhance therapeutic efficacy and safety. This review summarizes current biomaterial-based strategies and discusses emerging opportunities for in situ UTC programming in human cancers.
Biotechnology and biopharma rely on detailed genome annotations for cell-line engineering, yet most production hosts are nonmodel organisms with limited resources linking sequence to physiology across space and time. A complete four-dimensional genome annotation for Chinese hamster ovary (CHO) cells that links sequence, networks, spatial constraints, process state, and passaging history does not yet exist; current efforts instead provide partial layers that must be connected into an actionable framework. In this opinion article, we illustrate this framework for CHO cells, the dominant platform for recombinant protein biologics. Building such resources on a genomic foundation could reduce trial and error in biologics manufacturing by making cell line and bioprocess design more predictable, transparent, and reproducible.
Dairy proteins are among the most nutritionally and functionally valuable proteins used in food, clinical nutrition, and infant nutrition, yet their supply remains structurally linked to livestock production and dairy processing streams. Precision fermentation offers, based on proven technology, a route to produce individual milk proteins independently of animal agriculture while preserving their molecular identity and application potential. Recent advances in host engineering, secretion capacity, and bioprocess optimization have moved recombinant milk proteins from proof-of-concept toward industrial relevance. However, not all milk proteins are equally tractable fermentation targets. In this opinion article, we examine β-lactoglobulin, α-lactalbumin, and caseins through the lens of nutritional value, functionality, manufacturing complexity, and commercial readiness. We argue that future success will depend less on sequence expression alone than on scalable biomanufacturing technology and know-how, post-translational fidelity, and application-driven target prioritization.
Regulators are accelerating new approach methodologies in cancer drug development. Their capacity to replace animal studies should depend on the context of use. Organoids, chips, and computational models can answer local, measurable questions, whereas whole-body biodistribution, immune handling, organ clearance, chronic toxicity, and therapeutic index still require integrated physiological evidence.
Chronic exposure to arsenite in food and water is a major global health concern, yet no practical strategies exist to prevent ingested arsenite from entering the body through the gastrointestinal tract. Here, we engineered Escherichia coli Nissle 1917 (EcN) to sense and sequester arsenite in situ, creating a probiotic-based approach to reduce host absorption of arsenite. The system involved an arsenite-responsive genetic toggle switch that activated chelator expression upon exposure; after arsenite was removed, it sustained output under biostatic conditions but shut off during active cell division. We also engineered a nontoxic, high-affinity arsenite-binding protein as the chelator. The resulting strain efficiently removed arsenite in vitro while maintaining robust growth. A mass-transfer model guided in vivo dosing, and mouse studies showed that engineered EcN reduced arsenite entry into the bloodstream and promoted its fecal elimination. These findings support the conclusion that this engineered probiotic approach is promising for addressing toxic pollutants in the diet.
Environmentally friendly biopesticides, such as those based on the bacterium Bacillus thuringiensis (Bt), have an important role to play in Integrated Pest Management systems. An increasingly diverse range of pesticidal proteins is being discovered, led by advances in genome sequencing and the bioinformatic identification of candidate genes. In this work, we utilized an AlphaFold3-based structure-prediction approach to identify candidate genes and, in parallel, developed a Bt chassis strain that can be universally used to express new pesticidal proteins. This chassis strain is based on a cdsR deletion strain with a controllable cell death pathway that decouples toxin production from sporulation, enabling cytoplasmic hyperexpression via strong promoters and encapsulation of recombinant proteins. These characteristics provide superior efficacy, UV stability, and environmental safety compared with conventional Bt formulations. Several of the identified proteins displayed insecticidal activity when expressed in this strain, providing a versatile framework for next-generation biocontrol and sustainable pest-management innovation.
