1Asst. Prof. Rajesh Bhaiyya Tope College of Pharmacy, Chhatrapati Sambhaji Nagar, Maharashtra India
2Asst. Prof. Rajshree College of Pharmacy, Mehkar, Maharashtra India
3M. Pharm, Department of Pharmaceutical Quality Assurance, H. R. Patel Institute of Pharmaceutical Education and Research Shirpur, Maharashtra India.
4B. Pharmacy, Shri Sant Gajanan Maharaj College of Pharmacy, Buldhana, Maharashtra India
5Rajarshi Shahu College of Pharmacy, Buldhana, Maharashtra India
Pharmacognosy plays a pivotal role in identifying, extracting, and standardizing bioactive phytocompounds that form the basis of numerous modern and traditional medicines. However, challenges such as overharvesting, habitat loss, climate change, and long growth cycles hinder sustainable production of medicinal plants. 3D bioprinting, an advanced additive manufacturing technology, offers a novel approach to plant tissue engineering by enabling precise spatial organization of plant cells within custom bioinks for scalable, controlled phytochemical synthesis. This review explores the intersection of 3D bioprinting and pharmacognosy, highlighting its potential in conservation of endangered medicinal plants, optimization of secondary metabolite production, and development of customized phytomedicine delivery systems. We discuss key bioprinting modalities inkjet, extrusion-based, and laser-assisted and their adaptation for plant cells, along with bioink formulations tailored for viability, differentiation, and metabolite yield. Case studies demonstrate successful production of high-value compounds such as paclitaxel, vincristine, and artemisinin from bioprinted plant constructs. Advantages over conventional plant tissue culture include improved reproducibility, scalability, and reduced environmental dependence. The review also addresses challenges in bioink optimization, large-scale manufacturing, cost, and regulatory frameworks. Future prospects encompass AI-guided construct design, portable on-demand phytochemical production in remote or space environments, and integration with synthetic biology for programmable metabolite pathways. By converging biotechnology, additive manufacturing, and traditional pharmacognosy, 3D bioprinting holds promise as a transformative tool for sustainable drug development and biodiversity preservation.
Pharmacognosy, the scientific discipline concerned with the study of medicinal plants, fungi, and other natural sources, has historically been a cornerstone of drug discovery. It encompasses the identification, extraction, characterization, and quality control of bioactive natural products that form the basis of both traditional and modern therapeutics (1). Over 50% of clinically approved drugs are derived from, or inspired by, natural compounds, highlighting pharmacognosy’s central role in the pharmaceutical pipeline (2). In the modern research era, pharmacognosy integrates advanced techniques such as metabolomics, molecular docking, and biotechnology to optimize the discovery and utilization of bioactive molecules (3). Bioactive phytocompounds secondary metabolites such as alkaloids, flavonoids, terpenoids, saponins, and phenolic acids are crucial in both ethnomedicine and evidence-based pharmacotherapy. They exhibit diverse pharmacological activities including anti-inflammatory, antimicrobial, anticancer, and neuroprotective effects (4). In traditional medicine systems such as Ayurveda, Traditional Chinese Medicine (TCM), and Unani, plant-derived phytochemicals are central to therapeutic practice. In modern medicine, compounds like paclitaxel, artemisinin, and vincristine illustrate how plant-derived molecules can be translated into globally significant drugs (5). The increasing demand for phytochemicals has introduced several critical challenges to the conservation and large-scale production of medicinal plants. Firstly, overharvesting and habitat loss (6) continue to threaten biodiversity and jeopardize the sustainability of natural populations. Secondly, climate change (7) has a significant impact on the biosynthesis of phytochemicals, often leading to variations in both the quality and yield of these compounds. Another major hurdle is the lengthy growth cycles of many medicinal plants (8), which limit their scalability for industrial production. In addition, batch-to-batch variability in the content of active compounds (9) creates difficulties in achieving consistent and standardized drug formulations. Although biotechnological approaches such as plant tissue culture and metabolic engineering (10) have been employed to address these problems, they still fall short in delivering large-scale, cost-effective production systems.3D bioprinting, originally developed for regenerative medicine, has emerged as a promising tool for producing complex biological constructs with high spatial precision. In pharmacognosy, it offers the possibility of creating plant cell-based bio-inks, enabling on demand production of phytochemicals under controlled conditions without relying on seasonal growth cycles (11). Techniques such as extrusion-based printing, inkjet bioprinting, and laser-assisted bioprinting can be adapted to print viable plant tissues capable of sustained metabolite biosynthesis (12). Additionally, 3D printing facilitates the design of customizable dosage forms incorporating plant extracts, thereby improving drug delivery, stability, and patient compliance (13). This review aims to explore the convergence of 3D bioprinting technologies and pharmacognosy as a sustainable, scalable, and innovative approach to the conservation and production of bioactive phytocompounds. We assess current advancements in plant cell-based bio-inks, explore bioprinted phytochemical production systems, and discuss their potential in reducing dependence on wild plant harvesting. Furthermore, the review outlines challenges in bio-ink formulation, scaling, and regulatory approval, and presents future research trajectories towards integrating 3D bioprinting into herbal drug development pipelines.
Figure 1. Schematic representation of green bioprinting for plant cell culture engineering.
The process involves deriving callus suspension cultures from plants, followed by structured immobilization using 3D bioprinting techniques. This approach enables precise control over culture geometry, material composition, and perfusion, thereby optimizing cell activity, metabolite yield, and cell–cell interactions for enhanced phytochemical production.
2. BASICS OF 3D BIOPRINTING
2.1 Working Principle of 3D Bioprinting
3D bioprinting is an additive manufacturing process that enables the precise layer-by-layer deposition of bioinks comprising living cells, biomaterials, and signaling molecules into three-dimensional structures that mimic biological tissues (14). The technique is guided by computer-aided design (CAD) models, which are converted into machine-readable instructions. These instructions direct the printer to deposit the bioink according to pre-defined geometries. For plant-based applications in pharmacognosy, the bioink can contain dedifferentiated plant cells or organ-specific cultures capable of synthesizing target phytochemicals (15). The process involves three key stages:
2.2 Types of 3D Bioprinting Technologies
2.2.1 Inkjet Bioprinting
Inkjet bioprinting uses thermal or piezoelectric actuators to eject droplets of bioink onto a substrate. It is a non-contact, high-speed method suitable for low-viscosity bioinks (17). Its resolution ranges from 20–100 μm, making it effective for printing delicate plant cell patterns. However, droplet formation limits the concentration of cells and biomaterials, and thermal inkjet systems may induce stress on temperature-sensitive plant metabolites (18).
Figure 2. Schematic representation of inkjet-based 3D bioprinting techniques.
Inkjet bioprinting dispenses droplets of bioink containing polymers and cells onto a collection plate through precise control mechanisms. Two common approaches include (A) thermal inkjet printing, which uses localized heating to generate droplets, and (B) piezoelectric inkjet printing, which employs piezo actuators to create pressure pulses for droplet ejection. These methods allow high-resolution patterning suitable for complex biological constructs.
2.2.2 Extrusion-Based Bioprinting
Extrusion-based bioprinting employs pneumatic, piston, or screw-driven systems to extrude continuous filaments of bioink through a nozzle (19). It accommodates a wide range of viscosities (30–6×10? mPa·s) and is ideal for encapsulating high-density plant cells in hydrogels (20). Its advantages include scalability and versatility, but it may exert shear stress on plant cells, potentially affecting viability and metabolite productivity (21).
Figure 3. Schematic illustration of extrusion-based 3D bioprinting methods.
Extrusion-based bioprinting involves the continuous deposition of bioink containing polymers and cells through a nozzle onto a collection plate. Two main extrusion mechanisms are shown: (A) pneumatic-driven extrusion, which uses compressed air to push the bioink, and (B) piston-driven extrusion, which relies on mechanical force from a piston. This technique allows the fabrication of complex 3D structures with controlled geometry and material composition.
2.2.3 Laser-Assisted Bioprinting (LAB)
LAB uses a focused laser pulse to generate high-pressure microbubbles that propel bioink droplets onto the substrate (22). It provides high resolution (<10 μm), contactless printing, and minimal shear stress, preserving cell viability. This technique is particularly promising for rare or sensitive plant cell lines used in high-value phytochemical production (23). However, LAB is costly and technically complex, limiting widespread adoption (24).
Figure 4: Schematic representation of Laser-Assisted 3D Bioprinting (LAB) illustrating the deposition of bioink droplets through laser-induced forward transfer onto a collection plate.
Laser-Assisted Bioprinting (LAB) uses focused laser pulses to transfer bioink droplets from a donor layer to a substrate with high precision. This technique enables the patterning of cells and biomaterials without direct nozzle contact, reducing mechanical stress. LAB is particularly advantageous for fabricating complex tissue structures with controlled spatial arrangement.
2.3 Commonly Used Bioinks and Biomaterials
Bioinks used in plant-based bioprinting are carefully formulated to combine structural polymers with nutrient media, creating an environment that supports both cell viability and the biosynthesis of valuable metabolites. Among the most commonly used materials are polysaccharide-based hydrogels such as alginate, pectin, and carrageenan, which offer structural stability and closely mimic the plant extracellular matrix (25). Cellulose derivatives, including carboxymethylcellulose and hydroxypropyl methylcellulose, are also frequently incorporated to enhance the rheological properties of the bioink and improve print fidelity (26). To further support cellular functions, protein-based additives like gelatin and soy protein isolate are added to promote cell attachment and enhance nutrient retention (27). In addition, plant tissue culture media such as Murashige and Skoog or Gamborg’s B5 provide essential macro- and micronutrients along with plant growth regulators necessary for sustained growth and development (28). Recent innovations in the field have introduced nanomaterial-reinforced bioinks such as those incorporating cellulose nanofibers or carbon nanotubes which significantly improve the mechanical strength of the printed structures and can also boost the production of secondary metabolites.
2.4 Advantages over Conventional Plant Tissue Culture
While traditional plant tissue culture (PTC) methods such as callus and suspension cultures have been widely employed for phytochemical production, they present notable limitations, particularly in terms of scalability, structural control, and the spatial organization of plant cells. In contrast, 3D bioprinting offers a range of advantages that address these shortcomings and significantly enhance the efficiency of phytochemical production (29). One key benefit of 3D bioprinting is its ability to precisely control the spatial placement of plant cells and their surrounding microenvironments, which can lead to improved regulation of metabolite biosynthesis pathways. The technology also supports scalability through automated and reproducible fabrication processes, reducing batch-to-batch variability. Furthermore, 3D bioprinting allows for co-culture strategies, enabling the creation of multicellular constructs that closely mimic the natural architecture of plant tissues. In addition to structural advantages, optimized microenvironments within bioprinted constructs can significantly reduce growth times by accelerating cell proliferation and metabolite accumulation. From a sustainability perspective, 3D bioprinting reduces dependence on arable land and water resources compared to conventional field cultivation, thereby contributing to biodiversity conservation and more environmentally responsible production systems.
3. Intersection Of 3D Bioprinting And Pharmacognosy
3.1 Potential of Bioprinting in Plant Tissue Engineering
3D bioprinting offers transformative potential for plant tissue engineering in pharmacognosy by enabling the fabrication of complex, spatially organized plant tissues capable of producing high-value phytochemicals (30). Unlike conventional propagation techniques, bioprinting allows precise control over cellular arrangement, microenvironment composition, and bioactive metabolite pathways. Dedifferentiated plant cells (e.g., callus cells) can be encapsulated in customized bioinks enriched with plant growth regulators to stimulate organogenesis or secondary metabolite biosynthesis (31). This capacity makes bioprinting an attractive platform for ex situ conservation and industrial-scale metabolite production.
3.2 Comparison with Micropropagation, Callus Culture, and Hairy Root Culture
Micropropagation is widely used for the mass multiplication of plants; however, it typically involves sequential subculturing, making it labour-intensive and limiting its ability to control variability in metabolite yields (32). Callus culture, another common technique for secondary metabolite production, offers potential but is hindered by low differentiation control and significant heterogeneity in biosynthetic activity (33). Hairy root cultures, produced through transformation with Agrobacterium rhizogenes, are capable of generating high levels of certain metabolites. Nevertheless, their efficiency is highly genotype-dependent and presents challenges in achieving uniform scalability (34). In comparison, 3D bioprinting offers distinct advantages that overcome many of these limitations. It allows for precise spatial structuring of different plant cell types, the establishment of reproducible culture conditions, and the integration of multiple cell types within a single construct. Moreover, this technology can incorporate genetically modified plant cells into customized, optimized growth matrices, effectively merging the strengths of genetic engineering with those of tissue engineering to enhance metabolite production and culture efficiency (35).
3.3 Customizing Plant Cell Growth Environments for Secondary Metabolite Production
Bioprinting enables the creation of highly customized microenvironments for plant cells, offering advanced control over various factors that influence metabolite production. One such capability is the regulation of nutrient gradients, allowing for the gradual and spatially controlled release of sugars, nitrogen, and micronutrients. This mimics the function of in vivo plant vasculature, promoting healthier cell growth and more stable metabolite biosynthesis (36). Additionally, bioprinting allows for the localized delivery of phytohormones such as auxins, cytokinins, jasmonates, and salicylic acid. These compounds play a critical role in triggering specific secondary metabolite pathways, enhancing the targeted production of valuable phytochemicals. Another promising approach involves co-culturing plant cells with elicitor-producing microbes, such as endophytic fungi or bacteria, embedded directly within the bioinks. These symbiotic organisms can naturally stimulate metabolite synthesis through biochemical signaling. Furthermore, the integration of photoreactive bioinks enables light-pattern modulation, in which specific wavelengths or intensities of light are applied to influence photosensitive biosynthetic pathways (37). This level of precision allows for the consistent and enhanced production of high-value metabolites like artemisinin, paclitaxel, and resveratrol, effectively overcoming the yield variability commonly associated with traditional cultivation and tissue culture systems.
3.4 Case Examples of Plant-Based Bioinks or Printed Plant Tissues
Several recent studies demonstrate the versatility and potential of plant-based bioprinting for pharmacognosy-driven metabolite production and species preservation. For instance, cell-laden hydrogels derived from Artemisia annua have been successfully bioprinted to produce artemisinin, with yields significantly increased upon elicitation using methyl jasmonate (38). Similarly, bioinks based on Catharanthus roseus callus cultures have been printed into vascularized constructs, resulting in enhanced vinblastine biosynthesis and higher alkaloid content compared to traditional suspension cultures. In another approach, decellularized leaf scaffolds from Spinacia oleracea (spinach) were reseeded with medicinal plant cells, demonstrating the feasibility of using large, naturally vascularized surfaces for scalable phytochemical production. Additionally, hairy root-derived bioinks from Arachis hypogaea have been printed into lattice structures, enabling optimized stilbene production through improved nutrient and oxygen diffusion (39). Collectively, these examples underscore the broad applicability of 3D bioprinting in advancing metabolite production, preserving valuable plant species, and creating innovative platforms for plant-based pharmaceutical research.
4. Conservation of Medicinal Plant Species
4.1 Role of 3D Bioprinting in Preserving Endangered or Rare Medicinal Plants
The depletion of wild populations of medicinal plants due to overharvesting, habitat loss, and climate change has intensified the need for innovative conservation strategies. 3D bioprinting presents a novel ex situ approach to propagate rare and endangered species by cultivating plant cells in controlled environments without extracting them from natural habitats (40). By embedding dedifferentiated plant cells from endangered species into custom bioinks, researchers can create tissue analogues that maintain the biosynthetic potential of the original plant. This enables sustainable sourcing of phytochemicals from critically endangered plants like Taxus brevifolia (paclitaxel) and Podophyllum hexandrum (podophyllotoxin) (41).
4.2 Bioprinting as a Tool for Ex Situ Conservation
Ex situ conservation involves the preservation of biological material outside its natural habitat, traditionally achieved through botanical gardens, seed banks, and tissue culture repositories. 3D bioprinting extends this concept by enabling on-demand regeneration of plant tissues with high morphological fidelity (42). Compared to conventional tissue culture, bioprinting offers precise spatial arrangement of cells, enhancing tissue functionality and allowing for the continuous production of metabolites in bioreactors. This method can be integrated with modular growth chambers, enabling preservation and utilization simultaneously (43).
4.3 Genetic Fidelity and Biodiversity Preservation
Maintaining genetic fidelity is crucial for preserving the biochemical profile and adaptive traits of endangered plants. 3D bioprinting uses cell lines or meristematic tissues with minimal subculturing cycles, reducing somaclonal variation often observed in traditional plant tissue cultures (44). The encapsulation process in bioinks also shields plant cells from contamination and genetic drift, preserving species-specific metabolite pathways. Through standardized digital blueprints of plant tissues, genetic information can be archived and reproduced accurately across laboratories worldwide, contributing to global biodiversity databases (45).
4.4 Potential Integration with Cryopreservation and Plant Cell Banks
The integration of 3D bioprinting with cryopreservation and plant cell banking could revolutionize conservation practices. Cryopreservation allows long-term storage of plant cells, tissues, or bioinks at ultra-low temperatures without loss of viability or metabolic potential (46). This stored material can later be thawed and bioprinted into functional tissues for research or metabolite production. By establishing digital and cryogenic repositories of bioprintable plant bioinks, it is possible to create a global plant cell bank that safeguards phytochemical diversity for future pharmaceutical use (47). Such a network could be invaluable in restoring threatened species and rapidly responding to supply shortages of plant-derived drugs.
5. Production of Bioactive Phytocompounds
5.1 Enhancement of Secondary Metabolite Yield through Bioprinted Plant Tissues
3D bioprinting offers a platform for high-density plant cell immobilization within optimized hydrogel matrices, enabling elevated yields of target phytochemicals (48). By controlling spatial arrangement and nutrient diffusion, it is possible to maximize biosynthetic pathway activity. Studies with Taxus spp. cells in bioprinted constructs demonstrated significantly higher paclitaxel production compared to suspension cultures when elicited with methyl jasmonate. Similarly, printed Catharanthus roseus callus cultures have shown enhanced alkaloid production, including vinblastine and vincristine, due to localized microenvironment optimization (49).
5.2 Engineering Metabolic Pathways in Printed Plant Cells
When combined with 3D bioprinting, metabolic engineering offers a powerful means to precisely control and optimize biosynthetic pathways within plant cells (50). One common strategy involves the overexpression of key enzymes involved in target pathways for example, enhancing the activity of taxadiene synthase to boost paclitaxel production. Another approach focuses on suppressing competing metabolic routes to ensure that cellular precursors are directed toward the synthesis of the desired compound, thereby increasing yield efficiency. Additionally, advances in synthetic biology allow for the integration of engineered genetic circuits into plant cells, enabling inducible metabolite production in response to specific external stimuli such as light or chemical elicitors. The spatial control provided by bioprinting further enhances these capabilities by allowing different cell types to be organized in distinct regions within a construct. This spatial separation facilitates precursor product channeling, effectively mimicking the compartmentalization seen in natural plant tissues and improving metabolic efficiency and specificity (51).
5.3 Controlled Environment for Consistent Quality and Quantity
Unlike traditional cultivation, bioprinted constructs are maintained in bioreactors with tightly regulated conditions including temperature, pH, oxygen, nutrient flow, and light exposure ensuring reproducible phytochemical profiles (52). This approach mitigates batch-to-batch variability common in field-grown plants, where environmental fluctuations can alter metabolite content. The result is standardized quality control, meeting pharmacopeial specifications for herbal medicines (53).
5.4 Examples of High-Value Phytochemicals Produced via Bioprinting
Several high-value phytochemicals have been successfully produced using advanced bioprinting techniques, demonstrating the technology’s potential for pharmaceutical applications. Paclitaxel (Taxol), an anticancer diterpenoid derived from Taxus species, has shown enhanced yields in bioprinted cultures that are elicited with nanoformulated precursors, significantly improving biosynthetic efficiency (54).Similarly, the production of vincristine and vinblastine—two indole alkaloids from Catharanthus roseus has been optimized through the co-culturing of different cell lines within spatially organized printed matrices, which better simulate the interactions found in natural plant tissues (55). Curcumin, a polyphenolic compound from Curcuma longa, benefits from its incorporation into nanoparticle-loaded bioinks, which improve both its stability and the controlled release of the compound for pharmaceutical use (56). Resveratrol, a stilbene produced by Vitis vinifera, has also been effectively synthesized using genetically modified grapevine cells embedded in photoresponsive hydrogels. This setup enables sustained production under controlled light exposure, highlighting the potential of bioprinting to fine-tune metabolite output through environmental modulation (57).
6. Technological and Scientific Challenges
6.1 Limitations in Bioink Formulation for Plant Cells
Plant cell-based bioinks must balance printability, mechanical stability, nutrient diffusion, and cell viability a combination that remains difficult to optimize (58). Unlike animal cells, plant cells have rigid cell walls and distinct osmotic needs, which require bioinks with tailored rheology and ionic composition. Hydrogels such as alginate, pectin, and cellulose derivatives are widely used, but they often limit gas exchange and can impede secondary metabolite secretion. Moreover, elicitors and growth regulators incorporated into bioinks may degrade during printing, reducing their effectiveness (59).
6.2 Viability and Differentiation of Bioprinted Plant Cells
Maintaining long-term viability and functional differentiation of plant cells post-printing is a major hurdle. High shear stress during extrusion can cause plasmolysis or cell death (60). In many cases, only 50–70% of printed plant cells remain viable after 7–14 days. Additionally, achieving organ-specific differentiation (e.g., root vs. leaf tissues) is challenging without precise hormonal and environmental cues. This affects the stability and yield of secondary metabolite production over extended culture periods (61).
6.3 Scale-Up Challenges for Industrial Production
Transitioning from laboratory-scale to industrial-scale bioprinting of plant tissues requires addressing throughput, reproducibility, and cost-effectiveness (62). Large-scale printers must accommodate higher bioink volumes while maintaining resolution and cell viability. Continuous flow bioprinting systems are being explored but require robust sterilization and monitoring to prevent contamination. Furthermore, plant cells often grow more slowly than mammalian cells, making industrial timelines longer and increasing operational costs (63).
6.4 Cost and Technical Expertise Barriers
3D bioprinting setups for plant tissue engineering involve high capital investment in specialized printers, sterile workspaces, and custom bioink formulation equipment (64). Consumables such as purified plant growth regulators, high-grade hydrogels, and controlled-environment bioreactors contribute to recurring expenses. Skilled personnel trained in both plant biotechnology and additive manufacturing are scarce, creating an expertise gap that slows commercial adoption. Without advances in automation and open-source protocols, small research labs and developing countries may face limited access to this technology (65).
7. RECENT ADVANCES AND CASE STUDIES
7.1 Current Research on Plant Cell Bioprinting
Recent years have witnessed a surge in studies exploring green 3D bioprinting, where plant cells are embedded in customized bioinks to produce functional tissues and secondary metabolites (66). Key advances include the development of hydrogel-based formulations such as alginate–pectin blends that support the osmotic and mechanical requirements of plant cells while enabling controlled nutrient release. Additionally, microextrusion-based printing has been optimized for cell wall–rich plant cells, allowing high structural fidelity and minimal viability loss (67).
7.2 Notable Proof-of-Concept Experiments
Proof-of-concept studies have clearly demonstrated the viability of using plant cells in bioprinting for both metabolite production and biopharmaceutical synthesis. One notable example involves the bioprinting of transgenic tobacco BY-2 cells, which were engineered to produce recombinant biodefense proteins. This study showed that printed plant tissues can function as living bioreactors, capable of sustained and targeted protein synthesis (68). In another innovative approach, chaotic bioprinting techniques have been employed to combine plant and microbial cells within patterned hydrogels. This co-culture configuration promotes synergistic interactions that enhance metabolite production, showcasing the benefits of integrating multiple biological systems within a single printed construct. Additionally, decellularized Spinacia oleracea (spinach) leaf scaffolds have been repopulated with medicinal plant cells to recreate in vitro architectures capable of both photosynthesis and metabolite biosynthesis. These experiments emphasize that bioprinting extends far beyond traditional propagation methods, offering a pathway toward functionalized, production-ready plant constructs designed for advanced biotechnological applications (69).
7.3 Emerging Bioinks and Bioreactor Systems for Plant Cell Culture
Recent innovations in bioink composition have significantly advanced the field of plant-based bioprinting. Nanocellulose-reinforced hydrogels have been developed to enhance mechanical stability while also improving gas exchange within printed constructs (70). Additionally, the introduction of photoresponsive polymers enables light-controlled regulation of metabolite production, offering precise temporal control over biosynthetic activity. Bioinks loaded with elicitors have further expanded capabilities by allowing on-demand activation of secondary metabolic pathways, tailoring metabolite synthesis to specific stimuli. At the same time, parallel progress in bioreactor design including perfusion-based systems and rotating wall vessel technologies has improved the cultivation of large-scale plant constructs by facilitating continuous nutrient delivery and efficient waste removal (71). These integrated advancements allow for the seamless coupling of 3D-printed plant tissues with industrial bioprocessing pipelines, paving the way for scalable and sustainable production of valuable phytochemicals.
7.4 Integration with Synthetic Biology
Synthetic biology is increasingly being integrated into plant bioprinting to engineer custom biosynthetic circuits within printed tissues (72). For example, CRISPR/Cas9 technology has been used to optimize metabolic pathways in Catharanthus roseus, enhancing vinblastine production in bioprinted constructs. Additionally, synthetic promoters and light-switchable gene circuits have been embedded in plant cells, allowing precise spatial and temporal control over phytochemical biosynthesis (73). Modular "plug-and-play" genetic toolkits further expand these capabilities by enabling the swapping of biosynthetic modules between different species. This innovation allows a single printed scaffold to produce a variety of metabolites, depending on the genetic program inserted into the cells (74). The fusion of synthetic biology with 3D bioprinting thus promises to create programmable, on-demand phytochemical factories tailored for pharmaceutical applications.
8. Regulatory, Ethical, And Economic Considerations
8.1 Regulatory Framework for Plant-Based 3D Bioprinted Products
The regulatory landscape for plant-derived 3D bioprinted products is still emerging, with most guidelines adapted from conventional biotechnology and tissue culture regulations (75). Plant bioprinting intersects multiple domains pharmaceutical manufacturing, agricultural biotechnology, and biodiversity law necessitating compliance with standards such as the Convention on Biological Diversity (CBD) and Nagoya Protocol for access and benefit-sharing. In the EU, plant-based bioprinted products intended for medicinal use may fall under the Advanced Therapy Medicinal Products (ATMP) framework, though specific plant-focused legislation is lacking. In the US, the FDA currently addresses botanical drug products under 21 CFR Part 312, but plant bioprinting raises unique traceability and biosafety concerns (76).
8.2 Intellectual Property and Patent Issues
Patent protection for 3D bioprinted plant tissues and bioinks is complex due to the overlap of biological material rights, digital design rights, and bioprocess patents (77). The patentability of naturally occurring genes or metabolites is generally excluded in many jurisdictions, but engineered bioink formulations, printing methods, and synthetic biology constructs can be protected. This raises biopiracy concerns, particularly when genetic resources from biodiversity-rich countries are utilized without adequate benefit-sharing. The creation of digital plant tissue blueprints for bioprinting adds further challenges, as these files could be shared globally, complicating enforcement (78).
8.3 Market Potential and Commercial Viability
The market potential for plant-based 3D bioprinting is significant, driven by demand for sustainable production of high-value phytochemicals, personalized herbal therapeutics, and rare medicinal plant preservation (79). Market analyses project that plant-derived bioprinted products could complement or replace certain synthetic production routes, reducing costs for complex natural compounds like paclitaxel or vincristine. However, commercial viability depends on scaling production, reducing bioink and hardware costs, and creating clear regulatory pathways for approval and commercialization. Public private partnerships and open-access bioink libraries may accelerate market entry (80).
8.4 Ethical Concerns in Manipulating Plant Biodiversity
The manipulation of plant cells for bioprinting raises ethical debates about altering natural biodiversity and commodifying genetic resources (81). Critics argue that large-scale production of plant-derived drugs outside their native ecosystems may reduce incentives for in situ conservation. On the other hand, proponents see bioprinting as a tool for preservation without exploitation, minimizing environmental damage. Ethical frameworks must address informed consent from indigenous communities, equitable benefit-sharing, and protection against monopolization of plant genetic resources through patents (82).
9. FUTURE PROSPECTS
9.1 AI-Guided Design of Plant Tissue Constructs
Artificial intelligence (AI) offers transformative potential in optimizing plant tissue bioprinting workflows. Machine learning algorithms can predict optimal bioink compositions, printing parameters, and growth conditions for specific plant cell lines, significantly reducing trial-and-error experimentation (83). Deep learning models can also simulate nutrient diffusion, hormone gradients, and metabolite accumulation within 3D constructs, enabling digital twin models for plant tissue growth. Such AI-guided approaches are expected to shorten development timelines and improve reproducibility in phytochemical production (84).
9.2 Personalized Phytomedicine Production
Bioprinting integrated with AI and metabolomics could enable personalized phytomedicine, where medicinal plant constructs are printed to match an individual’s genetic, metabolic, and therapeutic needs (85). By adjusting plant species selection, biosynthetic pathway activation, and phytochemical ratios, on-demand herbal formulations can be prepared with precise therapeutic profiles. This personalization aligns with the growing demand for precision herbal therapy, where efficacy and safety are optimized for each patient (86).
9.3 On-Demand Printing of Rare Phytochemicals in Remote Areas
The portability of compact 3D bioprinters could make on-site production of rare phytochemicals feasible in remote or resource-limited settings (87). Such systems would eliminate the need for long supply chains, particularly for high-value compounds like paclitaxel or artemisinin, which are often produced far from the point of use. By using freeze-dried plant cell bioinks that can be hydrated and printed locally, healthcare providers in rural clinics could access vital plant-based medicines on demand (88).
9.4 Potential Role in Space Pharmacognosy for Long-Term Missions
Space missions face challenges in pharmaceutical stability and supply due to degradation under cosmic radiation and microgravity (89). 3D bioprinting of medicinal plant tissues aboard spacecraft or space stations could provide continuous, fresh production of phytochemicals for crew health. Research in space plant biology suggests that microgravity may alter secondary metabolism, potentially leading to novel compound profiles. NASA and ESA have explored plant tissue culture modules for deep-space travel, and integrating 3D bioprinting could enable self-sustaining pharmacognosy in extraterrestrial habitats (90).
CONCLUSION
The integration of 3D bioprinting into pharmacognosy represents a ground-breaking approach to addressing long-standing challenges in the sustainable production of bioactive phytocompounds. By enabling the precise fabrication of plant tissues in controlled environments, 3D bioprinting offers a sustainable alternative to conventional cultivation and extraction methods, which are often hindered by environmental fluctuations, long growth periods, and overexploitation of natural resources. This technology not only supports the conservation of endangered medicinal plant species but also facilitates consistent, scalable, and high-yield production of targeted secondary metabolites. The adaptability of bioprinting modalities—coupled with advances in bioink formulation, synthetic biology, and AI-driven design paves the way for customized plant constructs capable of producing complex phytochemicals on demand. Potential applications extend beyond terrestrial use, offering solutions for phytomedicine production in remote areas or even in extra-terrestrial habitats as part of space pharmacognosy. Despite its immense promise, several challenges remain, including optimization of plant-specific bioinks, regulatory standardization, and cost-effectiveness for large-scale implementation. Overcoming these barriers will require interdisciplinary collaboration among pharmacognosists, bioengineers, materials scientists, and policymakers. As technological innovations continue to advance, 3D bioprinting stands poised to become a transformative tool in pharmaceutical research, biodiversity conservation, and global healthcare, bridging the gap between traditional medicinal knowledge and next-generation manufacturing platforms. Ultimately, this convergence of technology and nature holds the potential to ensure a sustainable, efficient, and ethical future for plant-derived drug discovery and production.
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