The rise of 3D bioprinting: from organs to personalized medicine

Introduction

Bioprinting is an innovative subset of 3D printing that involves the layer-by-layer deposition of living cells and biomaterials to create structures that mimic the complexity of natural tissues and organs. This technology utilizes bioinks—composed of cells, growth factors, and biocompatible materials—to fabricate constructs with precise architectural and functional properties. The process is meticulously controlled to ensure the viability and correct placement of cells, facilitating the development of tissue constructs that can integrate seamlessly with the human body [1].

The origins of bioprinting are deeply rooted in the evolution of 3D printing technologies. In 1984, Charles Hull introduced stereolithography, a technique that laid the foundation for 3D printing by enabling the creation of objects through the sequential layering of materials. This method initially found applications in engineering and manufacturing. By the late 1990s, advancements in material science led to the development of biocompatible materials suitable for medical applications, paving the way for the emergence of bioprinting [2]. A significant milestone was achieved in 1999 when Dr. Anthony Atala and his team at the Wake Forest Institute for Regenerative Medicine successfully printed a scaffold for a human bladder, which was then seeded with the patient's own cells to create a functional organ [3]. This breakthrough demonstrated the potential of bioprinting in regenerative medicine. Subsequent developments included the printing of miniature functional kidneys in 2002 and the patenting of inkjet bioprinting techniques by Dr. Thomas Boland in 2003, which utilized modified printers to deposit cells into organized 3D matrices [4]. These foundational achievements have propelled bioprinting from a conceptual framework to a burgeoning field with significant clinical implications.

The importance of bioprinting in addressing organ shortages cannot be overstated. Traditional organ transplantation faces significant challenges, including a limited supply of donor organs and the risk of immune rejection. Bioprinting offers a promising solution by enabling the fabrication of patient-specific organs using their own cells, thereby reducing the likelihood of rejection and eliminating the dependence on donor availability [5]. This approach not only has the potential to save countless lives but also to revolutionize the field of regenerative medicine by providing customized therapeutic options tailored to individual patient needs. As research progresses, bioprinting is poised to become a cornerstone technology in the development of functional tissues and organs, addressing the critical demand for transplants and advancing personalized medicine.

Methodology

A systematic and rigorous approach was employed to conduct this literature review, adhering closely to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to ensure transparency and reproducibility. Below, we provide a comprehensive breakdown of the methodology, including the search strategy, inclusion/exclusion criteria, screening process, and quality assessment.

Search strategy

A comprehensive search was conducted in four major academic databases—PubMed, Google Scholar, Scopus, and Web of Science—to identify relevant articles and studies on bioprinting. The search focused on the following keywords and Boolean combinations to maximize coverage:

• "Bioprinting"
• "3D Bioprinting"
• "Organ Transplantation"
• "Regenerative Medicine"
• "Personalized Medicine"
• "Bioinks"
• "Vascularization in Bioprinting"

Synonyms and related terms were included in the search strategy to ensure a wide-ranging retrieval of literature. The search was restricted to peer-reviewed articles published in English between 2000 and 2025. The search strategy was designed to capture the breadth and depth of the field, including technological, biological, and clinical advancements in bioprinting.

Inclusion and exclusion criteria

The following inclusion and exclusion criteria were applied to select relevant studies for this review:

Inclusion criteria:

1. Publications in peer-reviewed journals.
2. Studies focusing specifically on bioprinting technologies and applications.
3. Articles addressing advancements in 3D organ bioprinting, personalized medicine, and regenerative therapies.
4. Papers reporting experimental, computational, or clinical advancements in bioprinting.

Exclusion criteria:

1. Studies published in languages other than English.
2. Non-peer-reviewed articles, conference proceedings, and abstracts.
3. Articles with insufficient methodological detail or irrelevant focus areas.
4. Duplicate studies identified across multiple databases.

Screening and selection process

The initial search yielded a total of 141 articles. The selection process consisted of three phases:

Phase 1: Removal of duplicates

Using reference management software, all retrieved articles were screened for duplicate entries. After this step, 83 unique articles remained.

Phase 2: Title and abstract screening

The titles and abstracts of the remaining articles were independently reviewed by two researchers. Studies that clearly did not meet the inclusion criteria based on the abstract were excluded. This step resulted in the retention of 62 articles.

Phase 3: Full-text screening

The full texts of the remaining 62 articles were assessed for relevance and quality. Articles were excluded if they lacked robust data, detailed methodology, or alignment with the objectives of this review. After this rigorous assessment, 48 articles were selected for inclusion in the final review.

Data extraction

A standardized data extraction form was developed to capture key information from each study, including:

• Author(s) and publication year
• Study design and methodology
• Key findings and conclusions
• Relevance to bioprinting in organ transplantation and regenerative medicine

Data extraction was performed independently by two reviewers to ensure accuracy and consistency. Any discrepancies were resolved through discussion and consensus.

Quality assessment

The quality of the included studies was assessed using standardized tools appropriate for the study design. Experimental studies were evaluated for methodological rigor, including controls, reproducibility, and statistical analyses. Computational and simulation-based studies were assessed for validation metrics and robustness. Clinical studies were reviewed for ethical compliance, sample size, and relevance to translational applications.

Each study was assigned a quality score based on predefined criteria, and only high-quality studies were emphasized in the review’s synthesis.

Limitations of the methodology

While this systematic approach ensured comprehensive coverage of the field, some limitations are acknowledged. First, restricting the search to English-language publications may have excluded relevant studies in other languages. Second, the reliance on peer-reviewed literature may have overlooked emerging but unpublished findings in the field. Finally, the dynamic nature of bioprinting advancements necessitates ongoing updates to this review as new studies become available.

By employing this systematic methodology, the review provides a robust and transparent synthesis of the current state and future directions of bioprinting, addressing its transformative potential in personalized medicine and regenerative therapies.

PRISMA flow diagram

To enhance transparency, a PRISMA flow diagram (Figure 1) is included to illustrate the stepwise process of study selection. The diagram details the number of records identified, screened, excluded, and included at each stage, along with reasons for exclusions.

Figure 1 illustrates the PRIMSA flow diagram

Technologies and techniques in bioprinting

Bioprinting encompasses a range of sophisticated techniques designed to fabricate complex, functional biological structures. Among the primary methods are extrusion-based bioprinting, inkjet bioprinting, and stereolithography. Extrusion-based bioprinting involves the continuous deposition of bioink through a nozzle, allowing for the creation of intricate, cell-laden constructs with high cell density [6]. This method is particularly advantageous for producing larger tissue structures due to its ability to print with a variety of viscosities and materials. Inkjet bioprinting, on the other hand, utilizes thermal or acoustic forces to eject droplets of bioink onto a substrate, enabling high-resolution patterning of cells and biomaterials. This technique is noted for its speed and precision, making it suitable for applications requiring detailed cellular arrangements. Stereolithography employs light to selectively cure photosensitive bioinks, facilitating the construction of structures with exceptional resolution and complexity [7]. This approach is particularly useful for fabricating scaffolds with precise architectural features.

Central to the success of these bioprinting techniques is the selection of appropriate bioinks, which are formulations composed of living cells and biomaterials that mimic the extracellular matrix environment. Bioinks must possess properties that support cell viability, proliferation, and differentiation, while also providing the mechanical integrity necessary for the printed structure [8]. Common bioink components include natural polymers such as alginate, gelatin, and hyaluronic acid, which offer biocompatibility and promote cellular functions. Synthetic polymers like polyethylene glycol (PEG) are also utilized to enhance mechanical properties and tailor degradation rates [9]. The choice of bioink is critical, as it influences the printability, structural stability, and biological performance of the bioprinted construct.

The integration of scaffolds and cellular matrices in bioprinting is essential for replicating the complex architecture of native tissues. Scaffolds provide a three-dimensional framework that supports cell attachment and guides tissue development. In some bioprinting approaches, synthetic materials are printed to form molds or rigid layers that contain the bioink, preventing it from spreading and maintaining the desired shape of the construct [10]. These scaffolds can be designed to degrade over time, allowing the developing tissue to replace the scaffold material as it matures. The combination of scaffolds with cell-laden bioinks enables the fabrication of tissue constructs that closely mimic the structural and functional properties of natural tissues, advancing the field of regenerative medicine [11].

Recent innovations and breakthroughs

Recent advancements in bioprinting have significantly propelled the field toward the fabrication of functional tissues and organs, addressing critical challenges in regenerative medicine. Innovations in bioprinting techniques have enabled the creation of complex tissue architectures that closely mimic their natural counterparts [12]. For instance, researchers have developed methods to bioprint thick adipose tissues with integrated vascular networks, enhancing the viability and functionality of the constructs. These developments are pivotal in overcoming previous limitations related to tissue thickness and nutrient diffusion [13].

Notable progress has been made in the bioprinting of organ prototypes such as the kidney, liver, and heart. In 2024, a study demonstrated the bioprinting of liver tissues with complex vascular architectures, which exhibited essential liver functions and responsiveness to drug treatments [14]. Similarly, advancements in cardiac tissue engineering have led to the successful bioprinting of heart tissues that demonstrate synchronized contractions and electrophysiological properties akin to native heart tissue [15]. These prototypes represent significant milestones toward the development of fully functional bioprinted organs for transplantation.

A critical aspect of bioprinting functional tissues is the incorporation of vascular networks to ensure adequate nutrient and oxygen supply. Recent studies have focused on the synergistic coupling between 3D bioprinting and vascularization strategies to enhance tissue viability. For example, researchers have explored the use of growth factor gradients and co-culture systems to promote the formation of hierarchical vascular networks within bioprinted tissues [16]. Additionally, computational modeling approaches have been employed to design organ-scale synthetic vasculature, facilitating the biomanufacturing of larger and more complex tissue constructs. These efforts are crucial in addressing the challenges associated with vascularization in bioprinted tissues, thereby bringing the field closer to the realization of transplantable bioprinted organs [17].

Applications in regenerative medicine

Bioprinting has emerged as a transformative approach in regenerative medicine, offering innovative solutions for tissue engineering and wound healing. By precisely depositing cells and biomaterials, bioprinting enables the creation of complex tissue constructs that closely mimic native tissues. This technology facilitates the development of customized grafts tailored to patient-specific needs, thereby enhancing the efficacy of treatments for various injuries and degenerative conditions [18].

In the realm of bone and cartilage regeneration, bioprinting has demonstrated significant potential. By utilizing bioinks composed of cells and supportive biomaterials, researchers have successfully fabricated constructs that promote the regeneration of bone and cartilage tissues [19]. These bioprinted structures provide a conducive environment for cell proliferation and differentiation, leading to the restoration of function in damaged skeletal tissues. This approach holds promise for addressing challenges associated with bone defects and cartilage injuries, offering a pathway to improved patient outcomes [20].

Skin bioprinting represents a significant advancement in the treatment of burn injuries. Traditional skin grafting methods often face limitations such as donor site morbidity and limited availability of healthy tissue. Bioprinting offers a promising alternative by enabling the fabrication of skin constructs that can be customized to the patient's wound geometry [21]. This approach not only accelerates the healing process but also improves the aesthetic and functional outcomes for burn victims. Recent studies have highlighted the potential of bioprinted skin substitutes in promoting wound healing and reducing scar formation, thereby enhancing the quality of life for patients with severe burns [22].

Bioprinting for organ transplantation

Bioprinting holds significant promise for organ transplantation, yet several challenges impede the creation of fully functional, transplantable organs. One primary obstacle is replicating the intricate vascular networks essential for nutrient delivery and waste removal in thick tissues. Achieving the necessary cellular density and spatial organization to mimic native tissue functionality remains complex [23]. Additionally, ensuring the mechanical integrity and long-term viability of bioprinted organs poses substantial difficulties. The selection of suitable bioinks that support cell proliferation and differentiation while maintaining printability and structural stability is critical. Moreover, the integration of bioprinted constructs with the host's biological systems, including immune compatibility and the establishment of functional interfaces with existing tissues, presents further challenges [24].

Despite these hurdles, notable research milestones have been achieved in the field of bioprinting for organ transplantation. For instance, researchers have successfully bioprinted liver tissue constructs that exhibit key liver functions, such as albumin production and cytochrome P450 enzyme activity, indicating potential for drug testing and disease modeling applications [25]. In cardiac tissue engineering, advancements have led to the bioprinting of heart tissues demonstrating synchronized contractions and electrophysiological properties similar to native myocardium. These developments represent significant steps toward the realization of bioprinted organs suitable for transplantation [26].

A compelling advantage of bioprinting is its potential to mitigate organ rejection. By utilizing a patient's own cells to create bioinks, bioprinted organs can be customized to the individual's unique genetic and immunological profile, thereby reducing the risk of immune rejection [27]. This personalized approach not only enhances biocompatibility but also eliminates the need for immunosuppressive therapies, which are associated with adverse side effects and increased susceptibility to infections. Furthermore, bioprinting allows for precise control over the spatial distribution of cells and biomaterials, enabling the fabrication of tissue constructs that closely mimic the native architecture and function of organs [28]. This precision facilitates the development of more effective and durable organ replacements, addressing the limitations of current transplantation methods.

Role in personalized medicine

Bioprinting has emerged as a pivotal technology in personalized medicine, enabling the customization of tissues and organs to meet patient-specific requirements. By utilizing a patient's own cells, bioprinting facilitates the creation of bespoke tissue constructs that align with individual anatomical and physiological characteristics, thereby enhancing the efficacy of therapeutic interventions [29]. This approach not only improves treatment outcomes but also minimizes the risk of immune rejection, as the bioprinted tissues are inherently compatible with the patient's immune system.

In the realm of drug testing and disease modeling, bioprinting offers significant advancements. Traditional drug testing methodologies often rely on animal models, which may not accurately replicate human physiological responses, leading to potential discrepancies in drug efficacy and toxicity profiles [30]. Bioprinted human tissue models provide a more accurate platform for evaluating drug responses, thereby reducing the reliance on animal testing and enhancing the predictive validity of preclinical studies [31]. Moreover, these bioprinted models can be tailored to represent specific disease states, allowing for more precise investigations into disease mechanisms and the development of targeted therapies.

The implementation of patient-specific bioprinting also raises important ethical considerations. Issues such as the sourcing of cells, consent for their use, and the long-term implications of creating bioprinted tissues warrant careful deliberation [32]. Additionally, the potential for bioprinting to exacerbate healthcare disparities, particularly if access to such advanced treatments is limited to certain populations, must be addressed. Regulatory frameworks need to evolve to ensure the ethical application of bioprinting technologies, balancing innovation with patient safety and equitable access [33].

Challenges and limitations

Bioprinting, while promising, faces several technological and biological challenges that hinder its progression toward clinical application. A significant issue is scalability; fabricating human-scale tissues and organs necessitates prolonged printing durations, during which maintaining cell viability becomes challenging [34]. Prolonged exposure to environmental stressors during extended print times can compromise cell health, leading to reduced functionality of the bioprinted tissue [35].

Additionally, the complexity of engineering tissues with intricate structures poses substantial hurdles. Achieving the necessary cellular density and spatial organization to mimic native tissue functionality remains complex. Ensuring the mechanical integrity and long-term viability of bioprinted organs poses substantial difficulties [36]. The selection of suitable bioinks that support cell proliferation and differentiation while maintaining printability and structural stability is critical. Moreover, the integration of bioprinted constructs with the host's biological systems, including immune compatibility and the establishment of functional interfaces with existing tissues, presents further challenges [37].

Regulatory and clinical trial challenges further complicate the advancement of bioprinting technologies. The multifaceted nature of bioprinted products, which combine aspects of 3D printing, cell therapy, and custom implants, presents a unique challenge to existing regulatory frameworks [38]. Current regulations may not adequately address the complexities inherent in bioprinted tissues, necessitating the development of new guidelines to ensure safety and efficacy.

Cost and accessibility also pose significant barriers to the widespread adoption of bioprinting technologies. The high costs associated with bioprinting equipment, materials, and specialized personnel limit accessibility, particularly in resource-constrained settings [39]. This economic barrier could exacerbate existing healthcare disparities, restricting the benefits of bioprinting advancements to well-funded institutions and populations. Addressing these cost and accessibility issues is crucial for the equitable implementation of bioprinting in clinical practice [32].

Ethical, legal, and social implications

The emergence of bioprinting technology, particularly in the fabrication of human tissues and organs, presents a complex array of ethical, legal, and social implications that warrant thorough examination.

Ethically, the creation of human tissues and organs through bioprinting raises questions about the moral boundaries of scientific intervention in natural biological processes. While this technology holds the promise of alleviating organ shortages, it also prompts concerns regarding the commodification of human life and the potential for creating entities that challenge our definitions of personhood [40]. Furthermore, the use of human cells in bioprinting necessitates careful consideration of donor consent and the ethical sourcing of biological materials [41].

Legally, bioprinting intersects with complex intellectual property issues. Determining the patentability of bioprinted materials is challenging, as traditional patent systems often exclude products derived from natural phenomena. This ambiguity complicates the protection of innovations in bioprinting and may hinder the field's advancement [42]. Additionally, the classification of bioprinted organs under existing legal frameworks remains unresolved. For instance, if bioprinted organs are deemed equivalent to natural human organs, they may fall under regulations such as the National Organ Transplant Act, which prohibits the sale of human organs, thereby impacting the commercialization of bioprinted products [32].

Socially, bioprinting has the potential to significantly impact global healthcare equity. The high costs associated with bioprinting technologies could limit access to advanced treatments, particularly in low-resource settings, thereby exacerbating existing health disparities [33]. Moreover, the ability to produce human tissues and organs may lead to societal debates regarding the definition of life and the moral status of bioprinted entities. These discussions necessitate inclusive public engagement to navigate the societal implications of bioprinting responsibly [43].

Future directions

The field of bioprinting is poised for significant advancements, driven by emerging trends such as the integration of artificial intelligence (AI) and robotics. The convergence of AI with bioprinting enables the analysis of complex biological data, facilitating the design of more precise and functional tissue constructs [44]. AI algorithms can optimize printing parameters in real-time, enhancing the fidelity and efficiency of the bioprinting process. Additionally, the incorporation of robotic systems, particularly robotic arm-based 3D bioprinting, offers improved automation and precision, allowing for the fabrication of complex tissue structures with high spatial accuracy [45].

Interdisciplinary collaboration plays a pivotal role in advancing bioprinting technologies. The fusion of expertise from fields such as biology, engineering, materials science, and computer science fosters innovation and addresses multifaceted challenges inherent in bioprinting [46]. This collaborative approach, often referred to as bioconvergence, leverages diverse methodologies to solve complex problems in regenerative medicine and beyond.

Looking ahead, the next decade in bioprinting and regenerative medicine is expected to witness transformative developments. Advancements in AI and robotics are anticipated to further refine bioprinting techniques, enabling the production of more complex and functional tissues and organs [47]. Moreover, the ongoing integration of interdisciplinary approaches is likely to yield innovative solutions to current limitations, such as vascularization and tissue maturation. These developments hold the promise of bringing bioprinting closer to clinical applications, potentially revolutionizing personalized medicine and addressing the global shortage of transplantable organs [48].

Conclusion

In conclusion, bioprinting has emerged as a groundbreaking technology with immense potential to revolutionize medicine, addressing critical challenges in organ transplantation, regenerative therapies, and personalized medicine. This literature review has explored the foundational principles, technological advancements, and applications of bioprinting, while shedding light on the ethical, legal, and societal implications. The integration of cutting-edge technologies, such as artificial intelligence and robotics, alongside interdisciplinary collaboration, is paving the way for transformative breakthroughs in the field. Although challenges such as scalability, vascularization, regulatory hurdles, and equitable access remain significant, ongoing research and innovation continue to push the boundaries of what is possible. By envisioning a future where bioprinted tissues and organs become widely available, this field holds the promise to bridge gaps in global healthcare, offering hope for improved patient outcomes and a new era in regenerative medicine.