Abstract: The organ transplant system faces numerous challenges, marked by an increasing shortage of organs. The field of 3D bioprinting offers opportunities and a solution to addressing this problem. But as with most emerging technologies, key ethical concerns are raised, especially when the bioprinted organs are publicly funded and made from embryonic stem cells that were donated, and the end products are commercialized. In this paper, concerns surrounding the autonomy of donors, the commodification of human biological materials, and equitable access and benefit to the public are discussed. This literature-based analysis uses existing biomedical ethical frameworks and case law to dive deep into these ethical concerns. Strong informed consent to donors and strict regulations around commercialized bioprinted organs are necessary to combat the ethical risks they bring up. These insights can help inform policymakers, ethicists, researchers, and biomedical engineers to ensure there's a balance between innovation and justice.

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Introduction  

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About 103,223 people are waiting on the national organ transplant list, and approximately 13 people die each day waiting for an organ transplant [11]. One popular solution to this problem is in the field of 3D bioprinting. 3D bioprinting is often described as the layer-by-layer additive robotic biofabrication of three-dimensional functional organ constructs using biological materials, such as living cells [9]. Since the introduction and growth of 3D bioprinting, several ethical issues have arisen, including concerns about the source of cells, commercialization, and ownership. The living cells most commonly used in 3D bioprinting are stem cells, with embryonic and induced pluripotent stem cells being the most frequently employed types. There have been numerous ongoing conversations regarding the ethics of embryonic stem cell research, as it involves the destruction of human embryos early in their development [6]. These embryonic stem cells most commonly come from embryos left over from in vitro fertilization procedures that are donated for research purposes. The donation of these cells for use in bioprinting projects raises questions about the donor's autonomy and informed consent. Furthermore, sections of the donor's informed consent could involve situations where the cells from the donor will be used in bioprinted organs that will be commercialized. Likewise, ethical questions could be raised in scenarios where the research of the commercialized bioprinted organ was publicly funded. Publicly funded biomedical research has the main goal of generating social value through the creation and application of knowledge that can improve the lives of the current and future population [12]. What are the ethical problems of using embryonic stem cells from donors in publicly funded bioprinting projects when the end products are commercialized? I argue that the commercialization of publicly funded bioprinted organs from donated embryonic stem cells is ethically problematic when it compromises donor autonomy, commodifies human life, and fails to equitably benefit the public. The ethical framework I will be using for my argument is the 4 pillars of biomedical ethics, which put the ethics in healthcare into 4 broad categories, which are autonomy, beneficence, nonmaleficence, and social justice [7].

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Scientific and Legal Background 

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     To fully understand the ethical concerns surrounding the use of human embryonic stem cells, it is necessary first to understand the scientific and legal background of their use and funding. Human embryonic stem cells (hESCs) come from embryos that are 3–5 days old and are called blastocysts at this stage [1]. These stem cells are pluripotent, which means they can become any type of cell in the body. This is important in bioprinting, as these cells are capable of creating diverse tissues and organs from a single cell source. hESCs' unique features and pluripotency make them an ideal candidate for regenerative medicine [19]. 

      On the contrary, several questions have been raised regarding the ethics of using hESCs. The main issue brought up is that using hESCs requires the destruction of human embryos, and there have been debates about whether human embryos have moral status and whether the embryo is being harmed. Because of these concerns, the National Institutes of Health (NIH) created guidelines regarding the funding of hESCs research, stating that funding is only allowed for research using hESCs derived from embryos created using in vitro fertilization (IVF) for reproductive purposes and are no longer needed for those purposes with proper informed consent from the donors [10]. Another common solution to the ethical problems of using hESCs is to use induced pluripotent adult stem cells (iPSCs). iPSCs are adult stem cells that have been altered

and reprogrammed to behave like and have properties of hESCs. While this solves the problem of using hESCs, iPSCs may not be as versatile and durable, may not be able to be manipulated to produce all cell types, and are more likely to contain irregularities from environmental hazards, but there is still much research to be done on iPSCs [1]. 

      To understand where commercialization and public funding intersect, it is important to consider legislation on it, such as the Bayh-Dole Act. The Bayh-Dole Act of 1980 enabled universities, small businesses, and nonprofit research institutions to patent, own, and commercialize inventions created with federal funding. The main intention of this law was to promote research into certain diseases by providing a commercial incentive to researchers and institutions [8]. One main criticism of this law is that it has created a culture where profit is valued more than scientific inquiry and investigation. Critics often argue that this law twisted the motivations of researchers who once only had science on their minds [8]. On the other hand, some say that the law created economic growth, increased jobs, incentivized private sector development, and contributed to the success of many startup companies [14]. That being said, the commercialization of publicly funded research has its positives and its negatives that can be applied to biomedical research. It does raise ethical questions surrounding whether or not commercializing publicly funded biomedical research causes inequity.

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Ethical Issues Raised 

Donor Autonomy and Informed Consent 

 

      In the area of bioprinting, ownership has been one key ethical and legal concern. Ownership refers to the legal right to control something, and in this context, it would be their biological material. Some may ask if the donor of the cells should have the authority over the final bioprinted product, or whether the technologist who printed the product using the cells has ownership of the final product [15]. Furthermore, I will not be arguing the ownership concerns of bioprinting, but rather the autonomy side of it. Autonomy is often defined as the right to self-governance and to make decisions over one's own body. In the 4 pillars of bioethics, the respect for autonomy states that each person has the right to make their own decisions and providers have the moral obligation to respect this right [7]. In the case of commercializing bioprinted organs made from embryonic cells from donors, the donors must fully understand how their cells will be used. If donors only consent for their cells to be used for research purposes, commercializing the result would violate their autonomy. Consent to commercialization involves being informed of the long-term implications of it and the profit motives of the researcher, university, or organization. Autonomy requires the donor's full knowledge and understanding of what they are consenting to. It is difficult to ethically justify when the commercialization of their cells isn't completely understood and made explicit to the donor.

 

Commodification of Human Life 

 

     The commercialization of bioprinted organs, especially those derived from hESCs, raises concerns about how human biological material is perceived and utilized in society. Commodification involves turning something that usually isn't bought and sold into a mere commodity. This definition supports that some things are alienable whereas others are not, and that transforming things that are inalienable into a commodity devalues them [3]. Thus, turning organs derived from human parts into products can lead to the loss of human dignity and devalue human parts into objects for sale. This commodification can bring up concerns regarding moral degradation. One can ask whether people will consume more tobacco knowing they can get a pair of new lungs [16]. This illustrates how treating organs as mere commodities alters the perception of human life and biological materials. The notion that this supports is how the commodification of their human parts devalues these parts. Biporinted organs risk being treated as products for sale that can be exchanged and replaced when their function ceases instead of as organs integral to human life. In cases of commercializing bioprinted organs from hESCs, it brings up the ethical question of whether we are selling human life itself. Using the 4 pillars of bioethics, autonomy implies that others should be treated with moral worth and not as a means to an end or as a source of material for profit. Therefore, when the commercialization of these products made from donated hESCs commodifies human life, it becomes ethically troublesome.

 

Access, Equity, and Benefit to the Public 

 

     In addition to issues about the commodification of human life, the commercialization of publicly funded products also raises questions about a fair return to the public. While commercialization is not inherently unethical, it raises concerns when it undermines equitable access, public interests, and autonomy. When research is publicly funded, it is expected that the research will benefit the majority of the public. There's a preference for public funding over industry sponsorship, for there is a belief that the research would benefit the people [5]. If bioprinted organs are commercialized, they may only benefit the wealthy or insured, which would increase healthcare disparities. When donated biological material and taxpayer money are given to benefit the public, the results are meant to be accessible and distributed fairly to the public. The public is essentially paying twice: once through taxes and again through unaffordable prices. When private companies profit and benefit from donated human material and public funding, it creates a system that prioritizes commercialization over fairness. The introduction of new technologies in healthcare can also lead to increased healthcare costs [4]. The commercialization of research can also skew health policy and research since the market favours products and services that generate economic activity [4]. Social justice in the context of the 4 pillars of bioethics calls for limited resources to be shared fairly [7]. Also, in the 4 pillars, beneficence calls to help the public [7]. Thus, it undermines ethical obligations when the outcomes of publicly funded research and donated human biological material are commercialized without restrictions and remain inaccessible and unaffordable.

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Case Study: CIRM Controversy 

 

     The California Institute for Regenerative Medicine (CIRM) was created in 2005 by the California Stem Cell Research and Cures Act (Proposition 71) to spend 3 billion in state funds for stem cell research over the next 10 years [13]. Proposition 71 allowed federal funding for human embryonic stem cell research during a time when serious ethical questions were being raised about said research. The law was signed in response to then-President George W. Bush's tighter restrictions on federal funding for human embryonic stem cell research [18]. 

     Many critics argued that CIRM had little regard for ensuring that the products of the research it funded would benefit the public as a whole. John Simpson of the Foundation for Taxpayer and Consumer Rights, which is a non-profit taxpayer and consumer advocacy group, stated that, “The thing that we’re most interested in is making sure the public-benefit promises that were made are kept, and that just this doesn’t end up being a way of dumping a lot of money in biotech’s pockets with no direct benefit for the people” [17]. Some of CIRM’s expected gene therapies can cost patients up to 4 million [2]. Critics have also pointed out the conflicts of interest present at CIRM. It has a 35-person governing board, which includes many ties to institutions that receive awards from CIRM [18]. The top 5 universities that receive the most grants from CIRM all have ties to the board. Through all its controversy, in 2020, California’s Proposition 14 appeared on ballots to authorize state bonds of 5.5 billion to fund CIRM. The controversy around CIRM highlights why the commercialization of publicly funded human embryonic stem cell research invites ethical debate. 

 

Counterarguments 

 

     One argument for commercialization is that it can enable public benefit by driving innovation. Commercialization is the main way medical products reach the market and consumers, which can advance public health [4]. It is mainly done by private investment, funding clinical trials, and creating patents. It can also serve as a mechanism for translating university research into products that benefit society, and then distributing those products [4]. One could also argue that commercialization is necessary for scaling treatments and ensuring real-world application. Without commercialization, therapies may stay in academic and university labs and never be applied in the real world. Additionally, market incentives and patents can encourage risky research investments that might otherwise never reach patients. For patients suffering urgent needs, accelerating the development of these advancements is the only ethical consideration. Some may argue that commercialization driving funding and investment justifies accepting a degree of inequity. 

Though these points are strong, they do not fully address the inequity issues that commercialization can create. Though beneficence in the 4 pillars supports innovation because it helps patients, justice requires those benefits to be distributed fairly. A treatment that exists but remains inaccessible fails to fully benefit the public. When commercialization is stripped of safeguards and focuses solely on driving profits,

inequity thrives. Commercialization can incentivize companies to prioritize profitable treatments over public need, which could lead to limited access to treatment for lower-income communities. These necessities require strong ethical safeguards, oversight, and regulation to ensure that resulting technologies remain accessible and affordable. Tensions between equitable access and financial interests arise when scientific discoveries become privately controlled products. Without protections, commercialization risks reinforcing disparities rather than reducing them. 

 

Broader Implications 

 

     Beyond the immediate concerns of equity, commodification, and informed consent, the ethical conversation around the commercialization of publicly funded bioprinted organs made from donated hESCs has broader implications. In regard to policy, publicly funded bioprinted organs should face stronger and stricter commercialization limits to ensure fair public benefits. Some regulations could include price caps on these publicly funded therapies, the creation of independent ethics review boards, public-private partnerships that require affordable access, and mandatory informed consent standards. These laws demonstrate the safeguards required when publicly funded medical advancements are commercialized. If the law does not keep pace with science, profit motives may run over ethical obligations. Concerning global equity, one can ask whether the advances in regenerative medicine in wealthier countries will further the gap between high-income and low-income countries. Existing healthcare disparities could deepen on a global scale, especially if access becomes contingent on market price. If only the wealthy benefit, justice is seriously undermined. Without oversight, bioprinting may change in a way that values profit over principles. 

 

Conclusion 

 

     Although bioprinting as a part of regenerative medicine is a major scientific advancement towards solving the problem of long organ transplant waitlists, it raises key ethical concerns that must be addressed. This advanced technology holds great support and hope for the future of regenerative medicine, but it also runs the risk of violating key bioethical principles. When bioprinted organs that were publicly funded and made from donated hESCs are commercialized, it becomes unethical, as it can commodify human life, violate donor autonomy, and fail to adequately help the public. Reform and policy are required to make 3D bioprinted organs beneficial to all. The 4 pillars of medical ethics provide a great background for these ethical issues. Policymakers and researchers must make clearer guardrails in reference to accessibility, informed consent, and respect for human dignity. Along with the evolution of technology, ethical oversight needs to evolve right beside it. The future of bioprinted organs depends on the ethical considerations they bring up, which determines whether patients around the world will be at risk.