The human body, like a precision machine, is no longer a sci-fi fantasy when it comes to "replacing parts." Three thousand years ago, wooden prosthetics from ancient Egypt have evolved into today’s FDA-approved genetically edited pig hearts—replacement-based interventions are becoming a new medical paradigm. Capital and policy are accelerating investment, with China achieving breakthroughs in xenotransplantation and bio-3D printing; however, vascularization, immune rejection, and age assimilation remain three major technical bottlenecks.Article author and source: 36Kr
Around 1000 BCE in ancient Egypt, the priestess Tabaket-en-Mut likely never imagined that the wooden prosthesis she wore after losing her big toe would, 3,000 years later, become a testament to medical history.
Archaeologists speculate that she likely lost this toe due to complications from diabetes. With no modern medicine available at the time, she commissioned a prosthesis made of three wooden toe segments joined together and covered in leather—durable, comfortable, and perfectly fitted to the shape of her残缺 foot. This prosthesis, later known as the "Cairo Toe," is now housed in the National Museum of Egyptian Civilization (NMEC) and is among the oldest functional prosthetics in human history.
Image source: National Museum of Egyptian Civilization (NMEC) official website
It was a humble beginning: replacing a missing item, restoring some degree of functional ability, or simply making the body look presentable.
Today, this "replacement" has moved beyond superficial fixes and reached the core of life. On May 15, 2026, United Therapeutics, a U.S. biotech company, received FDA approval to begin clinical trials for its 10-gene-edited pig heart, the UHeart, marking the start of human trials aimed at commercialization. Once regarded by the public as sensational news stories, "pig heart transplants" and "pig liver transplants"—forms of xenotransplantation—are now aligning with standard medical product evaluation and approval processes, and are poised to become registered, standardized therapies.
From simple cosmetic repairs to precise replacements at the molecular level, looking back at humanity’s medical advancements over the past 3,000 years reveals one consistent goal: replacing broken, malfunctioning, or aged “parts” with functional, youthful, and properly operating ones.
This logic may sound simple, but it underpins the entire history of surgery, transplantation, and modern regenerative medicine: remove the failed components and replace them with biological or synthetic alternatives to get the body running again.
This is the common core of "replacement-based intervention." In May 2025, Nature Aging published the review "Replacement as an Aging Intervention," with Eric Verdin, Director of the Buck Institute for Aging, as the corresponding author, alongside leading aging scientists such as George Church and Vadim Gladyshev. The paper systematically outlines multiple replacement strategies—including cell therapy, tissue engineering, xenotransplantation, and synthetic replacement devices—and for the first time establishes a unified framework for aging intervention centered on "replacement."
In April 2026, *Aging Cell* published a companion commentary article titled "Replacement-Based Ageing Interventions for Systemic Rejuvenation," authored by Professor Vadim N. Gladyshev from Brigham and Women’s Hospital, Harvard Medical School, and Morten Scheibye-Knudsen from the University of Copenhagen, with Chinese author Bohan Zhang (Harvard Medical School) also contributing. The article further proposes a roadmap for integrating replacement therapies with next-generation damage-clearance technologies, clearly defining the conceptual framework of "Replacement-Based Aging Interventions" and systematizing this approach.
This sends a clear signal to both academia and industry: "replacement" is not the exclusive domain of surgeons, but rather a theoretically grounded medical pathway on par with pharmaceuticals and medical devices. Abroad, the FDA has approved human clinical trials involving pig hearts; domestically, the National Medical Insurance Bureau signaled earlier this year that it would establish separate billing codes for bioprinting-assisted procedures (tissues, blood vessels, organs), followed by the Hunan Provincial Medical Insurance Bureau, which promptly defined a government-guided price range of 1,200 to 1,600 yuan. These examples are concrete manifestations of this research framework in practice.
So, where has this human endeavor, which has lasted 3,000 years, reached by 2026?
What is "replacement technology"?
To understand "replacement technology," consider this question: When a machine wears out and its parts break, what do you usually do? Most likely, you don’t repair it—you replace it. So why, with the human body—a highly sophisticated "machine"—do we so often try to fix it instead: taking pills, getting injections, undergoing surgery—rather than simply replacing the faulty parts?
The answer is simple: it couldn’t be done in the past—there were no suitable materials, no anti-rejection drugs, and no methods to grow living tissue. But over the past few decades, these barriers have been gradually overcome.
The aforementioned study in *Aging Cell* defined the "replacement strategy" as one that simultaneously addresses multiple age-related damages rather than targeting only a single biochemical pathway; aims for more systematic and lasting functional restoration rather than transient improvement; and shifts the timing of intervention from "treating after illness" to "replacing before illness occurs."
In other words, "replacement" is no longer a high-stakes gamble like "Cairo's big toe," but rather an active, systematic approach to maintaining health.
Fundamentally, breakthroughs in medical technology have completely expanded the boundaries of replacement, and the 20th century was the true turning point. In 1954, the first kidney transplant enabled failing organs to be replaced by healthy ones; in 1958, the first pacemaker implanted in a human body demonstrated that electronic devices could regulate biological rhythms; in the 1990s, hematopoietic stem cell transplantation became established, extending the survival of some leukemia patients and even offering the possibility of cure...
In the past, people could only perform major repairs on organs; now, replacement capabilities have gradually expanded to include cells (such as stem cell transplants and CAR-T), tissues and organs (such as organs grown from autologous cells and 3D tissue printing), the circulatory system (such as therapeutic plasma exchange - TPE), and even synthetic replacements represented by high-value medical devices and consumables (such as pacemakers) and brain-computer interfaces.
The Immortal Dragons fund in Singapore’s longevity tech sector told 36Kr that among these various levels, "organ and tissue-level replacements have greater relevance to everyday life, clearer commercialization potential, and best demonstrate the maturity of this technology transitioning from the lab to reality."
Founder of Immortal Dragon, Boyang
Currently, a clear and mature hierarchy has emerged in this field.
The first tier consists of already commercialized thin tissue replacements such as skin, cartilage, and cornea. These have simple structures—for example, skin is a “two-dimensional sheet” composed of a few layers of cells, cartilage consists of only one cell type plus extracellular matrix, and the corneal epithelium lacks blood vessels. None of these require solving vascularization, the key challenge in tissue engineering, making them safer and lower-risk, and thus advancing more rapidly toward commercialization.
In the U.S., cell-based skin products such as Apligraf and Epicel have been approved by the FDA and have been clinically used for over 20 years; in the field of cartilage repair, Vericel’s MACI technology (matrix-induced autologous chondrocyte implantation) has also received FDA approval and entered clinical use. The existence of these products demonstrates one thing: even the simplest component replacements have been industrialized.
The second tier primarily refers to hollow organs that have entered human clinical trials but are not yet commercialized, such as the bladder, urethra, and vagina. These are more complex than thin-layer tissues but simpler than solid organs, requiring only a three-layer structure: an inner epithelial layer, a middle smooth muscle layer, and an outer connective tissue layer. Their thin walls allow oxygen and nutrients to diffuse adequately, temporarily bypassing the need for vascularization.
As early as 1999, Anthony Atala’s team (Boston Children’s Hospital, Harvard) harvested urothelial and muscle cells from the bladders of seven children with bladder dysfunction caused by myelomeningocele. These cells were expanded in vitro and seeded onto biodegradable scaffolds to construct new bladders, which were then transplanted back into the patients. The study was published in The Lancet in 2006: follow-up over 2 to 5 years showed that the transplanted bladders remained functional; because autologous cells were used, no immunosuppression was required and no significant rejection occurred, resulting in improved bladder function and quality of life.
The third tier targets solid organs such as the kidneys, liver, and heart. These organs typically require dozens of cell types, intricate vasculature, and complex metabolic functions, making them the "ultimate challenge" in tissue engineering. Currently, the vast majority of truly transplantable engineered solid organs under academic research are still in the experimental stage.
It is clear that the maturity of "replacement technologies" follows a clear pattern: the simpler, thinner, and more hollow the structure, the easier it is to implement; the more complex and reliant on intricate vascular networks, the longer the R&D cycle. This hierarchy represents not only a technological roadmap but also a capital investment timeline—prioritizing mature, commercially viable thin tissues first, then gradually advancing toward hollow and solid organs, where difficulty and returns are directly proportional, providing clear guidance for industry development.
Capital enters the scene, China leads: The industrial wave of "replacement technology"
The industry layout seeks a step-by-step approach, and the development of "replacement technology" must consider both short-term clinical implementation and long-term anti-aging goals. Therefore, current "replacement technology" is not about mass organ replacement as depicted in science fiction, but rather focuses on aligning with clinical necessities and sustaining the company’s foundational viability.
For example, as technology matures, more people will be able to replace artificial joints at the earliest signs of mild joint wear, implant small-diameter grafts at the initial stage of vascular hardening, or optimize bodily function and replenish youthful immune cells by replacing or repairing damaged components as the immune system begins to decline. These interventions fundamentally shift from “reactive repair” to “proactive maintenance.”
When a technology moves from the lab to the clinic, capital is the most sensitive indicator. For decades, replacement technologies were categorized as serious medical interventions—after all, organ and joint replacements are effective but limited in scale and slow-growing. However, with two top-tier journals defining them as a new “aging intervention paradigm,” venture capital’s perspective has fundamentally shifted: replacement is no longer just about “treating disease,” but rather a systemic strategy for health maintenance.
In this wave of innovation, Immortal Dragon was one of the earliest institutions to systematically focus on and bet on the “Replacement Strategy”—the concept of replacing damaged parts of the body with new, fully functional components. Its core principle is that the commercialization of all cutting-edge technologies must first be validated clinically through clear and urgent medical needs, ensuring safety and efficacy to achieve regulatory approval and market launch; once the technology matures and the policy framework is established, applications will gradually expand, ultimately realizing the ultimate value of systemic anti-aging and unlocking a broader market.
Their core assessment is straightforward: human aging is essentially systemic hardware degradation, and repairing it is like patching a leaky ship—it’s hard to keep up with the pace of aging; directly replacing aged components may be a more efficient path to extending lifespan.
Based on this assessment, Immortal Dragon has strategically allocated its $40 million Longevity Fund toward four core areas: replacement-based aging interventions, gene therapy, reversal of neural aging, and accelerating the translation of innovative therapies into practice. To date, Immortal Dragon has invested in over 20 leading global startups and is deeply involved in the entire translation process, from laboratory research to clinical application.
The Immortal Dragon team explains that the optimal intervention strategy varies depending on the stage of the disease. “For example, during early, reversible damage, repair is often more effective because it is low-cost, low-risk, and does not require a donor. In regenerative therapies, promising advances are being made in gene therapy, regenerative medicine, and cell therapy. However, when organ damage progresses to an irreversible stage, the marginal benefits of repair drop sharply, and replacement may become the only viable option. Replacement methods can vary based on donor source, including organs donated voluntarily by humans, animal organs, 3D bioprinted organs, or human organs grown within animals.”
In the short term, Immortal Dragon’s investment projects primarily focus on therapeutic areas with unmet clinical needs, addressing key pain points in traditional medicine to achieve commercial validation. Take its representative investment, Frontier Bio, as an example: it tackles the challenge of small-diameter vascular grafts. The global vascular graft market exceeds $12 billion, but existing synthetic products fail in small-diameter applications (less than 6 mm in diameter) at rates as high as 65%. This is because the absence of an endothelial layer causes blood to directly contact artificial materials, triggering thrombosis. Moreover, conventional tissue-engineered vessels require harvesting cells from the patient and culturing them in a lab for weeks or even months before implantation—many patients cannot wait that long.
Frontier Bio’s breakthrough lies in its "single-surgery graft." At the start of the procedure, a small amount of tissue is harvested from the patient’s subcutaneous abdominal fat, adipose-derived stem cells are isolated, and these cells are immediately seeded onto a biodegradable polymer scaffold made by electrospinning—all completed right on the operating table. Animal studies have shown that, after 14 days, the graft has developed a continuous endothelial layer and has begun integrating with the host’s vasculature.
“This means you can bypass thrombosis and lengthy in vitro culturing by using an autologous, living, ready-to-use vascular substitute. Moreover, since the graft uses the patient’s own cells, there is no risk of rejection and no need for donor matching, thereby addressing many of the immune compatibility issues associated with allogeneic cell products,” said Bu Xiu Zhen Long.
Another portfolio company, U.S. biotech firm Immune Bridge, has hit another critical challenge in allogeneic cell therapy: immune cells from different adult donors vary in quality, while iPSC-derived immune cells have limited functionality and often require additional gene editing to compensate.
Immune Bridge’s solution returns to the most “youthful” source: neonatal umbilical cord blood. They have developed a small molecule, IBR403, that can massively expand hematopoietic stem cells in umbilical cord blood while preserving their stemness and pluripotency. The expanded cells can differentiate into various immune cells, including NK, T, and B cells—effectively creating a “warehouse of young immune cells.”
These cutting-edge projects have attracted industry attention because they represent a trend: "disruptive technology" is evolving from isolated cases into replicable, scalable technology platforms.
During this process, China has stood out particularly, “especially in key areas such as xenotransplantation, bio-3D printing, and cell therapy,” according to BuXiu ZhenLong. This prominence is not driven by just one or two standout products, but by the entire ecosystem accelerating toward maturity—from early-stage research and development to manufacturing processes, and from regulatory reforms to payment systems—a foundational infrastructure capable of supporting long-term innovation is gradually taking shape.
Immortal Dragon Team
Taking xenotransplantation as an example, China has achieved a breakthrough from 0 to 1. On the research front, the team led by Academician Dou Kefeng of the Air Force Medical University completed the world’s first gene-edited pig liver transplant into a human in 2024; the transplanted pig liver functioned successfully for 10 days, secreting bile and synthesizing albumin, with the results published in Nature. On the industrial front, leading company Zhongke Aoge has disclosed that it has built a total of approximately 330 acres of medical pig industrial parks, including a medical pig breeding base capable of producing 2,000 medical experimental pigs annually—a development that has attracted early-stage venture capital and industry funds such as Lightspeed China Partners, YuanSheng Capital, and Betta Pharmaceuticals Industry Fund.
From a global perspective, the industrial wave of replacement technology has only just begun. It may still be too early to say exactly how far it will go or when it will truly benefit ordinary people. But one thing is certain: replacement technology has evolved from an academic concept into a real technological frontier, with capital, policy, and clinical resources converging on it. The progress over the next decade is likely to surpass the total of the past several decades.
Bottlenecks still exist—the three critical challenges for replacing technology
Although the prospects of "replacement technology" are exciting, we cannot ignore a reality: currently, commercially viable replacement products are mostly limited to "simple parts" such as skin and cartilage. To upgrade them to "core parts" like kidneys and hearts, at least three major technical hurdles must be overcome.
The primary challenge lies in vascularization. Any tissue thicker than 200 micrometers without an interconnected capillary network cannot deliver oxygen and nutrients to its interior, leading to rapid cell death. Thin tissues like skin and cartilage can circumvent this issue, but solid organs such as the liver, kidneys, and heart require the construction of intricate vascular networks. Although progress has been made in 3D printing and biomaterial technologies, there remains a significant gap between current capabilities and clinically stable vascularization. Without functional blood vessels, organs cannot survive—this is the most fundamental and critical barrier to “replacement technologies.”
The second hurdle is immune rejection. Whether it’s gene-edited pig organs, stem cells, or bioengineered tissues, the human immune system recognizes them as foreign and launches a strong attack. Current solutions primarily involve reducing antigens through gene editing combined with lifelong immunosuppressive drugs—but these drugs significantly increase the risks of infection and cancer, and their long-term side effects are difficult to avoid. Even if acute rejection is reduced, chronic rejection remains an unsolved challenge.
The third barrier, and the most insidious one: age assimilation. The study in *Aging Cell* repeatedly highlights that scientists are concerned that even if a young organ is successfully transplanted, it will rapidly be "assimilated" by the aging environment of the older body. Exposure to aged plasma, chronic inflammatory factors, and paracrine signals from senescent cells can lead to signs of aging within just a few years—like installing new parts into an old machine, which quickly wear down.
In addition, ethical controversies, high costs, and regulatory gaps also hinder the implementation of "replacement technology" products. However, these bottlenecks are not endpoints, but starting points for breakthroughs.
The ultimate goal of "replacement technology" is to free humanity from the pain, weakness, and diseases caused by aging, thereby maximizing healthy, autonomous, and dignified years of life. From wooden prosthetics 3,000 years ago to today’s gene-edited hearts, humanity’s determination to combat aging has never wavered. In the future, “replacing the heart, replacing the liver, replacing youth” may no longer be science fiction, but an accessible health option for ordinary people.