Wyss-Led ARPA-H Project Aims to Deliver Universal, Off-the-Shelf Liver Grafts
A multidisciplinary team led by the Wyss Institute at Harvard University has secured a major award from the Advanced Research Projects Agency for Health (ARPA-H) to develop implantable, immune-compatible liver grafts that could transform treatment for liver failure.
Announced in January 2026, the initiative—known as ImPLANT (Immunoshielded Printed Liver Assist NeoOrgan for Transplant)—is backed by up to $25 million over five years under ARPA-H’s PRINT program. Its ambitious goal: engineer transplant-ready liver tissue that can be manufactured at scale and implanted without lifelong immunosuppression.
With more than 2 million deaths annually attributed to liver failure and donor organs in critically short supply, the project targets one of medicine’s most persistent unmet needs.
Rebuilding the Liver from Cells Up
At the center of the program is Christopher Chen, Principal Investigator and Wyss Core Faculty member, who leads a team spanning synthetic biology, biomaterials, immunology, and biomanufacturing.
The approach begins with human induced pluripotent stem cells (iPSCs), which will be programmed using synthetic gene circuits to differentiate into the full range of liver-specific cell types. Researchers at Massachusetts Institute of Technology are developing these genetic control systems to guide multi-step, branched differentiation pathways.
Once generated, these cells will be immunoengineered to evade immune rejection—an essential step toward creating “universal donor” tissues suitable for broad patient populations.
From Organoids to Organ-Scale Constructs
The ImPLANT team will assemble differentiated cells into liver organoids and then scale them into vascularized tissue constructs. This process integrates:
- Advanced 3D bioprinting of living tissues
- Engineered biomaterial scaffolds
- Perfusion-enabled bioreactors
- Controlled maturation environments
A core technical challenge is vascularization. Without dense, functional blood vessel networks, large tissue constructs cannot survive or perform metabolic functions. Chen’s group is applying its expertise in vascular biology to embed perfusable networks that support nutrient exchange, toxin metabolism, and protein synthesis.
Meanwhile, biomaterials specialists are developing printable hydrogels and scaffolds that guide tissue architecture while supporting long-term cell viability.
Engineering Immune Tolerance
Beyond structural complexity, transplant rejection remains a central barrier. Even closely matched donor organs often trigger immune responses that require lifelong suppression.
ImPLANT addresses this through integrated immunoengineering and validation studies led by transplant experts at Columbia University. The team will test engineered tissues in:
- Humanized immune system mouse models
- Large animal transplant models
- Disease-specific challenge environments
These studies aim to verify not only immune tolerance, but also metabolic performance, durability, and safety under clinically relevant conditions.
If successful, the platform could establish a new paradigm for immune-compatible engineered organs.
Bioreactors and GMP-Ready Manufacturing
Scaling liver tissue from laboratory prototypes to clinical products requires industrial-grade manufacturing systems. To address this, the project integrates advanced bioreactor design with chemistry, manufacturing, and controls (CMC) development.
Next-generation bioreactors will:
- Precisely regulate oxygen, nutrients, and mechanical cues
- Support organoid and tissue maturation
- Enable transport and preservation
- Generate data for regulatory submissions
These systems are intended to form the foundation for future GMP facilities capable of producing standardized, off-the-shelf liver grafts.
A Platform, Not Just a Product
While ImPLANT is focused on liver failure, its broader significance lies in platform development.
By combining:
- Programmable stem cells
- Immune cloaking strategies
- Vascularized bioprinting
- Scalable biomanufacturing
the project is building a modular framework that could extend to other solid organs in the future.
For the biofabrication sector, this represents a shift from bespoke, patient-specific constructs toward standardized, inventory-ready biological implants—closer to how medical devices and biologics are produced today.
Implications for the Biofabrication Ecosystem
ImPLANT reflects a growing convergence of disciplines that are redefining organ engineering:
| Domain | Contribution |
|---|---|
| Synthetic Biology | Programmable differentiation and immune evasion |
| Biomaterials | Printable, instructive scaffolds |
| Bioprinting | High-resolution tissue assembly |
| Vascular Engineering | Perfusable networks |
| Biomanufacturing | GMP-aligned scale-up |
By aligning these capabilities under one coordinated program, ARPA-H is accelerating translation timelines that traditionally span decades.
For startups, investors, and translational researchers, the project offers a preview of what “industrialized organ fabrication” may look like in the next decade.
From Moonshot to Market
As Chen noted in announcing the award, ImPLANT represents a “moonshot” enabled by recent advances in regenerative medicine and manufacturing science. Yet unlike earlier organ engineering efforts, this program embeds regulatory, manufacturing, and scalability considerations from the outset.
With ARPA-H’s milestone-driven funding model and close integration of academic and translational partners, ImPLANT is designed to move rapidly from proof-of-concept to clinic-ready systems.
If successful, it could redefine how end-stage organ failure is treated—replacing donor scarcity with engineered abundance.
Bottom Line
The Wyss-led ImPLANT program marks one of the most comprehensive efforts to date to industrialize liver biofabrication. By uniting synthetic biology, immunoengineering, vascularized bioprinting, and scalable manufacturing under a single initiative, the project moves the field closer to universal, off-the-shelf organ replacement.
For the biofabrication industry, this is not just a research milestone—it is a blueprint for how complex living products may ultimately reach patients at scale.
Original article here.
The Business of Biofabrication 
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