Jamming for Healing: How Blood-Derived Proteins Are Shaping the Future of Bioprinting

2 Jul 2025

Blood-derived materials are gaining momentum in regenerative medicine. With their natural ability to support healing, they are emerging as powerful building blocks for therapeutic biomaterials.

In a recent study, researchers from the University of Aveiro (UAVR) in Portugal and its spin-off Metatissue - both partners in the EU-funded InterLynk project collaborated to develop a new approach for transforming blood-derived proteins into 3D-printable inks. Their findings, published in the journal Aggregate in April 2025, mark a major step forward in engineering personalized, patient-compatible scaffolds for tissue repair.

Titled “Nozzle Jamming Granularized Blood-Derived Proteins for Bioprinting Cell-Instructive Architectures,” the paper was led by Lucas Ribeiro and João Rocha Maia, with Rita Sobreiro-Almeida and João Mano as corresponding authors. Co-authors include, Vítor Gaspar, Catarina Custódio, and Emerson Camargo.

 

From Blood to Bioink: Solving a Printability Problem

At the heart of the study lies a common challenge in biofabrication: how to turn biologically rich but low-viscosity substances, like platelet lysates, into materials that can be extruded and shaped without losing their natural healing potential.

Human platelet lysates (PL) are a blood-derived protein mixture obtained from platelets, tiny cell fragments in our blood that play a key role in clotting and wound healing. Rich in growth factors and biologically active molecules, PL have strong potential as a natural ingredient in regenerative medicine. They stimulate cell growth, support tissue repair, and offer an appealing alternative to synthetic materials.

An earlier study within the InterLynk project, published in Advanced Science in 2024, had already made significant progress by developing an ink engineering strategy based on either PL or albumin and their methacrylated counterparts – hPLMA[1] and BSAMA[2] - to improve their viscosity for 3D printing. Methacrylation is a process by which proteins are modified to react to light, allowing them to solidify during the printing process.That approach unlocked new potential for these proteins in tissue engineering.

Building on that foundation, the current study explores the use of PL to produce 3D-printed structures with greater architectural complexity - a known limitation identified in earlier work - by introducing a versatile and highly reproducible granular ink fabrication method. The process starts by forming bulk hydrogels from a mix of modified and unmodified proteins, which are granularized into soft, gel-like microgels using mechanical fragmentation. These microgels are processed through nozzle jamming, a technique that compresses the particles and removes excess water as they pass through the printer nozzle to form a stable, extrudable ink. The result is a printable material that retains the biological properties of blood-derived proteins on printed constructs, while enabling precise control over scaffold shape and complexity by using post-printing photocuring. This was possible due to the photorresponsive moieties, small chemical units that respond to light,that were previously introduced. Watch our short video to see the full process in action.

Printed Scaffolds That Breathe and Heal

What emerged from this approach was more than just a printable ink. The resulting scaffolds exhibited microporosity, allowing cells to migrate and grow between the microgels. When human adipose-derived stem cells (stem cells isolated from fat tissue) were seeded onto these structures - or even mixed directly in bioink formulations - they not only survived but actively proliferated in the interstitial spaces.

Thanks to the growth factor-rich composition of the PL, the ink required no additional supplements or adjuvants to support cell culture. The ink itself served as both a structural matrix and a biological cue.

The team printed a variety of scaffold geometries, including filaments, grids, and more intricate forms, without needing a supporting bath. After light-triggered photocrosslinking, the constructs remained mechanically stable and biologically active over time.

 

Modularity, Drug Delivery, and Personalized Medicine

One of the most compelling outcomes of this study is the ink’s modularity. Because it is made from microgels, the formulation can be tuned - its stiffness, bioactivity, or even drug content can be adjusted before printing. In practical terms, this means the same basic ink could be customized for different tissues, patients, or therapeutic goals.

Need an implant that releases anti-inflammatories over time? A drug-loaded scaffold can be printed on demand. Need a structure stiff enough for bone repair, but gentle enough for soft tissue regeneration? The ink can be tailored for that too.

This adaptability, combined with the use of patient-derived materials, positions the ink as a strong candidate for personalized medicine. By minimizing immune rejection risks and removing dependence on donor tissue or synthetic implants, this approach has the potential to optimize access to cutting-edge regenerative therapies.

 

A Living Scaffold for the Future of Regenerative Medicine

This study represents a meaningful next step in the InterLynk project’s advancement of blood-derived biomaterials for 3D printing, building on earlier work that chemically improved the printability of PL and albumin-based inks.

By applying nozzle jamming to protein-based microgels, the researchers developed a microporous, cell-instructive scaffold with excellent structural integrity and biological performance, plus the added potential for drug delivery and tissue-specific tuning. This method not only enhances print fidelity and flexibility but also brings us closer to the creation of fully personalized, biologically active implants.

By transforming the body’s own regenerative proteins into precisely structured, living materials, this work advances the InterLynk vision of adaptable, patient-specific solutions where biology, engineering, and clinical innovation come together to shape the future of healing.



[1] human Platelet Lysate Methacrylate

[2] Bovine Serum Albumin Methacrylate


Source: Ribeiro, L.S., Rocha Maia, J., Gaspar, V.M., Custódio, C.A., Camargo, E.R., Sobreiro-Almeida, R., Mano, J.F. Nozzle Jamming Granularized Blood-Derived Proteins for Bioprinting Cell-Instructive Architectures. Aggregate, 2025; 0:e70041. https://doi.org/10.1002/agt2.70041

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