Towards Realistic Meat: Vascularized Tissue Constructs

David Bell
Aug 6
12 min read

Updated: Aug 8

Cultivated meat is stepping closer to mimicking what you’d expect from conventional meat by focusing on vascularisation - essential for creating thicker, structured cuts. Without a vascular system, lab-grown meat is limited to thin layers, but emerging methods are tackling this challenge. Here's a quick overview of three key approaches:

Decellularised Scaffolds: Use plant or animal tissue frameworks to support cell growth, retaining natural structures.
3D Bioprinting: Builds precise vascular networks layer by layer using bioinks.
Co-Culture with Endothelial Cells: Encourages cells to self-organise into functional tissue structures.

Each method has benefits and challenges, with scalability and cost being major hurdles. Combining these techniques could lead to lab-grown meat that looks, cooks, and tastes like the meat you’re used to - all without involving livestock. Read on to explore how these methods work and their potential for commercial production.

1. Decellularised Scaffolds

Decellularised scaffolds offer a fascinating approach to producing vascularised cultivated meat by using the natural structure of existing tissues. This technique involves stripping cells from plant or animal tissues while keeping the extracellular matrix (ECM) intact. The ECM serves as the foundational framework that supports the tissue's original structure.

Mechanism of Vascularisation

Decellularisation transforms plant tissues into functional scaffolds that retain their natural vascular networks. For instance, raw asparagus samples initially contained an average DNA content of 978 ± 62 ng/mg, but after undergoing decellularisation, the DNA content dropped significantly to 254 ± 60 ng/mg[1]. Micro-CT analysis further highlights the efficiency of this process, showing that decellularised plant scaffolds (DPS) achieve about 93.5% porosity with a connectivity value of 93.55%[1]. These porous structures are essential for delivering nutrients and oxygen to muscle and fat cells as they grow. This natural vascular design provides a solid foundation for integrating these cells effectively.

Integration with Muscle and Fat Tissues

The nutrient channels in decellularised scaffolds promote organised cell growth. The success of this integration depends on the type of plant used. For example:

Primary bovine satellite cells grown on decellularised spinach leaves showed 99% viability and achieved 25% differentiation compared to cells grown on gelatin-coated glass slides.
Decellularised parsley scaffolds supported C2C12 myoblast proliferation and differentiation by forming distinct longitudinal and transverse pore structures.
Decellularised celery scaffolds encouraged chicken myoblast growth so effectively that mature myoblasts fully covered the surface and formed fibre-like myotube structures[2].

This adaptability allows researchers to select scaffold types based on the specific needs of different tissues, helping to replicate the texture and structure of conventional meat.

Scalability

Plant-based decellularised scaffolds hold great potential for large-scale meat production. They can be made from a variety of edible plants and shaped into different forms, making them suitable for various bioreactor setups used in cultivating meat[1]. The porous networks in these scaffolds facilitate the flow of nutrients and oxygen, which is critical for growing muscle tissue. However, optimising these porous structures for efficient media perfusion on a commercial scale remains a challenge. Researchers are exploring ways to tailor scaffold sizes or use bottom-up assembly techniques to mimic standard meat cuts. Additionally, plant-derived scaffolds are cost-efficient and naturally replicate the fibrous texture of traditional meat[2].

Readiness for Commercialisation

Despite their promise, decellularised scaffolds face hurdles before they can be widely commercialised. Achieving complete decellularisation and ensuring the removal of surfactant residues are critical steps[1]. While DPS has shown success in aligning muscle cells and producing structured cultivated meat resembling traditional cuts, earlier scaffold methods, such as those using textured soy protein, often suffered from partial degradation, brittleness, and reduced tensile strength when cultured with bovine satellite cells[1]. Future efforts should focus on developing safer surfactants and refining food-grade decellularisation processes to ensure the scaffolds maintain their structural integrity. Another challenge lies in the limited thickness of edible scaffolds, as seen with decellularised spinach leaves and grass. Constructing larger meat samples may require stacking multiple layers, which adds complexity to the process[1].

2. 3D Bioprinting of Vascular Networks

Building on the groundwork laid by decellularised scaffold techniques, 3D bioprinting offers a precise method for creating vascular networks. This technology works by depositing bioinks - combinations of living cells and biomaterials - layer by layer, constructing structures that mimic the intricate architecture of natural meat.

Mechanism of Vascularisation

In 3D bioprinting, bioinks are extruded into supportive hydrogels, forming complex, multi-layered structures capable of delivering essential nutrients and oxygen to the tissue[3][4].

A notable technique, tendon-gel integrated bioprinting (TIP), facilitates the creation of cell fibres that can differentiate into components such as muscle, fat, and capillaries[5]. This method allows for precise engineering of tissues, closely replicating the texture and composition of conventional meat[3].

Kang et al. demonstrated this concept by successfully fabricating meat-like tissues using bioprinting to combine three types of bovine cell fibres: muscle, fat, and vascular tissues[3]. Their work highlights how bioprinting can replicate the structural complexity of traditional meat.

Integration with Muscle and Fat Tissues

One of the biggest challenges in bioprinting is combining vascular networks with muscle and fat tissues while maintaining the texture and functionality of real meat. Studies show that muscle-like stiffness, which ranges between 2–12 kPa, supports the expansion of muscle progenitor cells, a critical step in replicating meat structure[9].

In April 2025, researchers at The University of Tokyo made a significant leap by creating centimetre-scale chicken skeletal muscle tissues. Using a Hollow Fibre Bioreactor (HFB) equipped with 50 hollow fibres, they scaled up to a robot-assisted assembly system with 1,125 fibres. This effort resulted in whole-cut chicken meat, weighing over 10 grams, produced from chicken fibroblast cells[10].

"Our study presents a scalable, top-down strategy for producing whole-cut cultured meat using a perfusable hollow fibre bioreactor... This system enables cell distribution, alignment, contractility, and improved food-related properties." - Shoji Takeuchi, Senior Author, The University of Tokyo[10]

Scalability

Scaling up 3D bioprinted meat production remains a significant challenge. The current process is both slow and costly, requiring advancements in bioprinting speed, efficiency, and cost reduction to reach commercial viability[6].

Some companies are already tackling these issues. Revo Foods in Austria and Redefine Meat in Israel have developed bioprinted meat products by using multiple printheads to layer muscle and fat components in filament-like configurations[3]. These approaches show promise for scaling production while maintaining quality.

Artificial intelligence plays a crucial role in addressing scalability by enabling adaptive modelling and optimisation across the cellular agriculture process[6]. Given the projected 72% increase in global meat demand by 2030 compared to 2000, these technological innovations are essential[6]. Improvements in print speed and cost efficiency are paving the way for broader adoption.

"By offering 3D printing production methodologies to B2B clients, Steakholder Foods has the opportunity to become a backbone supplier that enables the production of products that consumers seek and expect. Our 3D bio-printing technology and customised bio-inks reflect our commitment to revolutionising the food industry." - Arik Kaufman, CEO of Steakholder Foods[8]

Readiness for Commercialisation

Despite its potential, 3D bioprinting of vascular networks still faces hurdles before it can be widely commercialised. While creating vascular tissues from stem cells has been achieved on a small scale, scaling this up remains a challenge[4]. A 2020 survey by GFI and TurtleTree Scientific found that only four out of nineteen cultivated meat companies planned to produce vascular cells within a year[4].

To succeed, the technology must overcome consumer scepticism, improve cost-effectiveness, and ensure safety and quality standards[6]. Key areas of focus include optimising animal cell culture conditions, developing serum-free media, and refining bioreactor designs to meet nutritional standards and gain consumer trust[6].

Endothelial cells, known for their self-organising abilities and role in maintaining scaffold integrity, offer clear benefits for cultivated meat production. However, the additional complexity of co-culturing these cells must be justified by their advantages[4]. Achieving this balance will be critical for the commercial success of bioprinted vascular networks. Both scaffold-based and bioprinting approaches remain essential for replicating the intricate vascularisation needed to match the structure of traditional meat.

3. Co-Culture with Endothelial Cells

Pairing endothelial cells with muscle cells in a co-culture setting allows for the development of functional vascular networks in cultivated meat. This technique taps into the natural ability of cells to self-organise, resulting in tissue structures that bear a closer resemblance to traditional meat.

Mechanism of Vascularisation

The process mirrors how tissues form during embryonic development. Both endothelial and muscle cells are derived from the same presomitic mesoderm (PSM) cell population. To achieve this, a specific protocol is followed: the BMP inhibitor DMH1 is maintained in the culture medium, while angiogenic factors like VEGF and forskolin are introduced. These factors encourage the differentiation of endothelial cells alongside muscle cells. The result is a well-organised endothelial network that penetrates deeply into the tissue, ensuring effective oxygen and nutrient delivery. Impressively, the intercapillary distance in these tissues is about 100 μm [11]. This precise network formation provides a strong foundation for integrating muscle cells into the construct.

Integration with Muscle Tissues

Once the vascular framework is established, muscle tissues integrate smoothly. Within the developing tissue, skeletal muscle domains become surrounded by endothelial cells. By day 15, these muscle domains reach diameters of 200 to 300 μm - an ideal size that supports nutrient diffusion and cell survival [11]. Research by Sanaki-Matsumiya et al. demonstrated how bovine embryonic stem cells could co-induce skeletal muscle, neuronal, and endothelial cells. This approach led to the self-organisation of muscle tissues with both vascularisation and innervation [11]. Notably, achieving this co-induction without genetic modification marks a significant step towards producing structured beef steaks that closely mimic the complexity of conventional meat.

Scalability

Scaling up co-culture systems presents challenges, including biological variability and the need for precise control over timing and conditions during production. A major obstacle remains the absence of fully developed blood vessels, which limits the ability to create larger, mature tissue constructs. However, the natural self-organisation of endothelial cells offers a potential solution, as it could improve vascular distribution in thicker tissues.

Readiness for Commercialisation

Unlike methods such as scaffolding or bioprinting, co-culture relies on the innate programming of cells to replicate the structure of natural meat. This approach has strong potential for commercial use, as it avoids complex machinery and genetic modifications while leveraging biological processes. The formation of uniform vascular networks not only aids regulatory approval but also appeals to consumers. Additionally, since endothelial cells primarily originate from the lateral plate mesoderm, with contributions from the presomitic mesoderm and somites, the method aligns with established developmental pathways. However, ensuring consistent production of large, mature tissues will require robust quality control to address biological variability effectively.

Advantages and Disadvantages

After diving into decellularised scaffolds, bioprinting, and co-culture techniques, let's take a closer look at their strengths and weaknesses. Each method brings something unique to the table, but none are without challenges when it comes to creating realistic cultivated meat.

Decellularised Scaffolds offer a strong starting point by preserving the natural extracellular matrix found in traditional meat. This provides a familiar texture and gives cells a solid structure to attach to and grow within a three-dimensional space. However, these scaffolds struggle with thicker tissue constructs because they lack the intricate vascular networks needed to deliver oxygen and nutrients effectively. With oxygen diffusion limits of around 200 μm, they’re not suitable for creating thicker cuts of meat.

3D Bioprinting of Vascular Networks shines when it comes to precision. It allows researchers to design and position vascular channels exactly where they’re needed, mimicking the complex networks found in natural meat. But this method comes with steep costs and scalability issues. The equipment is expensive, the process takes time, and production requires controlled environments, making it a challenge to scale up economically.

Co-Culture with Endothelial Cells takes advantage of cells’ natural ability to self-organise into vascular networks. This approach reduces the need for complex machinery and could be a more cost-efficient option for large-scale production. However, biological variability can make it difficult to achieve consistent results, and incomplete blood vessel development limits the creation of larger, mature tissue structures.

Despite these differences, all three methods aim to replicate the vascular complexity found in traditional meat. Here’s a side-by-side comparison of their key features:

Method	Mechanism	Scalability	Integration with Muscle/Fat	Commercialisation Readiness
Decellularised Scaffolds	Natural ECM preservation	Moderate – limited by scaffold availability	Strong texture replication	High – established processing methods
3D Bioprinting	Precise network design	Low – equipment and time intensive	Good control over placement	Low – high costs and complexity
Co-Culture	Cell self-organisation	High – leverages natural processes	Good integration with muscle and fat tissues	Moderate – variability requires quality control

The choice of method depends on balancing cost and functionality. For bulk meat production, scaffold vascularisation or active perfusion techniques may be necessary to ensure cells receive enough nutrients and oxygen. Without this, cell viability can suffer due to shear stress[12]. Hybrid approaches, such as adding perfusion channels to scaffolds, are also being explored to combine the strengths of different methods while addressing their individual shortcomings.

Another key factor is consumer acceptance. Techniques that produce meat closely resembling traditional products in texture and structure are more likely to win over consumers, who often prefer familiar appearances and experiences.

Each approach tackles the challenge of vascularisation differently - whether by using natural structures, engineering precise solutions, or leaning on the cells’ natural abilities. The future of cultivated meat may lie in combining these methods, tailoring them to specific products and market needs. Striking the right balance between these trade-offs will be crucial for creating cultivated meat that’s both realistic and commercially viable.

Conclusion

Creating realistic cultivated meat hinges on achieving effective vascularisation, which is essential for bridging the gap between lab-grown and conventional meat. Among the various techniques explored, co-culture with endothelial cells shows particular promise.

Decellularised scaffolds stand out for their ability to replicate natural meat texture. Research indicates that uncooked prototypes can match pork loin in most textural aspects[1]. However, these scaffolds are better suited for thinner cuts and may fall short when it comes to producing the thicker cuts consumers often prefer.

3D bioprinting offers a different advantage: precision. This technique enables the creation of intricate vascular networks, which are crucial for scaling up tissue engineering efforts[13].

Co-culture takes a self-organising approach, using endothelial cells to keep scaffold pores open and tackle some of the most pressing challenges in tissue engineering[4]. Industry confidence in this method is growing. A recent survey revealed that four out of nineteen cultivated meat manufacturers plan to integrate endothelial or other vascular cells within the next year[4].

Hybrid methods could hold the key to unlocking the full potential of cultivated meat. For example, in 2022, Zagury et al. demonstrated how separate alginate-based constructs containing muscle and fat cells could be combined into cohesive structures. This modular approach shows promise for scaling production effectively[4].

These advancements in vascularised tissue engineering are more than just technical milestones. They represent a step towards a food system that produces real meat without the need for animal slaughter. The Cultivarian Society envisions a future where cultivated meat not only satisfies consumer demand but also reduces the environmental footprint of livestock farming, which currently uses 30% of the planet's ice-free land and contributes 18% of global greenhouse gas emissions[7].

Progress in vascularisation techniques is bringing cultivated meat closer to reality. With improvements in texture, nutrient distribution, and scalable production, this technology is paving the way for a meat experience that feels authentic while promoting a sustainable and ethical food system.

The focus is no longer on whether vascularised cultivated meat can rival traditional meat, but on how quickly these innovations can scale to meet global demand. With ongoing research and investment, that future is well within reach.

FAQs

What are the key challenges in producing vascularised cultivated meat at scale?

Scaling up the production of vascularised cultivated meat comes with its fair share of hurdles. Key issues include high production costs, navigating complex regulatory approvals, and ensuring cell line stability to deliver consistent quality and safety. On the technical side, challenges like achieving proper tissue vascularisation for nutrient delivery, creating cost-effective bioprocessing methods, and avoiding contamination add further layers of complexity.

Addressing these challenges is critical to making cultivated meat an affordable, safe, and practical option for large-scale commercial production. Progress in technology, regulatory policies, and manufacturing techniques will be vital in moving this innovative concept closer to becoming a reality.

How does using endothelial cells in co-culture improve the texture and structure of cultivated meat compared to other methods?

The co-culture method involving endothelial cells enhances the texture and structure of cultivated meat by promoting the formation of vascular networks. These networks play a key role in supporting tissue development, resulting in a fibrous, layered texture that closely resembles traditional meat.

Unlike techniques like extrusion or bioprinting, which rely on scaffolds to shape the tissue, co-culture methods encourage a more natural tissue organisation. This adds a level of complexity to the structure, making the texture and mouthfeel of cultivated meat much closer to that of conventional meat. It’s a step forward in narrowing the gap between lab-grown and farm-raised options.

What environmental advantages does vascularised cultivated meat offer compared to traditional livestock farming?

Cultivated meat with vascularisation offers a dramatic reduction in environmental impact compared to traditional livestock farming. It has the potential to lower greenhouse gas emissions by up to 96%, use 99% less land, and decrease water consumption by 82–96%. These changes play a crucial role in addressing deforestation, protecting natural habitats, and conserving essential water supplies.

With its minimal need for land and water, cultivated meat presents a promising alternative to conventional farming practices, helping to reduce the strain on the planet. This approach aligns with the Cultivarian Society's mission to promote a more compassionate and environmentally conscious food system for future generations.