# Living Tissues by Design: The Rise of Hybrid Models in Biofabrication

**Authors:** Varvara Platania, Argyro Lamprou, Isaac Maximiliano Bugueno

PMC · DOI: 10.3390/jfb17030135 · Journal of Functional Biomaterials · 2026-03-10

## TL;DR

Scientists are developing hybrid tissue models that combine self-organizing cells with engineered structures to better mimic human tissues for disease research and drug testing.

## Contribution

The paper introduces recent hybrid biofabrication approaches that integrate organoids and bioprinting to create more physiologically relevant tissues.

## Key findings

- Hybrid models combine self-organizing units with engineered scaffolds to improve tissue complexity.
- Advances in bioink and vascularization techniques enable perfusable, multi-compartment tissues.
- Current challenges include achieving full cellular diversity and reproducibility in hybrid models.

## Abstract

Current in vitro tissue models struggle to recapitulate the structural, vascular, and mechanical complexity of human tissues, limiting their physiological relevance for disease modelling and preclinical testing. Self-organising three-dimensional cultures such as spheroids and organoids capture key aspects of cellular organisation and differentiation, but they commonly lack controlled geometry, perfusable vasculature, and reproducible mechanical microenvironments. Conversely, biofabrication strategies, such as three-dimensional (3D) bioprinting and organ-on-chip (OoC) microfluidic devices, offer spatial control, integrated perfusion, and dynamic mechanical stimulation, yet often fall short in recapitulating the full cellular diversity and self-organisation of native tissues. Notably, emerging hybrid approaches that embed self-organising biological units (e.g., organoids and spheroids) into engineered scaffolds or microfluidic platforms combine biological relevance, architectural fidelity, and functional control. Advances in bioink chemistry, sacrificial-printing vascularisation, and chip–organoid interfaces now enable perfusable, multicompartment tissues suitable for disease modelling and preclinical testing. This review highlights the most recent (2020–2025) progress in organoid vascularisation, bioprinting strategies for prevascularised constructs, and OoC integration, outlining remaining challenges and emphasising priorities for next-generation hybrid cellular and tissue models.

## Full-text entities

- **Genes:** REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, LGR5 (leucine rich repeat containing G protein-coupled receptor 5) [NCBI Gene 8549] {aka FEX, GPR49, GPR67, GRP49, HG38}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** injury to (MESH:D014947), phototoxicity (MESH:D017484), glioblastoma (MESH:D005909), hypoxia (MESH:D000860), avascular tumours (MESH:D009369), hypoxic (MESH:D002534), necrosis (MESH:D009336), breast (MESH:D061325)
- **Chemicals:** ruthenium (MESH:D012428), silicone (MESH:D012828), BioRender (-), polystyrene sulfonate (MESH:C003321), O2 (MESH:D010100), Pluronic (MESH:D020442), PDMS (MESH:C013830), eosin (MESH:D004801), alginate (MESH:D000464), PEDOT:PSS (MESH:C533756), poly(3,4-ethylenedioxythiophene) (MESH:C121383), carbohydrate (MESH:D002241)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13028380/full.md

## References

88 references — full list in the complete paper: https://tomesphere.com/paper/PMC13028380/full.md

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Source: https://tomesphere.com/paper/PMC13028380