Evidence map›Paper›PMID 41841213›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Cellular Snowballing: Cell Adhesion and Migration Drive the Self-Assembly of Cell-Microgel Biohybrid Spheroids.

Zaman Ataie, Sina Kheirabadi, Changhao Li, Aneesh Risbud, Aswathy Sebastian, Istvan Albert, Sulin Zhang, Amir Sheikhi

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Zaman AtaieDepartment of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA.
Sina KheirabadiDepartment of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA.
Changhao LiDepartment of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania, USA.
Aneesh RisbudDepartment of Biomedical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA.
Aswathy SebastianHuck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania, USA.
Istvan AlbertDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.
Sulin ZhangDepartment of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania, USA.
Amir SheikhiDepartment of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA.ORCID https://orcid.org/0000-0002-4495-6675

Funding

College of Engineering Diefender for Graduate Fellowship in EntrepreneurshipDorothy Foehr Huck and J. Lloyd Huck Early Career Chair, Huck Institutes of the Life SciencesHuck Institutes of the Life SciencesMaterials Research Institute (MRI) 2022 seed grant for the Convergent Research at the Intersection of Materials-Life-Health-EnvironmentMaterials Research Institute (MRI), The Pennsylvania State UniversityMax M. Snyder Graduate Scholarship in EngineeringMeghan Rose Bradley FoundationThe College of Engineering Materials Matter at the Human Level seed grantsThe National Heart, Lung, and Blood Institute of the National Institutes of Health R01HL167939The Vice Provost and Dean of the Graduate School Student Persistence Scholarship
6 · The paper itself

Abstract

Creating three-dimensional (3D) tissue models using cell spheroids that recapitulate the complicated structures and functions of human tissues is essential for advancing new approach methodologies used in drug testing/screening, disease modeling, and regenerative medicine. However, cell spheroids often have dense cellular structures and subsequently poor cell survival, primarily due to impaired oxygen and metabolite transport. To overcome these limitations, we develop biohybrid spheroids (BHS), self-assembled living-synthetic hybrid aggregates, using adherent cells as assembly engines and hydrogel microparticles (microgels) as extracellular matrix-mimetic substrates. We show the revolving assembly of 3D BHS, driven by progressive cell migration and adhesion via culturing adherent mammalian cells and gelatin methacryloyl microgels, reminiscing a snowballing effect. The aggregation kinetics and terminal size of BHS are tailored by adjusting microgel size and cell-to-microgel ratio. Notably, microgels significantly larger than the cells yield porous, millimeter-sized BHS, facilitating molecular diffusion and improving cell viability. Furthermore, transcriptional analyses show shifts in adhesion, angiogenesis, hypoxia, and proliferation programs in BHS compared with cell spheroids. An agent-based model is developed to recapitulate the snowballing assembly in a geometrically unconstrained environment, providing fundamental insights into the assembly kinetics and the ultimate BHS size and pore features. BHS may open new opportunities for developing predictive and scalable technologies to self-assemble large-scale physiologically relevant tissue models in vitro, potentially transforming the biofabrication of microphysiological systems.

Indexed as

Cell AdhesionCell MovementMicrogelsSpheroids, CellularTissue EngineeringAnimalsCell SurvivalHumansHydrogelsHydrogelsMicrogelsgranular hydrogelliving materialmicrogelnew approach methodologiesspheroidtissue engineering

Identifiers

PMID41841213
PMCPMC13248798

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.