Evidence map›Paper›PMID 34968011›Full record

ArticleAdvanced healthcare materials2022

Engineered Cell-Secreted Extracellular Matrix Modulates Cell Spheroid Mechanosensing and Amplifies Their Response to Inductive Cues for the Formation of Mineralized Tissues.

Tomas Gonzalez-Fernandez, Alejandro J Tenorio, Augustine M Saiz, J Kent Leach

Open access · bronzeAbstract read
In one paragraph

Article in Advanced healthcare materials, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
5.1field-weighted citation impact, top 3% of its field
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

47 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Engineering Multi-Spheroid Bone Constructs Through the Fusion of Large MSC Spheroids.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026
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  7. TheMaterials today. Bio · 2026
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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

4 authors at 2 institutions in 1 country.

Tomas Gonzalez-FernandezDepartment of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, 95817, USA.
Alejandro J TenorioDepartment of Biomedical Engineering, University of California, Davis, Davis, CA, 95616, USA.
Augustine M SaizDepartment of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, 95817, USA.
J Kent LeachDepartment of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, 95817, USA.ORCID 0000-0002-1673-3335
UC Davis Health · USUniversity of California, Davis · US

Funding

Identifying the superior ossification pathway for tissue engineered approaches to long bone repairR01AR079211 · NIAMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEACH, J. KENT · 2021 to 2025
$1.9M
Biomaterial regulation of cell spheroids to synergistically enhance bone healingR01DE025475 · NIDCR · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEACH, J. KENT · 2015 to 2019
$1.9M
Engineering the innate immune response to Staphaureus infectionR01AI129302 · NIAID · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEACH, J. KENT, SIMON, SCOTT IRWIN · 2017 to 2021
$1.9M
NIAID NIH HHS R01 AI129302NIAMS NIH HHS R01 AR079211NIDCR NIH HHS R01 DE025475
6 · The paper itself

Abstract

The clinical translation of mesenchymal stromal cell (MSC)-based therapies remains challenging due to rapid cell death and poor control over cell behavior. Compared to monodisperse cells, the aggregation of MSCs into spheroids increases their tissue-forming potential by promoting cell-cell interactions. However, MSCs initially lack engagement with an endogenous extracellular matrix (ECM) when formed into spheroids. Previously the instructive nature of an engineered, cell-secreted ECM is demonstrated to promote survival and differentiation of adherent MSCs. Herein, it is hypothesized that the incorporation of this cell-secreted ECM during spheroid aggregation would enhance MSC osteogenic potential by promoting cell-matrix and cell-cell interactions. ECM-loaded spheroids contained higher collagen and glycosaminoglycan content, and MSCs exhibited increased mechanosensitivity to ECM through Yes-associated protein (YAP) activation via integrin α2β1 binding. ECM-loaded spheroids sustained greater MSC viability and proliferation and are more responsive to soluble cues for lineage-specific differentiation than spheroids without ECM or loaded with collagen. The encapsulation of ECM-loaded spheroids in instructive alginate gels resulted in spheroid fusion and enhanced osteogenic differentiation. These results highlight the clinical potential of ECM-loaded spheroids as building blocks for the repair of musculoskeletal tissues.

Indexed as

CuesOsteogenesisCell DifferentiationCells, CulturedCollagenExtracellular MatrixSpheroids, CellularCollagenextracellular matrixmesenchymal stromal cellsspheroids

Identifiers

PMID34968011
PMCPMC9117430
OpenAlexW4200352330

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.