Evidence map›Paper›PMID 33385687›Full record

ArticleBiomaterials2021

Hydrogel mechanics are a key driver of bone formation by mesenchymal stromal cell spheroids.

Jacklyn Whitehead, Katherine H Griffin, Marissa Gionet-Gonzales, Charlotte E Vorwald, Serena E Cinque, J Kent Leach

Open access · greenAbstract read
In one paragraph

Article in Biomaterials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
6.3field-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

43 citing papers in PubMed, 88 citations in OpenAlex.

  1. Review
  2. Edible Sulfonated Soy Protein Microcarriers for Cultivated Meat Cell Expansion.Journal of biomedical materials research. Part A · 2026
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  10. Revolutionizing bone healing: the role of 3D models.Cell regeneration (London, England) · 2025
    Review
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  12. Article
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  19. Article
  20. Stem Cells and Bone Tissue Engineering.Life (Basel, Switzerland) · 2024
    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

6 authors at 1 institution in 1 country.

Jacklyn WhiteheadDepartment of Biomedical Engineering, University of California, Davis, CA, 95616, USA.
Katherine H GriffinDepartment of Biomedical Engineering, University of California, Davis, CA, 95616, USA; School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
Marissa Gionet-GonzalesDepartment of Biomedical Engineering, University of California, Davis, CA, 95616, USA.
Charlotte E VorwaldDepartment of Biomedical Engineering, University of California, Davis, CA, 95616, USA.
Serena E CinqueDepartment of Biomedical Engineering, University of California, Davis, CA, 95616, USA.
J Kent LeachDepartment of Biomedical Engineering, University of California, Davis, CA, 95616, USA; Department of Orthopaedic Surgery, UC Davis Health, Sacramento, CA, 95817, USA. Electronic address: jkleach@ucdavis.edu.
University of California, Davis · US

Funding

Training Program In Basic & Translational Cardiovascular ScienceT32HL086350 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Martin Cadeiras, David A. Liem · 2008 to 2026
$7.1M
Dual peptide presentation from bioengineered carriers to potentiate stromal cell function and tissue repairR01DE025899 · NIDCR · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEACH, J. KENT · 2017 to 2021
$2.5M
UC Davis DVM/PhD Medical Scientist Training ProgramT32GM136559 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Xinbin Chen, Bethany Paige Cummings · 2020 to 2026
$2.2M
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
NHLBI NIH HHS T32 HL086350NIAID NIH HHS R01 AI129302NIDCR NIH HHS R01 DE025475NIDCR NIH HHS R01 DE025899NIGMS NIH HHS T32 GM136559
6 · The paper itself

Abstract

Mesenchymal stromal cells (MSCs) can promote tissue repair in regenerative medicine, and their therapeutic potential is further enhanced via spheroid formation. Stress relaxation of hydrogels has emerged as a potent stimulus to enhance MSC spreading and osteogenic differentiation, but the effect of hydrogel viscoelasticity on MSC spheroids has not been reported. Herein, we describe a materials-based approach to augment the osteogenic potential of entrapped MSC spheroids by leveraging the mechanical properties of alginate hydrogels. Compared to spheroids entrapped in covalently crosslinked elastic alginate, calcium deposition of MSC spheroids was consistently increased in ionically crosslinked, viscoelastic hydrogels. We previously demonstrated that intraspheroidal presentation of Bone Morphogenetic Protein-2 (BMP-2) on hydroxyapatite (HA) nanoparticles resulted in more spatially uniform MSC osteodifferentiation, providing a method to internally influence spheroid phenotype. In these studies, we observed significant increases in calcium deposition by MSC spheroids loaded with BMP-2-HA in viscoelastic gels compared to soluble BMP-2, which was greater than spheroids entrapped in all elastic alginate gels. Upon implantation in critically sized calvarial bone defects, bone formation was greater in all animals treated with viscoelastic hydrogels. Increases in bone formation were evident in viscoelastic gels, regardless of the mode of presentation of BMP-2 (i.e., soluble delivery or HA nanoparticles). These studies demonstrate that the dynamic mechanical properties of viscoelastic alginate are an effective strategy to enhance the therapeutic potential of MSC spheroids for bone formation and repair.

Indexed as

Mesenchymal Stem CellsOsteogenesisAnimalsCell DifferentiationHydrogelsSpheroids, CellularHydrogelsAlginateBone regenerationMesenchymal stromal cellsSpheroidsStress relaxation

Identifiers

PMID33385687
PMCPMC7870573
OpenAlexW3118001127

What OpenQuestion holds

Textmetadata
LicenceTDM
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.