Evidence map›Paper›PMID 35292368›Full record

ArticleNanomedicine : nanotechnology, biology, and medicine2022

Matrix stiffness regulates lipid nanoparticle-mRNA delivery in cell-laden hydrogels.

Avathamsa Athirasala, Siddharth Patel, Paula P Menezes, Jeonghwan Kim, Anthony Tahayeri, Gaurav Sahay, Luiz E Bertassoni

Open access · greenAbstract read
In one paragraph

Article in Nanomedicine : nanotechnology, biology, and medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

8 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. 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

7 authors at 2 institutions in 2 countries.

Avathamsa AthirasalaDepartment of Biomedical Engineering, Collaborative Life Sciences Building, Oregon Health and Science University, Portland, OR, USA.
Siddharth PatelDepartment of Pharmaceutical Sciences, College of Pharmacy, Collaborative Life Science Building, Oregon State University, Portland, OR, USA.
Paula P MenezesDivision of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, OR, USA; Department of Pharmacy, Federal University of Sergipe, Aracaju, Sergipe, Brazil.
Jeonghwan KimDepartment of Pharmaceutical Sciences, College of Pharmacy, Collaborative Life Science Building, Oregon State University, Portland, OR, USA.
Anthony TahayeriDivision of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, OR, USA.
Gaurav SahayDepartment of Biomedical Engineering, Collaborative Life Sciences Building, Oregon Health and Science University, Portland, OR, USA; Department of Pharmaceutical Sciences, College of Pharmacy, Collaborative Life Science Building, Oregon State University, Portland, OR, USA; Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA.
Luiz E BertassoniDepartment of Biomedical Engineering, Collaborative Life Sciences Building, Oregon Health and Science University, Portland, OR, USA; Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, OR, USA; Center for Regenerative Medicine, Oregon Health and Science University, Portland, OR, USA; Cancer Early Detection Advanced Research (CEDAR) Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA. Electronic address: bertasso@ohsu.edu.
Oregon Health & Science University · USOregon State University · US

Funding

Microengineering vascularized and innervated bone-like scaffolds as an alternative to autologous bone graftsR01DE029553 · NIDCR · OREGON HEALTH & SCIENCE UNIVERSITY · PI BERTASSONI, LUIZ EDUARDO · 2021 to 2025
$3.0M
Microengineering the Dental Pulp Vascular Microenvironment_Diversity SupplementR01DE026170 · NIDCR · OREGON HEALTH & SCIENCE UNIVERSITY · PI BERTASSONI, LUIZ EDUARDO · 2016 to 2020
$2.5M
PORT (Portland Oral health Research Training)T90DE030859 · NIDCR · OREGON HEALTH & SCIENCE UNIVERSITY · PI WU, HUI · 2021 to 2025
$2.1M
PORT (Portland Oral health Research Training)R90DE031533 · NIDCR · OREGON HEALTH & SCIENCE UNIVERSITY · PI WU, HUI · 2021 to 2025
$821k
NIDCR NIH HHS R01 DE026170NIDCR NIH HHS R01 DE029553NIDCR NIH HHS R90 DE031533NIDCR NIH HHS T90 DE030859
6 · The paper itself

Abstract

mRNA therapeutics have increased in popularity, largely due to the transient and fast nature of protein expression and the low risk of off-target effects. This has increased drastically with the remarkable success of mRNA-based vaccines for COVID-19. Despite advances in lipid nanoparticle (LNP)-based delivery, the mechanisms that regulate efficient endocytic trafficking and translation of mRNA remain poorly understood. Although it is widely acknowledged that the extracellular matrix (ECM) regulates uptake and expression of exogenous nano-complexed genetic material, its specific effects on mRNA delivery and expression have not yet been examined. Here, we demonstrate a critical role for matrix stiffness in modulating both mRNA transfection and expression and uncover distinct mechano-regulatory mechanisms for endocytosis of mRNA through RhoA mediated mTOR signaling and cytoskeletal dynamics. Our findings have implications for effective delivery of therapeutic mRNA to targeted tissues that may be differentially affected by tissue and matrix stiffness.

Indexed as

COVID-19NanoparticlesCOVID-19 VaccinesHumansHydrogelsLipidsLiposomesRNA, MessengerCOVID-19 VaccinesHydrogelsLipid NanoparticlesLipidsLiposomesRNA, Messenger3D hydrogelsLNPsMechanotransductionmRNA deliverymTORRhoA

Identifiers

PMID35292368
PMCPMC9206884
OpenAlexW4221053192

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.