Evidence map›Paper›PMID 33409509›Full record

ArticleBiomaterials science2021

BMP-2 delivery strategy modulates local bone regeneration and systemic immune responses to complex extremity trauma.

Casey E Vantucci, Laxminarayanan Krishan, Albert Cheng, Ayanna Prather, Krishnendu Roy, Robert E Guldberg

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 6% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

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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

6 authors at 2 institutions in 2 countries.

Casey E VantucciWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA and Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
Laxminarayanan KrishanParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
Albert ChengParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA and George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Ayanna PratherParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
Krishnendu RoyWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA and Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-9972-0950
Robert E GuldbergKnight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, OR, USA. guldberg@uoregon.edu.ORCID http://orcid.org/0000-0002-0303-261X
Georgia Institute of Technology · USUniversity of Oregon · US

Funding

Immunoengineering Strategies for Musculoskeletal TraumaR01AR074960 · NIAMS · UNIVERSITY OF OREGON · PI GULDBERG, ROBERT E · 2020 to 2024
$2.5M
NIAMS NIH HHS R01 AR074960
6 · The paper itself

Abstract

Bone nonunions arising from large bone defects and composite injuries remain compelling challenges for orthopedic surgeons. Biological changes associated with nonunions, such as systemic immune dysregulation, can contribute to an adverse healing environment. Bone morphogenetic protein 2 (BMP-2), an osteoinductive and potentially immunomodulatory growth factor, is a promising strategy; however, burst release from the clinical standard collagen sponge delivery vehicle can result in adverse side effects such as heterotopic ossification (HO) and irregular bone structure, especially when using supraphysiological BMP-2 doses for complex injuries at high risk for nonunion. To address this challenge, biomaterials that strongly bind BMP-2, such as heparin methacrylamide microparticles (HMPs), may be used to limit exposure and spatially constrain proteins within the injury site. Here, we investigate moderately high dose BMP-2 delivered in HMPs within an injectable hydrogel system in two challenging nonunion models exhibiting characteristics of systemic immune dysregulation. The HMP delivery system increased total bone volume and decreased peak HO compared to collagen sponge delivery of the same BMP-2 dose. Multivariate analyses of systemic immune markers showed the collagen sponge group correlated with markers that are hallmarks of systemic immune dysregulation, including immunosuppressive myeloid-derived suppressor cells, whereas the HMP groups were associated with immune effector cells, including T cells, and cytokines linked to robust bone regeneration. Overall, our results demonstrate that HMP delivery of moderately high doses of BMP-2 promotes repair of complex bone nonunion injuries and that local delivery strategies for potent growth factors like BMP-2 may positively affect the systemic immune response to traumatic injury.

Indexed as

Bone Morphogenetic Protein 2Bone RegenerationCollagenExtremitiesImmunityBone Morphogenetic Protein 2Collagen

Identifiers

PMID33409509
PMCPMC8256799
OpenAlexW3113464241

What Socratic 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 Socratic graph.