Evidence map›Paper›PMID 22687758›Full record

ArticleBiomaterials2012

Hyaluronic acid-based hydrogels functionalized with heparin that support controlled release of bioactive BMP-2.

Gajadhar Bhakta, Bina Rai, Zophia X H Lim, James H Hui, Gary S Stein, Andre J van Wijnen, Victor Nurcombe, Glenn D Prestwich, Simon M Cool

Abstract read
In one paragraph

Article in Biomaterials, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
7.9field-weighted citation impact, top 2% 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

66 citing papers in PubMed, 186 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. The 3-Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  20. Enzymatic Synthesis of Glycans and Glycoconjugates.Advances in biochemical engineering/biotechnology · 2021
    Review

6 more citing papers are in PubMed but not listed here.

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

9 authors at 5 institutions in 2 countries.

Gajadhar BhaktaInstitute of Medical Biology, A*STAR, 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
Bina Rai
Zophia X H Lim
James H Hui
Gary S Stein
Andre J van Wijnen
Victor Nurcombe
Glenn D Prestwich
Simon M Cool
Agency for Science, Technology and Research · SGNational University of Singapore · SGUniversity of Massachusetts Chan Medical School · USInstitute of Medical Biology · SGUniversity of Utah · US

Funding

CONTROL OF OSTEOBLAST PROLIFERATION AND DIFFERENTIATIONR01AR039588 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LIAN, JANE B., STEIN, GARY S. · 1990 to 2019
$8.0M
Molecular Control of Bone FormationR01AR049069 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI WESTENDORF, JENNIFER J · 2003 to 2021
$5.8M
NIAMS NIH HHS R01 AR039588NIAMS NIH HHS R01 AR049069
6 · The paper itself

Abstract

Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive factor, yet its clinical use is limited by a short biological half-life, rapid local clearance and propensity for side effects. Heparin (HP), a highly sulfated glycosaminoglycan (GAG) that avidly binds BMP-2, has inherent biological properties that may circumvent these limitations. Here, we compared hyaluronan-based hydrogels formulated to include heparin (Heprasil™) with similar gels without heparin (Glycosil™) for their ability to deliver bioactive BMP-2 in vitro and in vivo. The osteogenic activity of BMP-2 released from the hydrogels was evaluated by monitoring alkaline phosphatase (ALP) activity and SMAD 1/5/8 phosphorylation in mesenchymal precursor cells. The osteoinductive ability of these hydrogels was determined in a rat ectopic bone model by 2D radiography, 3D μ-CT and histological analyses at 8 weeks post-implantation. Both hydrogels sustain the release of BMP-2. Importantly, the inclusion of a small amount of heparin (0.3% w/w) attenuated release of BMP-2 and sustained its osteogenic activity for up to 28 days. In contrast, hydrogels lacking heparin released more BMP-2 initially but were unable to maintain BMP-2 activity at later time points. Ectopic bone-forming assays using transplanted hydrogels emphasized the therapeutic importance of the initial burst of BMP-2 rather than its long-term osteogenic activity. Thus, tuning the burst release phase of BMP-2 from hydrogels may be advantageous for optimal bone formation.

Indexed as

AnimalsBone Morphogenetic Protein 2FemaleHeparinHyaluronic AcidHydrogelsOsteogenesisRatsRats, Sprague-DawleyTissue EngineeringBone Morphogenetic Protein 2HeparinHyaluronic AcidHydrogels

Identifiers

PMID22687758
PMCPMC3628623
OpenAlexW2005848041

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.