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Fibrin-genipin annulus fibrosus sealant as a delivery system for anti-TNFα drug

Overview of attention for article published in Spine Journal, September 2015
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Title
Fibrin-genipin annulus fibrosus sealant as a delivery system for anti-TNFα drug
Published in
Spine Journal, September 2015
DOI 10.1016/j.spinee.2015.04.026
Pubmed ID
Authors

Morakot Likhitpanichkul, Yesul Kim, Olivia M. Torre, Eugene See, Zepur Kazezian, Abhay Pandit, Andrew C. Hecht, James C. Iatridis

Abstract

Intervertebral discs (IVD) are attractive targets for local drug delivery because they are avascular structures with limited transport. Painful IVDs are in a chronic inflammatory state. While anti-inflammatories show poor performance in clinical trials their efficacy treating IVD cells suggests that sustained, local drug delivery directly to painful IVDs may be beneficial. To determine if genipin crosslinked fibrin (FibGen) with collagen type I hollow spheres (CHS) can serve as a drug delivery carrier for the anti-TNFα drug, infliximab. Infliximab was chosen as a model drug because of the known role of TNFα in increasing downstream production of several pro-inflammatory cytokines and pain mediators. FibGen was used as drug carrier because it is adhesive injectable, slowly degrading hydrogel with potential to seal annulus fibrosus (AF) defects. CHS allow simple and non-damaging drug loading and could act as a drug reservoir to improve sustained delivery. Biomaterials and human AF cell culture study to determine drug release kinetics and efficacy. Infliximab was delivered at low and high concentrations using FibGen with and without CHS. Gels were analyzed for structure, drug release kinetics, and efficacy treating human AF cells following release. This work was funded by grants from the NIAMS/NIH (R01 AR057397), AO Foundation, and from the Icahn School of Medicine at Mount Sinai. Fibrin showed rapid infliximab drug release but degraded quickly. CHS alone showed a sustained release profile but the small spheres may not remain in a degenerated IVD with fissures. FibGen showed steady and low levels of infliximab release that was increased when loaded with higher drug concentrations. Infliximab was bound in CHS when delivered within FibGen and was only released following enzymatic degradation. The infliximab released over 20 days retained its bioactivity as confirmed by the sustained reduction of IL-1β, IL-6, IL-8, and TNFα concentrations produced by AF cells. Direct mixing of infliximab into FibGen was the simplest drug loading protocol capable of sustained release. Results show feasibility of using drug-loaded FibGen for delivery of infliximab and, in the context with the literature, show potential to seal AF defects and partially restore IVD biomechanics. Future investigations are required to determine if drug-loaded FibGen can effectively deliver drugs, seal AF defects, and promote IVD repair or prevent further IVD degeneration in vivo.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 2%
Unknown 43 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 23%
Student > Doctoral Student 8 18%
Other 8 18%
Researcher 5 11%
Student > Master 4 9%
Other 9 20%
Readers by discipline Count As %
Medicine and Dentistry 13 30%
Agricultural and Biological Sciences 11 25%
Engineering 8 18%
Materials Science 5 11%
Biochemistry, Genetics and Molecular Biology 4 9%
Other 3 7%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 April 2015.
All research outputs
#10,901,569
of 12,301,875 outputs
Outputs from Spine Journal
#2,328
of 2,573 outputs
Outputs of similar age
#189,197
of 226,794 outputs
Outputs of similar age from Spine Journal
#161
of 184 outputs
Altmetric has tracked 12,301,875 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,573 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.8. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 226,794 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 184 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.