ArticleJournal of controlled release : official journal of the Controlled Release Society2010
Device-based local delivery of siRNA against mammalian target of rapamycin (mTOR) in a murine subcutaneous implant model to inhibit fibrous encapsulation.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics.Frontiers in bioengineering and biotechnology · 2021Pooled it
- Don't judge an implant by its cover: how the foreign body response and fibrotic capsule might be harnessed for good.npj biomedical innovations · 2026Review
- Smart and Biodegradable Polymers in Tissue Engineering and Interventional Devices: A Brief Review.Polymers · 2025Review
- Modulating Myofibroblastic Differentiation of Fibroblasts through Actin-MRTF Signaling Axis by Micropatterned Surfaces for Suppressed Implant-Induced Fibrosis.Research (Washington, D.C.) · 2023Article
- Localized, on-demand, sustained drug delivery from biopolymer-based materials.Expert opinion on drug delivery · 2022Article
- Implant Fibrosis and the Underappreciated Role of Myofibroblasts in the Foreign Body Reaction.Cells · 2021Review
- Dielectric Elastomer Actuators, Neuromuscular Interfaces, and Foreign Body Response in Artificial Neuromuscular Prostheses: A Review of the Literature for an In Vivo Application.Advanced healthcare materials · 2021Review
- Biodegradable Stent with mTOR Inhibitor-Eluting Reduces Progression of Ureteral Stricture.International journal of molecular sciences · 2021Article
- Hydrogel-Based Localized Nonviral Gene Delivery in Regenerative Medicine Approaches-An Overview.Pharmaceutics · 2020Review
- Mineralized collagen-modified PMMA cement enhances bone integration and reduces fibrous encapsulation in the treatment of lumbar degenerative disc disease.Regenerative biomaterials · 2020Article
- Domesticating the foreign body response: Recent advances and applications.Advanced drug delivery reviews · 2019Review
- Bioreducible Poly(Amino Ethers) Based mTOR siRNA Delivery for Lung Cancer.Pharmaceutical research · 2018Article
- Photocrosslinkable, biodegradable hydrogels with controlled cell adhesivity for prolonged siRNA delivery to hMSCs to enhance their osteogenic differentiation.Journal of materials chemistry. B · 2017Article
- Invasive Intraneural Interfaces: Foreign Body Reaction Issues.Frontiers in neuroscience · 2017Review
- Extracellular matrix-based biomaterial scaffolds and the host response.Biomaterials · 2016Review
- PEG-Immobilized Keratin for Protein Drug Sequestration and pH-Mediated Delivery.Journal of drug delivery · 2016Article
- Technologies for controlled, local delivery of siRNA.Journal of controlled release : official journal of the Controlled Release Society · 2015Review
- Controlled Angiogenesis in Peptide Nanofiber Composite Hydrogels.ACS biomaterials science & engineering · 2015Article
- Sustained localized presentation of RNA interfering molecules from in situ forming hydrogels to guide stem cell osteogenic differentiation.Biomaterials · 2014Article
- Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine.Progress in polymer science · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Fibrous encapsulation of surgically implanted devices is associated with elevated proliferation and activation of fibroblasts in tissues surrounding these implants, frequently causing foreign body complications. Here we test the hypothesis that inhibition of the expression of mammalian target of rapamycin (mTOR) in fibroblasts can mitigate the soft tissue implant foreign body response by suppressing fibrotic responses around implants. In this study, mTOR was knocked down using small interfering RNA (siRNA) conjugated with branched polyethylenimine (bPEI) in fibroblastic lineage cells in serum-based cell culture as shown by both gene and protein analysis. This mTOR knock-down led to an inhibition in fibroblast proliferation by 70% and simultaneous down-regulation in the expression of type I collagen in fibroblasts in vitro. These siRNA/bPEI complexes were released from poly(ethylene glycol) (PEG)-based hydrogel coatings surrounding model polymer implants in a subcutaneous rodent model in vivo. No significant reduction in fibrous capsule thickness and mTOR expression in the foreign body capsules were observed. The siRNA inefficacy in this in vivo implant model was attributed to siRNA dosing limitations in the gel delivery system, and lack of targeting ability of the siRNA complex specifically to fibroblasts. While in vitro data supported mTOR knock-down in fibroblast cultures, in vivo siRNA delivery must be further improved to produce clinically relevant effects on fibrotic encapsulation around implants.
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What OpenQuestion holds
Registered trials
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.