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Investigation of Localized Delivery of Diclofenac Sodium from Poly(D,L-Lactic Acid-co-Glycolic Acid)/Poly(Ethylene Glycol) Scaffolds Using an In Vitro Osteoblast Inflammation Model
- Source :
- Tissue Engineering Part A. 21:362-373
- Publication Year :
- 2015
- Publisher :
- Mary Ann Liebert Inc, 2015.
-
Abstract
- Nonunion fractures and large bone defects are significant targets for osteochondral tissue engineering strategies. A major hurdle in the use of these therapies is the foreign body response of the host. Herein, we report the development of a bone tissue engineering scaffold with the ability to release anti-inflammatory drugs, in the hope of evading this response. Porous, sintered scaffolds composed of poly(D,L-lactic acid-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) were prepared with and without the anti-inflammatory drug diclofenac sodium. Analysis of drug release over time demonstrated a profile suitable for the treatment of acute inflammation with ∼80% of drug released over the first 4 days and a subsequent release of around 0.2% per day. Effect of drug release was monitored using an in vitro osteoblast inflammation model, comprised of mouse primary calvarial osteoblasts stimulated with proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Levels of inflammation were monitored by cell viability and cellular production of nitric oxide (NO) and prostaglandin E2 (PGE2). The osteoblast inflammation model revealed that proinflammatory cytokine addition to the medium reduced cell viability to 33%, but the release of diclofenac sodium from scaffolds inhibited this effect with a final cell viability of ∼70%. However, releasing diclofenac sodium at high concentrations had a toxic effect on the cells. Proinflammatory cytokine addition led to increased NO and PGE2 production; diclofenac-sodium-releasing scaffolds inhibited NO release by ∼64% and PGE2 production by ∼52%, when the scaffold was loaded with the optimal concentration of drug. These observations demonstrate the potential use of PLGA/PEG scaffolds for localized delivery of anti-inflammatory drugs in bone tissue engineering applications.
- Subjects :
- Diclofenac
Cell Survival
Interleukin-1beta
Biomedical Engineering
Bioengineering
Pharmacology
Nitric Oxide
Models, Biological
Biochemistry
Dinoprostone
Polyethylene Glycols
Proinflammatory cytokine
Biomaterials
Interferon-gamma
Mice
chemistry.chemical_compound
Drug Delivery Systems
Tissue engineering
medicine
Animals
Humans
Viability assay
Polyglactin 910
Cells, Cultured
Inflammation
Osteoblasts
Tissue Scaffolds
Tumor Necrosis Factor-alpha
Skull
Osteoblast
Original Articles
Diclofenac Sodium
PLGA
medicine.anatomical_structure
chemistry
Ethylene glycol
Biomedical engineering
medicine.drug
Subjects
Details
- ISSN :
- 1937335X, 19373341, and 19373368
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Tissue Engineering Part A
- Accession number :
- edsair.doi.dedup.....18f703d5959247f2b0979fe3c68682c9