NDLI: Effect of different sintering methods on bioactivity and release of proteins from PLGA microspheres

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Dormer, Nathan H. Gupta, Vineet Scurto, Aaron M. Berkland, Cory J. Detamore, Michael S.
Description	Country affiliation: United States Author Affiliation: Dormer NH ( Orbis Biosciences, 2002 W. 39th Ave., Kansas City, KS 66103, USA.)
Abstract	Macromolecule release from poly(d,l-lactide-co-glycolide) (PLGA) microspheres has been well-characterized, and is a popular approach for delivering bioactive signals from tissue-engineered scaffolds. However, the effect of some processing solvents, sterilization, and mineral incorporation (when used in concert) on long-term release and bioactivity has seldom been addressed. Understanding these effects is of significant importance for microsphere-based scaffolds, given that these scaffolds are becoming increasingly more popular, yet growth factor activity following sintering and/or sterilization is heretofore unknown. The current study evaluated the 6-week release of transforming growth factor (TGF)-ß3 and bone morphogenetic protein (BMP)-2 from PLGA and PLGA/hydroxyapatite (HAp) microspheres following exposure to ethanol (EtOH), dense phase carbon dioxide (CO2), or ethylene oxide (EtO). EtO was chosen based on its common use in scaffold sterilization, whereas EtOH and CO2 were chosen given their importance in sintering microspheres together to create scaffolds. Release supernatants were then used in an accelerated cell stimulation study with human bone marrow stromal cells (hBMSCs) with monitoring of gene expression for major chondrogenic and osteogenic markers. Results indicated that in microspheres without HAp, EtOH exposure led to the greatest amount of delivery, while those treated with CO2 delivered the least growth factor. In contrast, formulations with HAp released almost half as much protein, regardless of EtOH or CO2 exposure. Notably, EtO exposure was not found to significantly affect the amount of protein released. Cell stimulation studies demonstrated that eluted protein samples performed similarly to positive controls in PLGA-only formulations, and ambiguously in PLGA/HAp composites. In conclusion, the use of EtOH, subcritical CO2, and EtO in microsphere-based scaffolds may have only slight adverse effects, and possibly even desirable effects in some cases, on protein availability and bioactivity.
File Format	HTM / HTML
ISSN	09284931
e-ISSN	18730191
DOI	10.1016/j.msec.2013.06.026
Journal	Materials Science and Engineering: C
Issue Number	7
Volume Number	33
Language	English
Publisher	Elsevier
Publisher Date	2013-10-01
Publisher Place	Netherlands
Access Restriction	Open
Subject Keyword	Discipline Materials Science Bone Morphogenetic Protein 2 Pharmacology Lactic Acid Chemistry Microspheres Polyglycolic Acid Tissue Engineering Transforming Growth Factor Beta3 Chondrogenesis Drug Effects Genetics Durapatite Gene Expression Regulation Mesenchymal Stromal Cells Cytology Metabolism Osteogenesis Transition Temperature Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Mechanics of Materials Biomaterials Condensed Matter Physics Bioengineering Mechanical Engineering

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