Controlled release of a heterogeneous human placental matrix from PLGA microparticles to modulate angiogenesis
| Autor: | Peter S. McFetridge, Marc C. Moore, Blanka Sharma, Sarah Tonello, Jon Dobson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Angiogenesis
Cells Placenta Cell Culture Techniques Pharmaceutical Science Neovascularization Physiologic Biocompatible Materials 02 engineering and technology Microparticles 030226 pharmacology & pharmacy Cell-Derived Microparticles Extracellular matrix 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Polylactic Acid-Polyglycolic Acid Copolymer Pregnancy Human Umbilical Vein Endothelial Cells Humans Lactic Acid Microparticle Particle Size Physiologic Cells Cultured Neovascularization Pathologic Female Neovascularization Pathologic Polyglycolic Acid Tissue Scaffolds Cultured Chemistry 021001 nanoscience & nanotechnology Controlled release Lactic acid PLGA Cell culture Immunology Biophysics 0210 nano-technology |
| Popis: | A significant hurdle limiting musculoskeletal tissue regeneration is the inability to develop effective vascular networks to support cellular development within engineered constructs. Due to the inherent complexity of angiogenesis, where multiple biochemical pathways induce and control vessel formation, our laboratory has taken an alternate approach using a matrix material containing angiogenic and osteogenic proteins derived from human placental tissues. Single bolus administrations of the human placental matrix (hPM) have been shown to initiate angiogenesis but vascular networks deteriorated over time. Controlled/sustained delivery was therefore hypothesized to stabilize and extend network formation. To test this hypothesis, hPM was encapsulated in degradable poly(lactic-co-glycolic acid) (PLGA) microparticles to extend the release period. Microparticle preparation including loading, size, encapsulation efficiency, and release profile was optimized for hPM. The angiogenic cellular response to the hPM/PLGA-loaded microparticles was assessed in 3D alginate hydrogel matrices seeded with primary human endothelial cells. Results show an average microparticle diameter of 91.82 ± 2.92 μm, with an encapsulation efficiency of 75%, and a release profile extending over 30 days. Three-dimensional angiogenic assays with hPM-loaded PLGA microparticles showed initial stimulation of angiogenic tubules after 14 days and further defined network formations after 21 days of culture. Although additional optimization is necessary, these studies confirm the effectiveness of a novel controlled multi-protein release approach to induce and maintain capillary networks within alginate tissue scaffolds. |
| Databáze: | OpenAIRE |
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