title: Controlled release of a heterogeneous human placental matrix from PLGA microparticles to modulate angiogenesis.
abstract: 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.
authors: J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, JG-56 Biomedical Sciences Building, P.O. Box 116131, Gainesville, FL, 32611-6131, USA.
authors: Sarah
authors: S
authors: Tonello
authors: J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, JG-56 Biomedical Sciences Building, P.O. Box 116131, Gainesville, FL, 32611-6131, USA.
authors: Marc C
authors: MC
authors: Moore
authors: J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, JG-56 Biomedical Sciences Building, P.O. Box 116131, Gainesville, FL, 32611-6131, USA.
authors: Blanka
authors: B
authors: Sharma
authors: J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, JG-56 Biomedical Sciences Building, P.O. Box 116131, Gainesville, FL, 32611-6131, USA.|Department of Materials Science and Engineering, University of Florida, Gainesville, FL, 32611, USA.
authors: Jon
authors: J
authors: Dobson
authors: J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, JG-56 Biomedical Sciences Building, P.O. Box 116131, Gainesville, FL, 32611-6131, USA. pmcfetridge@bme.ufl.edu.
authors: Peter S
authors: PS
authors: McFetridge
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D018929:Cell Culture Techniques; D055252:Cell-Derived Microparticles / Q000737:chemistry / Q000648:ultrastructure*; D002478:Cells, Cultured; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010316:Particle Size; D010920:Placenta / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011247:Pregnancy; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Angiogenesis; Extracellular matrix; Microparticles