Nano-fibrous scaffold for controlled delivery of recombinant human PDGF-BB.
The localized and temporally controlled delivery of growth factors is key to achieving optimal clinical efficacy. In sophisticated tissue engineering strategies, the biodegradable scaffold is preferred to serve as both a three-dimensional (3-D) substrate and a growth factor delivery vehicle to promote cellular activity and enhance tissue neogenesis. This study presents a novel approach to fabricate tissue engineering scaffolds capable of controlled growth factor delivery whereby growth factor containing microspheres were incorporated into 3-D scaffolds with good mechanical properties, well-interconnected macroporous and nano-fibrous structures. The microspheres were uniformly distributed throughout the nano-fibrous scaffold and their incorporation did not interfere the macro-, micro-, and nanostructures of the scaffold. The release kinetics of platelet-derived growth factor-BB (PDGF-BB) from microspheres and scaffolds was investigated using poly(lactic-co-glycolic acid) (PLGA50) microspheres with different molecular weights (6.5 and 64kDa, respectively) and microsphere-incorporated poly(l-lactic acid) (PLLA) nano-fibrous scaffolds. Incorporation of microspheres into scaffolds significantly reduced the initial burst release. Sustained release from several days to months was achieved through different microspheres in scaffolds. Released PDGF-BB was demonstrated to possess biological activity as evidenced by stimulation of human gingival fibroblast DNA synthesis in vitro. The successful generation of 3-D nano-fibrous scaffold incorporating controlled-release factors indicates significant potential for more complex tissue regeneration.
Wei
Guobao
G
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-2209, USA.
Jin
Qiming
Q
Giannobile
William V
WV
Ma
Peter X
PX
D000077214:Becaplermin; D049109:Cell Proliferation; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D049329:Nanostructures; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D016062:Porosity; D020574:Proto-Oncogene Proteins c-sis; D012995:Solubility; D013499:Surface Properties; D023822:Tissue Engineering / Q000379:methods
D003692:Delayed-Action Preparations; D010982:Platelet-Derived Growth Factor; D011091:Polyesters; D011108:Polymers; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)