title: Controlled drug release from a novel injectable biodegradable microsphere/scaffold composite based on poly(propylene fumarate).
abstract: The ideal biomaterial for the repair of bone defects is expected to have good mechanical properties, be fabricated easily into a desired shape, support cell attachment, allow controlled release of bioactive factors to induce bone formation, and biodegrade into nontoxic products to permit natural bone formation and remodeling. The synthetic polymer poly(propylene fumarate) (PPF) holds great promise as such a biomaterial. In previous work we developed poly(DL-lactic-co-glycolic acid) (PLGA) and PPF microspheres for the controlled delivery of bioactive molecules. This study presents an approach to incorporate these microspheres into an injectable, porous PPF scaffold. Model drug Texas red dextran (TRD) was encapsulated into biodegradable PLGA and PPF microspheres at 2 microg/mg microsphere. Five porous composite formulations were fabricated via a gas foaming technique by combining the injectable PPF paste with the PLGA or PPF microspheres at 100 or 250 mg microsphere per composite formulation, or a control aqueous TRD solution (200 microg per composite). All scaffolds had an interconnected pore network with an average porosity of 64.8 +/- 3.6%. The presence of microspheres in the composite scaffolds was confirmed by scanning electron microscopy and confocal microscopy. The composite scaffolds exhibited a sustained release of the model drug for at least 28 days and had minimal burst release during the initial phase of release, as compared to drug release from microspheres alone. The compressive moduli of the scaffolds were between 2.4 and 26.2 MPa after fabrication, and between 14.9 and 62.8 MPa after 28 days in PBS. The scaffolds containing PPF microspheres exhibited a significantly higher initial compressive modulus than those containing PLGA microspheres. Increasing the amount of microspheres in the composites was found to significantly decrease the initial compressive modulus. The novel injectable PPF-based microsphere/scaffold composites developed in this study are promising to serve as vehicles for controlled drug delivery for bone tissue engineering.
authors.affiliation: Tissue Engineering and Polymeric Biomaterials Laboratory, Department of Orthopedic Surgery, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Diederik H R
authors.initials: DH
authors.lastname: Kempen
authors.forename: Lichun
authors.initials: L
authors.lastname: Lu
authors.forename: Choll
authors.initials: C
authors.lastname: Kim
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.forename: Wouter J A
authors.initials: WJ
authors.lastname: Dhert
authors.forename: Bradford L
authors.initials: BL
authors.lastname: Currier
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
mesh_terms: D001843:Bone Cements / Q000737:chemistry / Q000378:metabolism*; D001861:Bone Regeneration; D018786:Bone Substitutes / Q000737:chemistry / Q000378:metabolism; D003692:Delayed-Action Preparations; D003911:Dextrans / Q000378:metabolism; D016503:Drug Delivery Systems; D005650:Fumarates / Q000378:metabolism*; D007267:Injections; D019344:Lactic Acid / Q000378:metabolism*; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000378:metabolism*; D011126:Polypropylenes / Q000378:metabolism*; D013499:Surface Properties; D023822:Tissue Engineering / Q000379:methods; D014966:Xanthenes / Q000378:metabolism
chemical_list: D001843:Bone Cements; D018786:Bone Substitutes; D003692:Delayed-Action Preparations; D003911:Dextrans; D005650:Fumarates; D011108:Polymers; D011126:Polypropylenes; D014966:Xanthenes; C097850:poly(propylene fumarate); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C034657:Texas red