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.

Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities

“…Sodium bicarbonate is the most widely used gas foaming agent given that it generates CO 2 in acidic conditions. [21] However, other carbonates such as potassium carbonate and ammonium bicarbonate [51,52] as well as nitrites such as sodium nitrite [53] have also been reported. The ultimate choice of foaming agent decided based on cost and the safety of both the gas by-products produced as well as the residual products left behind within the formed gel, with the latter considerations particularly important to consider for biomedical applications.…”

Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

“…PPF biomaterials have been shown to support osteoblast attachment and proliferation in vitro, and ingrowth of new bone tissue in vivo (16)(17)(18)(19). Growth factors have been incorporated via PLGA micro-spheres into poly(propylene fumarate) materials for controlled release (20). Two-component biodegradable polyurethane (PUR) networks have also been investigated as scaffolds for tissue engineering.…”

Retraction

“…BMP-2 and IGF-1 have been used in promoting bone formation and, in combination with various delivery carriers, in bone regeneration or bone tissue-engineering practice Puleo, 2004a, 2004b;Kempen, et al, 2006;Chen, et al, 2006b). We reported here the in vitro proliferation and osteogenic differentiation of PDL cells in a novel microsphere/scaffold composite, which could provide dual GFs release in one single device (Chen, et al, 2007a).…”

“…Although this is not the first time attempt to develop biomaterials for both drug delivery and tissue engineering applications (Kempen, et al, 2006;Park, et al, 2006), on-going progress in cell-based therapeutics, progenitor cell exploitation, GF delivery and advanced formulation strategies will always provide a more general and versatile basis for advanced combination device strategies. These seek to improve tissue-device integration and functional tissue regeneration.…”