Controlled release of BMP-2 from a sintered polymer scaffold enhances bone repair in a mouse calvarial defect model

Abstract

Sustained and controlled delivery of growth factors, such as bone morphogenetic protein 2 (BMP-2), from polymer scaffolds has excellent potential for enhancing bone regeneration. The present study investigated the use of novel sintered polymer scaffolds prepared using temperature-sensitive PLGA/PEG particles. Growth factors can be incorporated into these scaffolds by mixing the reconstituted growth factor with the particles prior to sintering. The ability of the PLGA/PEG scaffolds to deliver BMP-2 in a controlled and sustained manner was assessed and the osteogenic potential of these scaffolds was determined in a mouse calvarial defect model. BMP-2 was released from the scaffolds in vitro over 3 weeks. On average, ca. 70% of the BMP-2 loaded into the scaffolds was released by the end of this time period. The released BMP-2 was shown to be active and to induce osteogenesis when used in a cell culture assay. A substantial increase in new bone volume of 55% was observed in a mouse calvarial defect model for BMP-2-loaded PLGA/PEG scaffolds compared to empty defect controls. An increase in new bone volume of 31% was observed for PLGA/PEG scaffolds without BMP-2, compared to empty defect controls. These results demonstrate the potential of novel PLGA/PEG scaffolds for sustained BMP-2 delivery for bone-regeneration applications.

Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

“…[7][8][9] However, a large dose of BMP-2 is necessary for an effective therapeutic effect because BMP-2 stimulates osteoregeneration only at a high concentration, 10,11 and its half-life is as short as 7 minutes in vivo. 11,12 This large dose results in high costs and adverse effects, including inflammation, swelling, ectopic bone formation, and even carcinogenicity. 13 One feasible method to overcome these drawbacks is the selection of alternative GFs that enhance osteoregeneration at lower doses; another is the development of a GF delivery system that finds the ideal balance between releasing the GF at a minimal concentration and delivering it over a sufficiently long duration.…”

New scaffolds encapsulating TGF-β3/BMP-7 combinations driving strong chondrogenic differentiation

“…All the statistical analyses were carried out with GraphPad Prism Version 5.0 software. The integration of growth factors (GFs) in controlled release systems is a useful and much-explored method to improve their efficacy in vivo [28][29][30][31][32]. However, it is assumed that inducing the repair of complex tissues, such as cartilage, might only be possible through the orchestrated co-delivery of two or more GFs.…”

Mesoporous bioactive glass surface modified poly(lactic-co-glycolic acid) electrospun fibrous scaffold for bone regeneration

“…Moreover, BMP-2 molecules contain hydroxyl groups and amino groups that form hydrogen bonds with the Si-OH groups on the MBGs. The sustained release of BMP-2 from the scaffolds may facilitate the regeneration of [55][56][57] In previous research, the release rate of BMP-2 was tuned via MBG, and the sustained release resulted in the formation of mature bone. 58 Following surface modification, mesoporous structure was successfully introduced into the PLGA-MBG fibrous scaffold.…”