Silk fibroin microparticles as carriers for delivery of human recombinant BMPs. Physical characterization and drug release.

Bone morphogenetic proteins (BMPs) are cytokines with strong ability to promote new bone formation. Herein, we report the use of silk fibroin microparticles as carriers for the delivery of BMP-2, BMP-9 or BMP-14. BMP-containing fibroin microparticles were prepared by a mild methodology using dropwise addition of ethanol, exhibiting mean diameters of 2.7 +/- 0.3 microm. Encapsulation efficiencies varied between 67.9 +/- 6.1 % and 97.7 +/- 2.0 % depending on the type and the amount of BMP loaded. Release kinetics showed that BMP-2, BMP-9 and BMP-14 were released in two phases profile, with a burst release in the first two days followed by a slower release, for a period of 14 days. The release data were best explained by Korsmeyer's model and the Fickian model of drug diffusion. Silk fibroin microparticles can offer a promising approach for the sustained delivery of different BMPs in tissue engineering applications.

Expression, purification and osteogenic bioactivity of recombinant human BMP-4, -9, -10, -11 and -14.

Bone morphogenetic proteins (BMPs) are cytokines from the TGF-beta superfamily, with important roles during embryonic development and in the induction of bone and cartilage tissue differentiation in the adult body. In this contribution, we report the expression of recombinant human BMP-4, BMP-9, BMP-10, BMP-11 (or growth differentiation factor-11, GDF-11) and BMP-14 (GDF-5), using Escherichia coli pET-25b vector. BMPs were overexpressed, purified by affinity his-tag chromatography and shown to induce the expression of early markers of bone differentiation (e.g. smad-1, smad-5, runx2/cbfa1, dlx5, osterix, osteopontin, bone sialoprotein and alkaline phosphatase) in C2C12 cells and in human adipose stem cells. The described approach is a promising method for producing large amounts of different recombinant BMPs that show potential for novel biomedical applications.

Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery).

Bone morphogenetic proteins (BMPs) are cytokines with a strong effect on bone and cartilage growth and with important roles during embryonic patterning and early skeletal formation. BMPs have promising potential for clinical bone and cartilage repair, working as powerful bone-inducing components in diverse tissue-engineering products. Synthetic polymers, natural origin polymers, inorganic materials and composites may be used as carriers for the delivery of BMPs. Carriers range from nanoparticles to complex three-dimensional (3D) scaffolds, membranes for tissue-guided regeneration, biomimetic surfaces and smart thermosensitive hydrogels. Current clinical uses include spinal fusion, healing of long bone defects and craniofacial and periodontal applications, amongst others. BMP-2 and BMP-7 have recently received approval by the US Food and Drug Administration (FDA) for specific clinical cases, delivered in absorbable collagen sponges. Considering the expanding number of publications in the field of BMPs, there are prospects of a brilliant future in the field of regenerative medicine of bone and cartilage with the use of BMPs.

Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts).

Discovered in 1965, bone morphogenetic proteins (BMPs) are a group of cytokines from the transforming growth factor-beta (TGFbeta) superfamily with significant roles in bone and cartilage formation. BMPs are used as powerful osteoinductive components of diverse tissue-engineering products for the healing of bone. Several BMPs with different physiological roles have been identified in humans. The purpose of this review is to cover the biological function of the main members of BMP family, the latest research on BMPs signalling pathways and advances in the production of recombinant BMPs for tissue engineering purposes.