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

Abstract

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 µm. 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.

A New Preparation Method for Anisotropic Silk Fibroin Nerve Guidance Conduits and Its Evaluation In Vitro and in a Rat Sciatic Nerve Defect Model

“…The mixture of CaCl 2 /H 2 O/ethanol dissolves native silk fibers, 32,33 while methanol induces the formation of b-sheets, leading to a crystalline-like structure of the SF. 34,35 FA functions as a solving and crystallizing agent.…”

Biodegradable Polymers for Focal Delivery Systems

“…Silk fi broin microparticles offer a promising approach for the sustained delivery of different bone morphogenetic proteins (BMPs) in tissue-engineering applications. BMPs like BMP-2, BMP-9, or BMP-14 are cytokines with the strong ability to promote new bone formations [ 32 ]. Silk fi broin-coated liposomes are used in long-term and targeted drug delivery of many oncolytic agents.…”

Biological approaches toward dental pulp regeneration by tissue engineering

“…However, their release from a scaffold during the regeneration process is still likely to be variable and rather uncontrolled; hence, this will contribute to the unpredictability of their overall effects. The potential of particulate delivery systems for growth factors was promptly perceived as a means to protect biomolecules during tissue regrowth and to offer adequate control over the release rate (Chen et al, 2006a(Chen et al, , 2006bBessa et al, 2010). Tissue regeneration based on protein-loaded particulates that were further integrated into different scaffold types has grown impressively in recent years and led to significant advances in the tissueengineering field (Chen et al, 2007a(Chen et al, , 2007bBessa et al, 2008).…”

“…Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents and desirable physical characteristics, have been the material of choice for applications in pulp regeneration Prescott et al, 2008;Ishimatsu et al, 2009;Kim et al, 2010a). Novel natural hydrogel scaffolds fabricated from both dextranand gelatin-based biomaterials have the capability to release their cargo in a sustained and controlled manner and eventually may provide time-and space-dependent therapeutic protein levels during all stages of tissue regrowth (Srinivasan et al, 1999;Smith, 2003;Silva et al, 2004;Zhang et al, 2005b;Chen et al, 2006aChen et al, , 2006bGoldberg et al, 2006;Vasita and Katti, 2006;Chen et al, 2007aChen et al, , 2007bChen et al, , 2009aBessa et al, 2008;Yilgor et al, 2009;Bessa et al, 2010). Although one can imagine multiple opportunities to formulate new biomaterials with bioactive ingredients, or even to use existing biomaterials with subtle modifications, the extant knowledge is far too limited to propose an efficient and logical pathway to achieve the aim of dentine-pulp complex regeneration (Ferracane et al, 2010).…”