Three‐dimensional fibrous PLGA/HAp composite scaffold for BMP‐2 delivery

Abstract

A protein loaded three-dimensional scaffold can be used for protein delivery and bone tissue regeneration. The main objective of this project was to develop recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded poly(D,L-lactide-co-glycolide)/hydroxylapatite (PLGA/HAp) composite fibrous scaffolds through a promising fabrication technique, electrospinning. In vitro release of BMP-2 from these scaffolds, and the attachment ability and viability of marrow derived messenchymal stem cells (MSCs) in the presence of the scaffolds were investigated. The PLGA/HAp composite scaffolds developed in this study exhibit good morphology and it was observed that HAp nanoparticles were homogeneously dispersed inside PLGA matrix within the scaffold. The composite scaffolds allowed sustained (2-8 weeks) release of BMP-2 whose release rate was accelerated with increasing HAp content. It was also shown that BMP-2 protein successfully maintained its integrity and natural conformations after undergoing the process of electrospinning. Cell culture experiments showed that the encapsulation of HAp could enhance cell attachment to scaffolds and lower cytotoxicity.

Functionalizing PLGA and PLGA Derivatives for Drug Delivery and Tissue Regeneration Applications

“…[131] For instance, a composite nanofiber composed by PLGA and hydroxyapatite (HAp) was developed by electrospinning, for recombinant human bone morphogenetic protein-2 (rhBMP-2) delivery. [132] Authors demonstrated that rhBMP-2 was successfully loaded into the composite nanofibers, being released in a controlled manner (2-8 weeks) without loss of its integrity. [132] Since bone regeneration treatment is difficult and complex to access, this strategy might orientate researchers for new therapeutic solutions.…”

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

“…Several researchers have utilized this well-characterized copolymer for encapsulation and release of a wide variety of bioactive molecules and drugs including TGF-b, BMPs, IGFs, VEGF, NGF, DNA, vancomycin, gentamysin, cisplatin, and others. [261][262][263][264][265][266][267][268] To successfully fabricate and encapsulate PLGA scaffold with these molecules, a wide variety of creative approaches have been taken such as emulsion freeze-drying, 269 nano and microparticle encapsulation, [270][271][272] double emulsion solvent extraction, 273 electrospinning, [274][275][276] compression molding, 277 and others. As mentioned earlier, a fundamental problem with utilizing growth factors is their characteristic short half life in physiological environments.…”

Electrospun Nanofibers for Regenerative Medicine

“…One study reported a burst release during the first 5 days, with complete release within 20 days. [36] The release profiles for scaffolds prepared by electrospinning with a co-axial spinneret or from a solution mixed with bioactive molecules are similar to each other: there is an initial burst release followed by a sustained, first order release. [41] The initial burst release can be attributed to the migration of the growth factors during the drying process, which tends to concentrate a certain fraction of the growth factor molecules near the surface of the fibers.…”