Osteogenic effect of controlled released rhBMP-2 in 3D printed porous hydroxyapatite scaffold

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 141; pp. 491 - 498
• Main Authors: Wang, Hai, Wu, Gui, Zhang, Jing, Zhou, Kui, Yin, Bo, Su, Xinlin, Qiu, Guixing, Yang, Guang, Zhang, Xianglin, Zhou, Gang, Wu, Zhihong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2016
• Subjects: 3D printing; adhesion; Animals; biocompatibility; bone formation; Bone Morphogenetic Protein 2 - chemistry; Bone Morphogenetic Protein 2 - pharmacokinetics; Bone Morphogenetic Protein 2 - pharmacology; Bone Regeneration - drug effects; cell culture; Cell Survival - drug effects; Cells, Cultured; chitosan; Chitosan - chemistry; coatings; collagen; colloids; Controlled release; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - pharmacology; Drug Liberation; Durapatite - chemistry; Humans; hydroxyapatite; Hydroxyapatite (HA); in vitro studies; in vivo studies; Mesenchymal Stromal Cells - drug effects; micro-computed tomography; Microscopy, Electron, Scanning; Microscopy, Fluorescence; Microspheres; Molecular Imprinting; Osteogenesis - drug effects; Osteogenic effect; Porosity; Rabbits; Recombinant Proteins - chemistry; Recombinant Proteins - pharmacokinetics; Recombinant Proteins - pharmacology; rhBMP-2; scanning electron microscopy; staining; Tissue Scaffolds - chemistry; Transforming Growth Factor beta - chemistry; Transforming Growth Factor beta - pharmacokinetics; Transforming Growth Factor beta - pharmacology; rhBMP-2; Hydroxyapatite (HA); Osteogenic effect; 3D printing; Controlled release
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2016.02.007

[Display omitted] •The porous HA/collagen/rhBMP-2 Microspheres delivery system was successfully fabricated.•Release kinetics of rhBMP-2 showed a biphasic profile.•Its osteoinductivity was confirmed in vitro and in vivo. Recently, 3D printing as effective technology has been highlighted in the biomedical field. Previously, a porous hydroxyapatite (HA) scaffold with the biocompatibility and osteoconductivity has been developed by this method. However, its osteoinductivity is limited. The main purpose of this study was to improve it by the introduction of recombinant human bone morphogenetic protein-2 (rhBMP-2). This scaffold was developed by coating rhBMP-2-delivery microspheres with collagen. These synthesized scaffolds were characterized by Scanning Electron Microscopy (SEM), a delivery test in vitro, cell culture, and the experiments in vivo by a Micro-computed tomography (μCT) scan and histological evaluation of VanGieson staining. SEM results indicated the surface of scaffolds were more fit for the adhesion of hMSCs to coat collagen/rhBMP-2 microspheres. Biphasic release of rhBMP-2 could continue for more than 21 days, and keep its osteoinductivity to induce osteogenic differentiation of hMSCs in vitro. In addition, the experiments in vivo showed that the scaffold had a good bone regeneration capacity. These findings demonstrate that the HA/Collagen/Chitosan Microspheres system can simultaneously achieve localized long-term controlled release of rhBMP-2 and bone regeneration, which provides a promising route for improving the treatment of bone defects.