3D printed bioinspired scaffolds integrating doxycycline nanoparticles: Customizable implants for in vivo osteoregeneration

El-Habashy, Salma E.; El-Kamel, Amal H.; Essawy, Marwa M.; Abdelfattah, Elsayeda Zeinab A.; Eltaher, Hoda M.

Abstract

3D printing has revolutionized pharmaceutical research, with applications encompassing tissue regeneration and drug delivery. Adopting 3D printing for pharmaceutical drug delivery personalization via nanoparticle-reinforced hydrogel scaffolds promises great regenerative potential. Herein, we engineered novel core/shell, bio-inspired, drug-loaded polymeric hydrogel scaffolds for pharmaceutically personalized drug delivery and superior osteoregeneration. Scaffolds were developed using biopolymeric blends of gelatin, polyvinyl alcohol and hyaluronic acid and integrated with composite doxycycline/hydroxyapatite/polycaprolactone nanoparticles (DX/HAp/PCL) innovatively via 3D printing. The developed scaffolds were optimized for swelling pattern and in-vitro drug release through tailoring the biphasic microstructure and wet/dry state to attain various pharmaceutical personalization platforms. Freeze-dried scaffolds with nanoparticles reinforcing the core phase (DX/HAp/PCL-LCS-FD) demonstrated favorably controlled swelling, preserved structural integrity and controlled drug release over 28 days. DX/HAp/PCL-LCS-FD featured double-ranged pore size (90.4 ± 3.9 and 196.6 ± 38.8 µm for shell and core phases, respectively), interconnected porosity and superior mechanical stiffness (74.5 ± 6.8 kPa) for osteogenic functionality. Cell spreading analysis, computed tomography and histomorphometry in a rabbit tibial model confirmed osteoconduction, bioresorption, immune tolerance and bone regenerative potential of the original scaffolds, affording complete defect healing with bone tissue. Our findings suggest that the developed platforms promise prominent local drug delivery and bone regeneration.

Citation

El-Habashy, S. E., El-Kamel, A. H., Essawy, M. M., Abdelfattah, E. Z. A., & Eltaher, H. M. (2021). 3D printed bioinspired scaffolds integrating doxycycline nanoparticles: Customizable implants for in vivo osteoregeneration. International Journal of Pharmaceutics, 607, Article 121002. https://doi.org/10.1016/j.ijpharm.2021.121002

• Journal Article Type: Article
• Acceptance Date: Aug 9, 2021
• Online Publication Date: Aug 12, 2021
• Publication Date: Sep 25, 2021
• Deposit Date: Apr 26, 2023
• Journal: International Journal of Pharmaceutics
• Print ISSN: 0378-5173
• Electronic ISSN: 1873-3476
• Publisher: Elsevier BV
• Peer Reviewed: Peer Reviewed
• Volume: 607
• Article Number: 121002
• DOI: https://doi.org/10.1016/j.ijpharm.2021.121002
• Keywords: Drug repurposing, Extrusion-based printing, Biomimetic scaffolds, Cone beam computed tomography, Hydrogel explants, Controlled release
• Public URL: https://nottingham-repository.worktribe.com/output/8771421
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0378517321008085?via%3Dihub