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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.


Salma E. El-Habashy

Amal H. El-Kamel

Marwa M. Essawy

Elsayeda Zeinab A. Abdelfattah


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.


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.

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
Peer Reviewed Peer Reviewed
Volume 607
Article Number 121002
Keywords Drug repurposing, Extrusion-based printing, Biomimetic scaffolds, Cone beam computed tomography, Hydrogel explants, Controlled release
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