Polydopamine functionalized VEGF gene-activated 3D printed scaffolds for bone regeneration
Jaidev L Chakka1, Timothy Acri1, Noah Z Laird1
1Department of Pharmaceutics and Experimental Therapeutics, College of Pharmacy, University of Iowa Iowa City IA-52242 USA aliasger-salem@uiowa.edu +1-319-335-8810.
RSC Advances
|April 15, 2022
Summary
3D printed scaffolds enhanced with plasmid DNA (pVEGF) promote new blood vessel and bone formation. This novel scaffold shows promise for regenerating critical bone defects in future clinical applications.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Regenerative Medicine
Background:
- Bone regeneration requires new blood vessel formation.
- Critical-sized bone defects pose significant clinical challenges.
- 3D printing offers customizable scaffolds for tissue engineering.
Purpose of the Study:
- To develop and evaluate a 3D printed polylactic acid (PLA) scaffold functionalized with vascular endothelial growth factor (VEGF)-encoding plasmid DNA (pVEGF) for enhanced bone regeneration.
- To investigate the effect of scaffold infill density on pVEGF encapsulation and release.
- To assess the in vitro and in vivo performance of the functionalized scaffold in promoting vascularization and bone formation.
Main Methods:
- 3D printing of PLA scaffolds with varying infill densities (20-80%).
- Surface functionalization of scaffolds with polydopamine (PDA), polyethyleneimine (PEI), and pVEGF nanoplexes (PLA-PDA-PEI-pVEGF).
- In vitro evaluation of VEGF and BMP-2 expression, gene expression (VEGF, osteocalcin), and endothelial cell tube formation. In vivo assessment in a rat calvarial critical bone defect model, including new bone formation and vascularization analysis.
Main Results:
- PLA-PDA-PEI-pVEGF scaffolds with 40% infill showed optimal pVEGF encapsulation and sustained release.
- Scaffolds significantly increased VEGF and BMP-2 translation and secretion, and upregulated VEGF and osteocalcin gene expression in vitro.
- Enhanced endothelial cell tube formation in vitro and 1.6-fold higher new bone formation in vivo compared to controls.
- Histological analysis confirmed increased vascularization within newly formed bone.
Conclusions:
- The 3D printed PLA-PDA-PEI-pVEGF scaffold effectively promotes vascularization and bone regeneration.
- This gene-activated scaffold demonstrates significant potential for treating critical bone defects.
- Further investigation is warranted for clinical translation of this advanced biomaterial.
