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Polydopamine functionalized VEGF gene-activated 3D printed scaffolds for bone regeneration
Journal article   Open access   Peer reviewed

Polydopamine functionalized VEGF gene-activated 3D printed scaffolds for bone regeneration

Jaidev L Chakka, Timothy Acri, Noah Z Laird, Ling Zhong, Kyungsup Shin, Satheesh Elangovan and Aliasger K Salem
RSC advances, Vol.11(22), pp.13282-13291
04/08/2021
DOI: 10.1039/d1ra01193f
PMCID: PMC8697638
PMID: 35423856
url
https://doi.org/10.1039/d1ra01193fView
Published (Version of record) Open Access

Abstract

Bone is a highly vascularized organ and the formation of new blood vessels is essential to regenerate large critical bone defects. In this study, polylactic acid (PLA) scaffolds of 20-80% infill were three-dimensionally (3D) printed using a fused deposition modeling based 3D printer. The PLA scaffolds were coated with polydopamine (PDA) and then were surface-functionalized with polyethyleneimine (PEI) and VEGF-encoding plasmid DNA (pVEGF) nanoplexes (PLA-PDA-PEI-pVEGF). The PLA-PDA-PEI-pVEGF scaffolds with 40% infill demonstrated higher encapsulation efficiency and sustained release of pVEGF than scaffolds with 20, 60 and 80% infill and were therefore used for in vitro and in vivo studies. The PLA-PDA-PEI-pVEGF increased the translation and secretion of VEGF and BMP-2. The PLA-PDA-PEI-pVEGF also yielded a 2- and 4.5-fold change in VEGF and osteocalcin gene expression in vitro , respectively. A tube formation assay using human umbilical vascular endothelial cells (HUVECs) showed a significant increase in tube length when exposed to the PLA-PDA-PEI-pVEGF scaffold, in comparison to PLA and PLA-PDA scaffolds. The PLA-PDA-PEI-pVEGF scaffold in an in vivo rat calvarial critical bone defect model demonstrated 1.6-fold higher new bone formation compared to the PLA-PDA scaffold. H&E and Masson's trichrome staining of bone sections also revealed that the PLA-PDA-PEI-pVEGF scaffold facilitated the formation of more blood vessels in the newly formed bone compared to the PLA and PLA-PDA scaffold groups. Thus, PLA-PDA-PEI-pVEGF might be a potential 3D printed gene activated scaffold for bone regeneration in clinical situations. Bone is a highly vascularized organ and the formation of new blood vessels is essential to regenerate large critical bone defects.

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