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Comparison of In-Situ versus Ex-Situ Delivery of Polyethylenimine-BMP-2 polyplexes for Rat Calvarial Defect Repair via Intraoperative Bioprinting
Journal article   Peer reviewed

Comparison of In-Situ versus Ex-Situ Delivery of Polyethylenimine-BMP-2 polyplexes for Rat Calvarial Defect Repair via Intraoperative Bioprinting

Kazim Kerim Moncal, Miji Yeo, Nazmiye T Celik, Timothy Acri, Elias V Rizk, Hwabok Wee, Gregory S Lewis, Aliasger K Salem and Ibrahim T Ozbolat
Biofabrication, Vol.15(1), 015011
01/2023
DOI: 10.1088/1758-5090/ac9f70
PMCID: PMC10012389
PMID: 36322966
url
https://pmc.ncbi.nlm.nih.gov/articles/PMC10012389/pdf/nihms-1871058.pdfView
Open Access

Abstract

Gene therapeutic applications combined with bio- and nano-materials have been used to address current shortcomings in bone tissue engineering due to their feasibility, safety and potential capability for clinical translation. Delivery of non-viral vectors can be altered using gene-activated matrices to improve their efficacy to repair bone defects. Ex-situ and in-situ delivery strategies are the most used methods for bone therapy, which have never been directly compared for their potency to repair critical-sized bone defects. In this regard, we first time explore the delivery of polyethylenimine (PEI) complexed plasmid DNA encoding bone morphogenetic protein-2 (PEI-pBMP-2) using the two delivery strategies, ex-situ and in-situ delivery. To realize these gene delivery strategies, we employed intraoperative bioprinting (IOB), enabling us to 3D bioprint bone tissue constructs directly into defect sites in a surgical setting. Here, we demonstrated IOB of an osteogenic bioink loaded with PEI-pBMP-2 for the in-situ delivery approach, and PEI-pBMP-2 transfected rat bone marrow mesenchymal stem cells laden bioink for the ex-situ delivery approach as alternative delivery strategies. We found that in-situ delivery of PEI-pBMP-2 significantly improved bone tissue formation compared to ex-situ delivery. Despite debates amongst individual advantages and disadvantages of ex-situ and in-situ delivery strategies, our results ruled in favor of the in-situ delivery strategy, which could be desirable to use for future clinical applications.

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