Comparison of in-situ versus ex-situ delivery of polyethylenimine-BMP-2 polyplexes for rat calvarial defect repair via intraoperative bioprinting

Kazim K. Moncal, Miji Yeo, Nazmiye Celik, Timothy M. Acri, Elias Rizk, Hwabok Wee, Gregory S. Lewis, Aliasger K. Salem, Ibrahim T. Ozbolat

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Article number015011
JournalBiofabrication
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2023

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

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