Controlled Co-delivery of pPDGF-B and pBMP-2 from intraoperatively bioprinted bone constructs improves the repair of calvarial defects in rats

Intraoperative bioprinting (IOB), which refers to the bioprinting process performed on a live subject in a surgical setting, has made it feasible to directly deliver gene-activated matrices into craniomaxillofacial (CMF) defect sites. In this study, we demonstrated a novel approach to overcome the c...

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Vydáno v:Biomaterials Ročník 281; s. 121333
Hlavní autoři: Moncal, Kazim K., Tigli Aydın, R. Seda, Godzik, Kevin P., Acri, Timothy M., Heo, Dong N., Rizk, Elias, Wee, Hwabok, Lewis, Gregory S., Salem, Aliasger K., Ozbolat, Ibrahim T.
Médium: Journal Article
Jazyk:angličtina
Vydáno: Netherlands Elsevier Ltd 01.02.2022
Témata:
Animals
biocompatible materials
bioprinting
Bioprinting - methods
Bone and Bones
bone formation
Bone Morphogenetic Protein 2 - pharmacology
bone morphogenetic proteins
Bone Regeneration - genetics
bones
Controlled co-delivery
gene transfer
Gene Transfer Techniques
Humans
In-situ delivery
Intraoperative bioprinting
Osteogenesis
Plasmid-DNAs
Rats
Controlled co-delivery
Plasmid-DNAs
In-situ delivery
Intraoperative bioprinting
ISSN:0142-9612, 1878-5905, 1878-5905
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Shrnutí:Intraoperative bioprinting (IOB), which refers to the bioprinting process performed on a live subject in a surgical setting, has made it feasible to directly deliver gene-activated matrices into craniomaxillofacial (CMF) defect sites. In this study, we demonstrated a novel approach to overcome the current limitations of traditionally fabricated non-viral gene delivery systems through direct IOB of bone constructs into defect sites. We used a controlled co-delivery release of growth factors from a gene-activated matrix (an osteogenic bioink loaded with plasmid-DNAs (pDNA)) to promote bone repair. The controlled co-delivery approach was achieved from the combination of platelet-derived growth factor-B encoded plasmid-DNA (pPDGF-B) and chitosan-nanoparticle encapsulating pDNA encoded with bone morphogenetic protein-2 (CS-NPs(pBMP2)), which facilitated a burst release of pPDGF-B in 10 days, and a sustained release of pBMP-2 for 5 weeks in vitro. The controlled co-delivery approach was tested for its potential to repair critical-sized rat calvarial defects. The controlled-released pDNAs from the intraoperatively bioprinted bone constructs resulted in ∼40% bone tissue formation and ∼90% bone coverage area at 6 weeks compared to ∼10% new bone tissue and ∼25% total bone coverage area in empty defects. The delivery of growth factors incorporated within the intraoperatively bioprinted constructs could pose as an effective way to enhance bone regeneration in patients with cranial injuries in the future.
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K.K.M, R.S.T.A., and I.T.O developed the ideas and designed the experimental plan. R.S.T.A developed the CS-NPs and characterized EE (%), release profiles, osteogenic differentiation capabilities and in-vitro bioprinting and IOB. T.M.A. produced pDNAs and performed the stability test. K.K.M. performed material characterizations including SEM, ATR-FTIR, in-vitro bioprinting, IOB, animal studies, cryosectioning contributions with K.P.G and histomorphometric characterizations. D.N.H. performed RT-PCR and IFS. E.R. performed surgeries. H.B.W performed μCT scanning and analyzed the data with G.L. K.K.M and R.S.T.A wrote the manuscript and all the authors approved the content of the manuscript.
Author Contributions
Contributed equally
ISSN:0142-9612
1878-5905
1878-5905
DOI:10.1016/j.biomaterials.2021.121333