Journal
BIOMATERIALS
Volume 281, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121333
Keywords
Intraoperative bioprinting; In-situ delivery; Controlled co-delivery; Plasmid-DNAs
Funding
- International Team for Implantology Award [1275_2017]
- National Institute of Dental and Craniofacial Research Award [R01DE028614]
- National Science Foundation [1600118]
- Osteology Foundation [15-042]
- International Postdoctoral Research Scholarship Program of the Scientific and Technological Research Council of Turkey (TUBITAK) [BIDEP 2219]
- Div Of Civil, Mechanical, & Manufact Inn
- Directorate For Engineering [1600118] Funding Source: National Science Foundation
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In this study, we demonstrated a novel approach to directly deliver gene-activated matrices into craniofacial defect sites through intraoperative bioprinting. The controlled co-delivery of growth factors from the bioprinted constructs resulted in improved bone tissue formation and coverage. This method shows promising potential for enhancing bone regeneration in patients with cranial injuries.
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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