Regional gene therapy with 3D printed scaffolds to heal critical sized bone defects in a rat model

Ram Alluri; Xuan Song; Sofia Bougioukli; William Pannell; Venus Vakhshori; Osamu Sugiyama; Amy Tang; Sang-Hyun Park; Yong Chen; Jay R Lieberman

doi:10.1002/jbm.a.36727

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Regional gene therapy with 3D printed scaffolds to heal critical sized bone defects in a rat model

Journal article

Peer reviewed

Regional gene therapy with 3D printed scaffolds to heal critical sized bone defects in a rat model

Ram Alluri, Xuan Song, Sofia Bougioukli, William Pannell, Venus Vakhshori, Osamu Sugiyama, Amy Tang, Sang-Hyun Park, Yong Chen and Jay R Lieberman

Journal of biomedical materials research. Part A, Vol.107(10), pp.2174-2182

10/2019

DOI: 10.1002/jbm.a.36727

PMID: 31112357

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https://www.ncbi.nlm.nih.gov/pmc/articles/7699135View

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Abstract

The objective of the present study was to assess the ability of transduced rat bone marrow cells (RBMCs) that overexpress BMP-2 loaded on a three-dimensionally (3D) printed scaffold to heal a critical sized rat femoral defect. Tricalcium phosphate (TCP) scaffolds were 3D printed to fit a critical sized rat femoral defect. The RBMCs were transduced with a lentiviral (LV) vector expressing BMP-2 or GFP. The rats were randomized into the following treatment groups: (1) RBMC/LV-BMP-2 + TCP, (2) RBMC/LV-GFP + TCP, (3) nontransduced RBMCs + TCP, (4) TCP scaffold alone. The animals were euthanized at 12 weeks and evaluated with plain radiographs, microcomputed tomography (micro-CT), histology, histomorphometry, and biomechanically. Each LV-BMP-2 + TCP treated specimen demonstrated complete healing of the femoral defect on plain radiographs and micro-CT. No femurs healed in the control groups. Micro-CT demonstrated that LV-BMP-2 + TCP treated femoral defects formed 197% more bone volume compared to control groups ( p < 0.05). Histologic analysis demonstrated bone formation across the TCP scaffold, uniting the femoral defect on both ends in the LV-BMP-2 + TCP treated specimens. Biomechanical assessment demonstrated similar stiffness ( p = 0.863), but lower total energy to failure, peak torque, and peak displacement ( p < 0.001) of the femurs treated with LV-BMP-2 + TCP when compared to the contralateral control femur. Regional gene therapy induced over-expression of BMP-2 via transduced RBMCs combined with an osteoconductive 3D printed TCP scaffold can heal a critically sized femoral defect in an animal model. The combination of regional gene therapy and 3D printed osteoconductive scaffolds has significant clinical potential to enhance bone regeneration.

3D printing

bone

regional gene therapy

scaffold

tissue engineering

Details

Title: Subtitle: Regional gene therapy with 3D printed scaffolds to heal critical sized bone defects in a rat model
Creators: Ram Alluri - University of Southern California
Xuan Song - University of Iowa
Sofia Bougioukli - University of Southern California
William Pannell - University of Southern California
Venus Vakhshori - University of Southern California
Osamu Sugiyama - University of Southern California
Amy Tang - University of Southern California
Sang-Hyun Park - Orthopaedic Research
Yong Chen - University of Southern California
Jay R Lieberman - University of Southern California
Resource Type: Journal article
Publication Details: Journal of biomedical materials research. Part A, Vol.107(10), pp.2174-2182
DOI: 10.1002/jbm.a.36727
PMID: 31112357
NLM abbreviation: J Biomed Mater Res A
ISSN: 1549-3296
eISSN: 1552-4965
Grant note: DOI: 10.13039/100000009, name: Foundation for the National Institutes of Health, award: R01AR057076
Language: English
Date published: 10/2019
Academic Unit: Industrial and Systems Engineering; Injury Prevention Research Center; Mechanical Engineering
Record Identifier: 9984186959402771

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