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

J Biomed Mater Res A. 2019 Oct;107(10):2174-2182. doi: 10.1002/jbm.a.36727. Epub 2019 Jun 11.


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 overexpression 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.

Keywords: 3D printing; bone; regional gene therapy; scaffold; tissue engineering.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / pathology*
  • Disease Models, Animal
  • Genetic Therapy*
  • Male
  • Printing, Three-Dimensional*
  • Rats, Inbred Lew
  • Tissue Scaffolds / chemistry*
  • Wound Healing*
  • X-Ray Microtomography