3D printed hyperelastic “bone” scaffolds and regional gene therapy: A novel approach to bone healing

Abstract

The purpose of this study was to evaluate the viability of human adipose-derived stem cells (ADSCs) transduced with a lentiviral (LV) vector to overexpress bone morphogenetic protein-2 (BMP-2) loaded onto a novel 3D printed scaffold. Human ADSCs were transduced with a LV vector carrying the cDNA for BMP-2. The transduced cells were loaded onto a 3D printed Hyperelastic "Bone" (HB) scaffold. In vitro BMP-2 production was assessed using enzyme-linked immunosorbent assay analysis. The ability of ADSCs loaded on the HB scaffold to induce in vivo bone formation in a hind limb muscle pouch model was assessed in the following groups: ADSCs transduced with LV-BMP-2, LV-green fluorescent protein, ADSCs alone, and empty HB scaffolds. Bone formation was assessed using radiographs, histology and histomorphometry. Transduced ADSCs BMP-2 production on the HB scaffold at 24 hours was similar on 3D printed HB scaffolds versus control wells with transduced cells alone, and continued to increase after 1 and 2 weeks of culture. Bone formation was noted in LV-BMP-2 animals on plain radiographs at 2 and 4 weeks after implantation; no bone formation was noted in the other groups. Histology demonstrated that the LV-BMP-2 group was the only group that formed woven bone and the mean bone area/tissue area was significantly greater when compared with the other groups. 3D printed HB scaffolds are effective carriers for transduced ADSCs to promote bone repair. The combination of gene therapy and tissue engineered scaffolds is a promising multidisciplinary approach to bone repair with significant clinical potential. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1104-1110, 2018.

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

“…Prior studies have evaluated 3D printed scaffolds loaded with osteoinductive stimulants such as nontransduced stem cells or rhBMP‐2 (Roskies et al, ; Temple et al, ). Only one study has evaluated the combination of regional gene therapy and a 3D printed scaffold; it demonstrated proof of concept that ectopic bone could be formed in a mouse muscle pouch; however, this study did not investigate the ability of the tissue engineering strategy to heal a stringent bone defect model (Alluri et al, ).…”

Synergistic Effects of Controlled-Released BMP-2 and VEGF from nHAC/PLGAs Scaffold on Osteogenesis

“…As the parent phase of the scaffold, collagen interweaves into a three-dimensional porous network structure [ 20 ], which is beneficial to the attachment of nHA and PLGA microspheres and seed cells. However, poor bending strength and overquick degradation rate of collagen confine its further application [ 21 , 22 ]. Addition of nHA provided ergonomic strength and potent osteoconduction and osteoinduction [ 23 – 25 ].…”

Hierarchical cellular scaffolds fabricated via direct foam writing using gelled colloidal particle‐stabilized foams as the ink

“…4,5 Until now, multiple additive manufacturing approaches have been developed to create hierarchical cellular structures. Among these methods, direct ink writing (DIW) is an attractive and versatile 3D printing technology to construct multifunctional structures for the applications in various fields ranging from smart composites, 6,7 bioinspired materials, 8,9 and electron component. 10,11 During such printing process, viscoelastic inks are squeezed out of the nozzles to form filamentary struts and finally become various patterns according to the prescribed motion of nozzles.…”