Table 3.
The application of gene therapy for tendon/ligament-to-bone repair in vivo.
| Animal model | Cell | Vehicle | Major results | Ref. | |
|---|---|---|---|---|---|
| TGF-β | Rabbit ACL reconstruction | BMSCs | Injection | The over-expression group exhibited tighter tendon-bone interface, increased number of chondrocyte-like cells and fibrochondrocytes, more collagen fibers, better biomechanical properties and greater bone formation than the inhibition, empty vector and untreated groups. | [131] |
| TGF-β3, BMP-2 | Rabbit ACL reconstruction | BMSCs | Genes-immobilized triphasic silk scaffold | The gene-modified silk scaffold seeded with BMSCs induced approximately complete osseointegration as a result of multilayered tissue formation and robust mechanics as early as 12 weeks. | [132] |
| BMP-2 | Rat supraspinatus tendon repair | ASCs | Aligned nanofibrous PLGA scaffold | The transduced cell group showed evident bone loss at 28 days, decreased strength and modulus at 28 and 56 days. | [64] |
| Rat ACL reconstruction | ACL-derived CD34+ cells | Cell sheet | The cells transduced with BMP-2 had the smallest cross-sectional areas of bone tunnels. Tensile strength was highest in the cells transduced with BMP-2 (100%) group at 4 weeks, and in cells transduced with BMP-2 (25%) group at 8 weeks. Graft-bone integration occurred most rapidly in the cells transduced with BMP-2 (25%) group. | [133] | |
| Rabbit ACL reconstruction | BMSCs | Gastrocnemius tendons wrapped by BMSCs | The infected BMSCs with BMP-2 virus or control virus groups exhibited better biomechanical properties, and an increased perpendicular collagen fibers formation. The cartilage-like cells proliferation and the fibrocartilage-like tissue formation were highest in the infected BMSCs with BMP-2 virus group. | [134] | |
| Rabbit ACL reconstruction | Normal rat kidney cells | Fibrin scaffold | The transfected cell group showed no significant difference of bone mineral density, better contact between tendon and bone, higher failure load and maximal graft tension, more bone tissue and less fibrous tissue, enhanced new vessel formation, cell activity, and remodeling compared with the control group. | [135] | |
| BMP-12 | Rabbit supraspinatus tendon repair | BMSCs | PLGA scaffold | The BMP-12-overexpressing promoted the tendon-to-bone healing, improved collagen fiber organization and fibrocartilage formation at the interface. | [136] |
| BMP-13 | Rat supraspinatus tendon repair | BMSCs | Fibrin glue | The transduced cell group showed no differences in the amount of new cartilage formation, collagen fiber organization, and biomechanical strength compared with untransduced cell group. | [137] |
| FGF-2 | Rabbit extra-articular model | Human amniotic mesenchymal stem cells | Human acellular amniotic membrane | The scaffold loaded with transfected cell group had the narrowest bone tunnel, higher macroscopic and histological scores, the best mechanical strength. | [138] |
TGF-β, transforming growth factor-β; TGF-β3, transforming growth factor-β3; BMP-2/12/13, bone morphogenetic protein-2/12/13; FGF-2, fibroblasts growth factor-2; ACL, anterior cruciate ligament; BMSCs, bone marrow-derived stem cells; PLGA, poly(lactic-co-glycolic acid).