Table 3. Synthetic Bone–Ligament Scaffolds Have Been Manufactured Using Various Techniques and Biomaterialsa.
| Study | Material bone | Material ligament | Scaffold type | Processing method | Mechanical properties (tensile) | Biological aspect |
|---|---|---|---|---|---|---|
| (190) | Brushite cement | Fibrin cement | Bilayered | Casting and anchoring | EM: 5.5 MPA | In vivo study showed that the treatment with ascorbic acid and proline and adding transforming growth factor-β can lead to increase in collagen content which is necessary for ACL reconstruction. |
| UTS: 42 kPa | ||||||
| (202) | PEGDA-hydrogel with HA | PEGDA-hydrogel with HA and RGD | Bilayered | Freeze-drying | EM and YS: In Pascal range | Addition of HA and incorporation of RGD influenced cell attachment and mechanical properties of the interface scaffold. |
| (191) | Random porosity- Silk fibroin | Aligned porosity- Silk fibroin | Bilayered | Salt leaching and freeze-drying | EM: 690–1320 kPa | Bilayered scaffolds supported cell attachment. The pore alignment in each region influenced the cytoskeleton organization and the gene expression of tendon/ligament, enthesis, and cartilage markers. |
| (206) | PLGA with bioactive glass | Polyglactin-mesh/PLGA | Multilayered (3 layers) | Knitting and sintering | Only compressive tests, no tensile tests. | The in vitro results of the triphasic scaffold exhibited the support of the growth, migration, and phenotypic matrix production of osteoblasts and fibroblasts. Also, the interface scaffold exhibited distinct zonal distributions of cells and phase-specific ECM deposition over time. |
| EM (compressive): 110 MPa | ||||||
| (194) | PLGA with bioactive glass | Polyglactin-mesh/PLGA | Multilayered (3 layers) | Knitting and sintering | Only compressive tests, no tensile tests. | The in vivo results exhibited the formation of distinct yet cellular and matrix regions with various heterogeneity and mineral content. |
| EM (compressive): | ||||||
| Week 0: 100 MPa | ||||||
| Week 8: 85–100 MPa | ||||||
| YS (compressive): | ||||||
| Week 0: 10 MPa | ||||||
| Week 8: 4–4.5 MPa | ||||||
| (195) | PLGA with bioactive glass | Transition zone: PLGA with dichloromethane (DCM) | Multilayered (3 layers) | Sintering | The stratified scaffolds were tricultured by osteoblasts, fibroblasts, chondrocytes. The results showed the formation of structurally contiguous and compositionally distinct regions of bone, fibrocartilage and cartilage. | |
| Ligament: Polyglactin-mesh | ||||||
| (213) | PCL | Aligned PLGA-nanofibers | Multilayered (3 layers) | AM and electrospinning | PCL/mixed/PLGA | Biological investigation of the scaffolds fabricated by the integration of AM and electrospinning showed a promising approach for regeneration of tissue interfaces. |
| EM: 44/51/89 MPa | ||||||
| UTS: 1.6/2.6/5.2 MPa | ||||||
| Ultimate strain: 5%/7%/22% elongation | ||||||
| (203) | Silk fibroin-Chondroitin Sulfate-HAc with HA | Silk fibroin | Multilayered (3 layers) | Knitting and freeze-drying | Pull-out force: 43 N | The scaffold designs showed an enhanced cell proliferation as well as differentiation when respectively seeded with BMSC, chondrocytes and osteoblasts. |
| (208) | Alginate-fibrinogen hydrogel with MSC | Alginate-fibrinogen hydrogel with MSC | Multilayered (3 layers) | Cell-culturing | The in vivo implantation results of primed ligament-cartilage-calcified cartilage constructs represented a promising approach for the regeneration of tissue interfaces. | |
| (204) | PCL with HA | PUR | Gradient | Co-electrospinning | EM: 0.23–2.4 MPa | Cell studies using an MC3T3-E1 osteoprogenitor verified the biocompatibility of the graded meshes. |
| UTS: 0.4–0.62 MPa | ||||||
| (205) | PCL with HA | PUR | Gradient | Co-electrospinning | The biological studies showed that tuning the mineral content can guide the formation of phenotypic gradient which may promote the regeneration of bone–ligament interface. | |
| (60) | PCL with cartilage ECM | PCL with ligament ECM | Gradient | Electrospinning and freeze-drying | The microfiber scaffold functionalized with tissue specific (e.g., ligament) ECM guided the differentiation of MSCs toward the bone–ligament phenotypes. | |
| (198) | PCL-nanofibers with CaP | PCL-nanofibers | Gradient | Electrospinning (2-spinnerets) | Gradient in the content of CaP in nanofiber scaffolds induced a graded response in the adhesion and proliferation of osteogenic cells. | |
| (212) | Random PLGA-nanofibers | Aligned PCL-nanofibers | Gradient | Electrospinning (multiple spinnerets) | Random | Different fiber orientations in multiple regions resulted in region-dependent cell responses. |
| EM: 24–28 MPa | ||||||
| UTS: 24–25 MPa | ||||||
| Aligned | ||||||
| EM: 6.8–9.9 MPa | ||||||
| UTS: 41–50 MPa | ||||||
| (192) | Modified tendon ECM into random organization | Modified tendon ECM into aligned organization | Gradient | Decellularization | The biomimetic tendon ECM (or Random-Aligned-Random) composite scaffold showed enhanced interface properties between bone and fibrocartilage formation in the rabbit ACL reconstruction model in vivo. |
a
The acronyms summarized in this table are EM = elastic modulus, UTS = ultimate tensile strength, YS = yield strength, PEGDA = poly(ethylene glycol)diacrylate, HA = hydroxyapatite, RGD = cell adhesion peptide (Arg-Gly-Asp), PLGA = poly(lactide-co-glycolide) acid, DCM = dichloromethane, PCL = polycaprolactone, ECM = extracellular matrix, HAc = hyaluronic acid, MSC = mesenchymal stem cells, PUR = polyurethane, RGD = red adhesion peptide, BMSC = bone marrow mesenchymal stem cells.