TABLE 1.
Summary of nanofiber-based tendon regeneration scaffolds.
| References | Application | Animal model | Scaffold | Material | Cell | Bioactive molecule | Morphology | Mechanical properties | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fiber diameter | Porosity (%) | Young’s modulus (MPa) | Ultimate stress (MPa) | Yield stress (MPa) | Ultimate stress (%) | Stiffness (N/mm) | Maximum force (N) | ||||||||
| Yang et al. (2019) | Achilles tendon | In vivo rat | Aligned and Random | Insoluble collagen | rBMSCs | — | 2–4 μm | As-fabricated | Radial tensile: 31.12 ± 1.19 (CMA) 43.28 ± 2.49 (CMR) axial tensile: 79.19 ± 9.39 (CMA) 74.91 ± 1.23 (CMR) 138.33 ± 15.84 (normal) 41.56 ± 9.51 (repair) 34.52 ± 8.19 (CMA) 10.51 ± 1.42 (CMR) 8.14 ± 1.74 (defect) | Radial tensile: 8.97 ± 0.78 (CMA) 11.97 ± 0.58 (CMR) radial tensile: 18.45 ± 0.91 (CMA) 13.81 ± 0.39 (CMR) | Radial tensile: 45.68 ± 5.80 (CMA) 36.37 ± 3.29 (CMR) radial tensile: 28.33 ± 0.81 (CMA) 25.85 ± 2.36 (CMR) 23.26 ± 2.63 (normal) 24.80 ± 2.19 (repair) 31.71 ± 4.43 (CMA) 34.69 ± 0.86 (CMR) 47.19 ± 2.13 (defect) | ||||
| Transplant after 8 weeks | 22.45 ± 1.80 (normal) 5.32 ± 1.05 (repair) 5.02 ± 0.18 (CMA) 1.92 ± 0.17 (CMR) 2.23 ± 0.20 (defect) | 37.90 ± 3.26 (normal) 25.09 ± 4.55 (repair) 24.57 ± 3.95 (CMA) 12.05 ± 2.60 (CMR) 9.64 ± 0.64 (defect) | 70.78 ± 9.01 (normal) 45.02 ± 2.50 (repair) 43.69 ± 7.51 (CMA) 26.46 ± 4.62 (CMR) 32.38 ± 7.72 (defect) | ||||||||||||
| Fernandez ‐ Yague et al. (2021) | Achilles tendon | In vivo rat | Aligned | PVDF-TrFE | — | — | 690 ± 110 nm (non-piezoelectric with drawing) 540 ± 120 nm (piezoelectric w/o drawing) 513 ± 80 nm (piezoelectric with drawing) | — | As-fabricated | 14.5 ± 1.7 (non-piezoelectric with drawing) 56.6 ± 7.6 (piezoelectric w/o drawing) 61.8 ± 8.1 (piezoelectric with drawing) | 16 ± 0.3 (non-piezoelectric with drawing) 15 ± 3.7 (piezoelectric w/o drawing) 31 ± 4.2 (piezoelectric with drawing) | — | 91.3 ± 10.4 (non-piezoelectric with drawing) 46.4 ± 6.1 (piezoelectric w/o drawing) 39.4 ± 3.2 (piezoelectric with drawing) | — | — |
| Yin et al. (2015a) | Achilles tendon | In vivo rat | Aligned and Random | PLLA | rBMSCs | — | 1068 ± 190 nm (aligned) 739 ± 129 nm (random) | — | Transplant after 8 weeks | 24.42 ± 2.20 (aligned) 20.86 ± 3.56 (random) | — | ∼6.5 (aligned) ∼6 (random) | — | ∼32 (aligned) ∼29 (random) | 87.12 ± 5.61 (aligned) 77.09 ± 13.27 (random) |
| Wang et al. (2016) | Achilles tendon | In vivo rat | Aligned and random | PCL/PEO/gelatin | hDFs | — | 1074 ± 158 nm (aligned) 416 ± 114 nm (random) | — | As-fabricated Scaffolds of seeded Cell After 12 weeks transplant subcutaneously 12 weeks transplant after 12 weeks | 0.53 ± 0.059 (aligned) 0.42 ± 0.065 (random) 3.07 ± 0.67 (aligned) 0.76 ± 0.17 (random) 1.74 ± 0.45 (aligned) 0.59 ± 0.17 (random) ∼6 (control) ∼16 (aligned) ∼15 (random) | 134.91 ± 15.94 (aligned) 83.32 ± 11.15 (random) 154.39 ± 24.44 (aligned) 81.80 ± 16.07 (random) 78.74 ± 6.59 (aligned) 51.77 ± 14.51 (random) 261.54 ± 23.48 (control) 206.41 ± 52.59 (aligned) 200.76 ± 49.14 (random) | — | — | — | 9.53 ± 1.13 (aligned) 5.89 ± 0.79 (random) 10.91 ± 1.73 (aligned) 5.78 ± 1.14 (random) 5.56 ± 0.47 (aligned) 3.66 ± 1.02 (random) ∼10 (control) ∼25 (aligned) ∼25 (random) |
| Yao et al. (2022) | Achilles tendon | In vivo rat | Patch-shaped nanofibrous scaffolds | PCL/ALG | rTPSCs | MLT | ∼200 nm nanofibrous | — | As-fabricated | 1.50 ± 0.17 (PCL/MLT electrospun membrane) 0.38 ± 0.03 (PCL/MLT-ALG scaffolds) | — | — | — | — | — |
| Chen et al. (2017) | Achilles tendon | In vivo rabbit | Aligned and Random | PCL/SF | rDFBs | — | 549.4 ± 172.4 nm (RP) 582.5 ± 178.6 nm (RPSF) 363.7 ± 116.0 nm (APSF) | — | As-fabricated transplant after 12 weeks | 15.28 ± 5.31 (RP) 3.93 ± 0.05 (RPSF) 70.52 ± 2.83 (APSF) | 1.48 ± 0.21 (RP) 0.06 ± 0.01 (RPSF) 0.94 ± 0.11 (APSF) | 39.75 ± 6.61 (RP) 2.05 ± 0.30 (RPSF) 1.72 ± 0.19 (APSF) | — | 29.9 ± 5.8 (normal) 4.5 ± 0.7 (acellular RPSF) 10.1 ± 1.8 (acellular APSF) 8.5 ± 1.1 (cells/RPSF) 18.0 ± 3.8 (cells/APSF) | 382.3 ± 58.2 (normal) 114.3 ± 11.6 (acellular RPSF) 216.4 ± 33.0 (acellular APSF) 167.3 ± 25.4 (cells/RPSF) 310.9 ± 73.5 (cells/APSF) |
| Wang et al. (2021) | Achilles tendon | In vivo rat | Parallel-aligned | Collagen | rTSPCs | rPOSTN | — | As-fabricated transplant after 12 weeks | 11.15 ± 1.08 (ACF) 85.05 ± 6.03 (normal) 51.71 ± 8.01 (ACF-rP) ∼30 (ACF) ∼10 (defect) | — | 10.60 ± 0.65 ACF ∼23(Normal) ∼12 (ACF-rP) ∼6 (ACF) ∼2 (Defect) | — | — | 33.31 ± 2.06 ACF ∼90 (normal) 59.55 ± 8.09 (ACF-rP) 44.32 ± 4.32 (ACF) 27.22 ± 7.56 (defect) | |
| Chen et al. (2021a) | Achilles tendon | In vivo rat | Aligned and random | SF | hPDLSCs | — | — | — | As-fabricated | ∼70 KPa random ∼60 KPa aligned | — | — | — | — | ∼1.1 random ∼1.0 aligned |
| Zhang et al. (2018c) | Achilles tendon | In vivo rat | Aligned and random | PLLA | mTSPCs | TSA | 1.63 ± 0.38 μm (A-TSA) 1.73 ± 0.37 μm (A) 1.44 ± 0.23 μm (R-TSA) 1.51 ± 0.23 μm (R) | — | As-fabricated transplant after 4 weeks | 513.09 ± 64.02 (A-TSA) 51.59 ± 11.68 (R-TSA) 51.23 ± 24.95 (A-TSA) 31.00 ± 9.42 (R) | — | 12.50 ± 1.06 (A-TSA) 2.70 ± 0.32 (R-TSA) 6.65 ± 1.38 (A-TSA) 4.20 ± 0.98 (R) | — | 44.50 ± 5.32 (normal) 28.65 ± 10.01 (A-TSA) 19.44 ± 5.38 (R) | 38.27 ± 5.92 (A-TSA) 31.20 ± 5.63 (R) |
| Yuan et al. (2021) | Achilles tendon | In vivo rat | Aligned core-shell | COL1-CS (shell)/PLLA (core) | — | — | 1.60 ± 0.16 μm (PLLA/CS-COL1) 1.91 ± 0.23 μm (PLLA) | — | As-fabricated | 805.63 ± 31.47 (PLLA/CS-COL1) 1973.37 ± 36.85 (PLLA) | — | 30.57 ± 1.94 (PLLA/CS-COL1) 39.83 ± 3.04 (PLLA) | 122.97 ± 4.23% (PLLA/CS-COL1) 72.9 ± 62.95% (PLLA) | — | — |
| Maghdouri-White et al. (2021) | Achilles tendon | In vivo rat/Rabbit/cadaver | Aligned | PDLLA/Collagen I | Human tenocytes/hMSCs | PRP | ∼500 nm | — | As-fabricated scaffolds of seeded Cell After7 days | 152.2 ± 15.85 ∼160 (PRP Coated) ∼30 (Non-coated) | — | 13.6 ± 0.26 ∼25 (PRP Coated) ∼8 (Non-coated) | ∼20 (PRP Coated) ∼30 (Non-coated) | 8.4 ± 1.77 ∼10 (PRP Coated) ∼12 (Non-coated) | |
| Weng et al. (2022) | Achilles tendon | In vivo rat | Aligned | PLGA | — | Simvastatin | 330.6 ± 137.3 nm (1:1) 390.3 ± 134.4 nm (2:1) | — | Transplant after 1 week transplant after 2 weeks transplant after 4 weeks | — | — | — | — | — | 14.96 ± 2.76 (normal) 12.43 ± 2.36 (PLGA/S) 2.59 ± 1.89 (PLGA) 3.06 ± 4.79 (control) 11.01 ± 1.06 (normal) 16.47 ± 8.09 (PLGA/S) 9.48 ± 1.65 (PLGA) 4.95 ± 1.70 (control) 26.14 ± 4.13 (normal) 13.20 ± 3.70 (PLGA/S) 9.22 ± 2.35 (PLGA) 11.82 ± 3.09 (control) |
| Yin et al. (2020) | Achilles tendon | In vitro | Nanofibers | RADA | hTSPCs | RGD | 10 nm | — | — | — | — | — | — | — | — |
| Almeida et al. (2019) | Achilles tendon | In vivo rabbit | Dimensional hybrid | Bovine bollagen molecule | — | — | 272 ± 183 nm (aligned nanofibers) 2.54 ± 0.68 μm (polymerized microfibers) | randomly formed: 36.12% ± 6.59%; highly aligned: 11.01% ± 3.97% | As fabricated | 43.81 ± 4.19 kpa (cross-linked) 4.05 ± 1.28 kpa (non-cross-linked) | — | 2.69 ± 0.47 (cross-linked) 0.40 ± 0.11 (non-cross-linked) | 61.34 ± 4.71 (cross-linked) 98.55 ± 7.23 (non-cross-linked) | — | 28.33 ± 2.19 (cross-linked) 4.56 ± 1.92 (non-cross-linked) |
| Moshiri et al. (2013) | Achilles tendon | In vivo rabbit | Sheath and core | Collagen/PDS | — | — | — | 17.62% ± 4.88% | As fabricated: transplant after 60 days after 120 days | 4.05 ± 1.28 kpa (collagen) 43.81 ± 4.19 kpa (cross-linked) 610.46 ± 56.92 kpa (PDS: cross-linked) 0.24 ± 0.09 (control) 0.62 ± 0.14 (collagen) 0.87 ± 0.17 (collagen-PDS) 0.95 ± 0.15 (control) 1.99 ± 0.23 (collagen) 2.13 ± 0.26 (collagen-PDS) | 0.40 ± 0.11 (Collagen) 2.69 ± 0.47 (cross-linked) 9.08 ± 1.79 (PDS: cross-linked) 5.81 ± 0.99 (control) 9.84 ± 2.24 (collagen) 13.19 ± 1.66 (collagen-PDS) 19.62 ± 1.39 (control) 26.71 ± 2.32 (collagen) 26.88 ± 2.92(collagen-PDS) | 0.40 ± 0.11 (collagen) 2.69 ± 0.47 (cross-linked) 9.08 ± 1.79 (PDS: cross-linked) | 98.55 ± 7.23 (collagen) 61.34 ± 4.71 (cross-linked) 14.81 ± 1.28 (PDS: cross-linked) 20.45 ± 2.3 (control) 13.82 ± 0.91 (collagen) 12.84 ± 0.71 (collagen-PDS) 17.38 ± 2.33 (control) 10.99 ± 1.05 (collagen) 9.91 ± 0.83 (collagen-PDS) | 3.39 ± 0.54 (control) 24.37 ± 2.03 (collagen) 31.87 ± 3.8 (collagen-PDS) 11.7 ± 2.01 (control) 64.91 ± 5.06 (collagen) 78.15 ± 4.42 (collagen-PDS) | 10.82 ± 3.91 (control) 63.72 ± 2.99 (collagen) 81.42 ± 7.84 (collagen-PDS) 31.42 ± 5.77 (control) 129.9 ± 16.07 (collagen) 152.9 ± 8.15 (collagen-PDS) |
| Chen et al. (2017) | Achilles tendon | In vivo rabbit | Sheath and core | Collagen type I/PDS | — | Bovine platelet gel (BPG) | — | — | — | — | — | — | — | — | — |
| Cai et al. (2018b) | Transition/achilles tendon | In vivo rat | Dual-layer aligned and random | SF/P (LLA-CL) | — | — | 445 ± 180 nm (aligned layer) 486 ± 142 nm (random layer) | — | Transplant after 6 weeks transplant after 12 weeks | — | — | — | — | 9.9 ± 1.9 (ARS) 9.3 ± 1.4 (RS) 5.8 ± 1.3 (control]) 21.5 ± 3.5 (ARS) 15.6 ± 1.6 (RS) 10.0 ± 1.1 (control) | 43.9 ± 7.5 (ARS) 41.4 ± 5.7 (RS) 25.3 ± 5.9 (control]) 83.2 ± 12.4 (ARS) 66.2 ± 6.6 (RS) 50.6 ± 3.5 (control) |
| Madhurakkat Perikamana et al. (2018) | Transition/tendon | In vivo rat | Aligned and random | PLLA/ PD | ADSCs | PDGF-BB | ∼600 nm | — | |||||||
| He et al. (2021) | Transition/tendon | In vitro | Aligned and random | PCL)/HA/ZnO | MC3T-E1/ATDC5/Mouse primary fibrochondrocyte/Mouse primary tenocytes | — | — | — | — | — | — | — | — | — | — |
| Haoxuan Li et al. (2020) | Transition/tendon | In vitro | Electrospinning | PLGA | — | — | 428 ± 124 nm | — | As fabricated | — | — | 33.6 ± 8.2 (pristine PLGA) 56.1 ± 10.1 (welded PLGA) | — | — | — |
| Guner et al. (2020) | Tendon | In vitro | Dual core-shell nanofiber scaffolds | PCL/Gelatin | hADSCs | GDF-5 | 5.925 ± 3.23 μm (PCL) 1.715 ± 0.7 μm (PCL/gelatin) | 76.7 ± 9.8 (FSPCL) 63.1 ± 5.3 (FSPCL/ESPCL) 66 ± 3.4 (FSPCL/ESPCLGel) 79.3 ± 4.4 (ESPCL) 81.4 ± 5.7 (ESPCL Gel) | As-fabricated | ∼30.8 (FSPCL) ∼34.5 (FSPCL/ESPCL) ∼33.5 (FSPCL/ESPCLGel 3:1) | ∼32 (FSPCL) ∼41 (FSPCL/ESPCL) ∼41 (FSPCL/ESPCLGel 3:1) | ∼23.5 (FSPCL) ∼26.5 (FSPCL/ESPCL) ∼27.5 (FSPCL/ESPCLGel 3:1) | — | — | — |
| Wu et al. (2021) | Tendon | In vitro | wavy nanofibrous scaffolds | PPDO/SF | hADMSCs/hTCs | — | 526 ± 227 nm (PPDO WNSs) 531 ± 224 nm (4/1 PPDO/SF WNSs) 591 ± 233 nm (2/1 PPDO/SF WNSs) | — | As-fabricated | 15 ± 4 (PPDO WNSs) 28 ± 7 (4/1 PPDO/SF WNSs) 43 ± 6 (2/1 PPDO/SF WNSs) | 31 ± 1 (PPDO WNSs) 25 ± 1 (4/1 PPDO/SF WNSs) 17 ± 1 (2/1 PPDO/SF WNSs) | — | — | — | — |
| Yang et al. (2022) | Transition/tendon | In vivo rat | Electrospinning | PLA/ZIF-11/HKUST-1 | — | — | ∼1μm | — | As-fabricated | 42.14 ± 3.7 (PLA-H/Z) 15.8 ± 2.5 (PLA) 9.2 ± 0.9 (PLA-Z) 11.4 ± 1.8 (PLA-H) | 2059.0 ± 14.5 KPa (PLA-H/Z) 867.5 ± 113.3 KPa (PLA) 555.9 ± 61.8 KPa (PLA-Z) 824.9 ± 52.4 KPa (PLA-H) | — | — | — | — |
| Russo et al. (2020) | Tendon | In vitro | Aligned and Random | PLGA | oAECs | — | 2.5 ± 0.27 μm aligned 2.1 ± 0.19 μm random | — | As-fabricated | — | 26 ± 1.75 aligned 15 ± 0.87 random | — | 344 ± 24.89 aligned 240 ± 12.34 random | — | — |
| Chen et al. (2021c) | Tendon | In vitro | Aligned and random sheath | PCL /HA (core) | Tenocytes of rabbits | PRP (core) | 410 ± 96 nm (random) 483 ± 116 nm (random + core) 362 ± 138 nm (aligned + core) | 83.1 ± 5.6 (random) 86.8 ± 1.8 (random + HA/PRP core) 69.4 ± 3.6 (aligned + HA/PRP core) | As-fabricated | 8.90 ± 0.88 (random) 18.64 ± 4.08 (random + core) 76.02 ± 9.21 (aligned + core) | 2.21 ± 0.99 (random) 1.61 ± 0.51 (random + core) 6.62 ± 0.21 (aligned + core) | — | 31.3 ± 1.4 (random) 23.63 ± 1.1 (random + core) 45.65 ± 1.0 (aligned + core) | — | — |
| Ramos et al. (2019) | Tendon | In vitro | Electrospinning | PCL/CA | hUMSCs | Insulin | 732 ± 335 nm (PCL) 886 ± 426 nm (PCL + 25% CA) 724 ± 350 nm (PCL + 50% CA) 474 ± 305 nm (PCL + 75% CA) | — | As-fabricated | — | — | — | — | — | 10.79 ± 1.49 (PCL) 6.53 ± .48 (PCL + 25% CA) 5.33 ± .82 (PCL + 50% CA) 2.90 ± 0.42 (PCL + 75% CA) |
| Sarıkaya and Gümüşderelioğlu, (2021) | Tendon | In vitro | Aligned | SF/P3HB | rAdMSCs | GDF-5 | 699 ± 203 nm | — | As-fabricated Scaffolds of seeded Cell after 21 days of culture | 197 ± 8 (SF/P3HB) 182 ± 17 (S-SF/P3HB) 56.8 ± 1.5 (A-SF/P3HB) 42.5 ± 6.3 (A-SF/P3HB + GDF-5) | 7.7 ± 0.4 (SF/P3HB) 7.3 ± 0.7 (S-SF/P3HB) 1.9 ± 0.2 (A-SF/P3HB) 2.0 ± 0.1 (A-SF/P3HB + GDF-5) | — | 52.7 ± 3.0 (SF/P3HB) 54.1 ± 3.2 (S-SF/P3HB) 64 ± 1 (A-SF/P3HB) 56 ± 3 (A-SF/P3HB + GDF-5) | 2.33 ± 0.18 (SF/P3HB) 2.27 ± 0.16 (S-SF/P3HB) 1.0 ± 0.2 (A-SF/P3HB) 0.9 ± 0.4 (A-SF/P3HB + GDF-5) | — |
| Yuan et al. (2016) | Tendon | In vitro | Aligned Photo-crosslinked | PCL/PTMC-MA | mMSCs | ∼600 nm | As-fabricated before Photo-crosslinked after Photo-crosslinked | 11.16 ± 0.55 (PCL) 15.26 ± 2.37 [PCL/PTMC-MA (3:1)] 17.00 ± 1.22 [PCL/PTMC-MA (1:1)] 19 ± 3.42 [PCL/PTMC-MA (1:3)] 31.13 ± 1.30 [PCL/PTMC-MA (1:3)] | 4.96 ± 0.94 (PCL) 8.35 ± 1.24 [PCL/PTMC-MA (3:1)] 10.31 ± 1.82 [PCL/PTMC-MA (1:1)] 13.21 ± 0.47 [PCL/PTMC-MA (1:3)] 23.80 ± 3.44 [PCL/PTMC-MA (1:3)] | — | 77 ± 10 (PCL) 126 ± 22 [PCL/PTMC-MA (3:1)] 149 ± 12 [PCL/PTMC-MA (1:1)] 159 ± 9 [PCL/PTMC–MA (1:3)] 170 ± 22 [PCL/PTMC-MA (1:3)] | ||||
| Sensini et al. (2021a) | Tendons and Ligaments | In vitro | Aligned and random | Nylon 6 | — | — | 0.21 ± 0.05 µm (2,500 rpm) 0.23 ± 0.06 µm (1,750 rpm) 0.24 ± 0.06 µm (1,000 rpm) | — | As-fabricated | 1.1 ± 0.23 (1,000 rpm) 2.7 ± 0.49 (1,750 rpm) 4.4 ± 0.78 (2,500 rpm) | — | 1.9 ± 0.53 (1,000 rpm) 4.6 ± 1.2 (1,750 rpm) 6.5 ± 1.6 (2,500 rpm) | 2.8 ± 0.25 (1,000 rpm) 3.4 ± 0.36 (1,750 rpm) 3.1 ± 0.37 (2,500 rpm) | — | — |
| Lim et al. (2021) | Tendons and ligaments | In vitro | Aligned | PCL/gelatin | — | — | 200–800 nm | — | — | — | — | — | — | — | — |
| El Khatib et al. (2021) | Tendons | In vitro | Aligned | PLGA | oAECs | — | 1.33 ± 0.17 µm | — | As-fabricated | ∼400 (0 W) ∼200 (20 W) | - | ∼38 (0 W) ∼17 (20 W) | ∼100 (0 W) ∼10 (20 W) | — | — |