Table 2.
New repair proposals for tendon injuries
| New proposals | Type of material | Study model | Outcome | Reference |
|---|---|---|---|---|
| Stem cells | Tendon-derived stem cells (TDSC) | Rat; patellar tendon; surgical window defect, 1 mm in width; TDSC-fibrin constructs transplantation; analysis at 2, 4 and 8 wks. | The treated TDSCs accelerated and enhanced the quality of tendon repair compared with untreated TDSCs up to week 8, which was better than that in the controls up to week 16 as shown by histology, ultrasound imaging and biomechanical testing. | Lui et al99 Lui et al99 |
| Periodontal ligament cells (PDL), Achilles tendon-derived cells | Rat; Achilles tendon; surgical transection 3 mm; 3D cell pellet transplantation; analysis at 16 weeks. | PDL group showed advanced tissue maturation, less ectopic fibrocartilage formation, more organised collagen fibres, tendon matrix expression corresponding to the final healing stage, and better cell morphometry parameters when compared with the control group. | Hsieh et al100 | |
| Human mesenchymal stem cells (hMSC) and scleraxis (hMSC-Scx) -programmed tendon progenitors | Rat; Achilles tendon; surgical transection 3 mm; 3D cell pellet transplantation; analysis at 16 weeks. | Implantation of hMSC-Scx, in contrast to hMSC and empty defect, results in smaller diameters, negligible ectopic calcification and advanced cellular organisation and matrix maturation in the injured tendons. | Hsieh et al101 | |
| Rat bone marrow mesenchymal (BMSC) and tendon-derived stem cells | Rat; Achilles tendon; surgical transection 5 mm; TDSCs or BMSCs were injected; analysis at 1, 2 and 4 wks. | TDSCs showed better biomechanical properties and higher tendency in Col-I/III gene expression level during wks 1 and 2. Immunofluorescent assay revealed higher expression of Tenascin-C in TDSCs at week 1. |
Al-ani et al102 | |
| Human embryonic stem cell-derived mesenchymal stem cells (MSC) | Rat; Achilles tendon; surgical transection 1.5-7.5 mm; Knitted Silk-Collagen Scaffold loaded with human embryonic stem cell-derived MSC; analysis at 2 and 4 weeks. | Enhanced regeneration process as shown by histological scores; superior mechanical performance but still much lower than normal tissues. | Chen et al103 | |
| Rat BMSC. | Rat; Achilles tendon; surgical transection 2 mm; MSC injection; analysis at 2 and 4 wks. | Partially positive effects on tendon remodelling in the initial stages by biomechanical test; negative or negligible effects on biomechanical results of tendon remodelling. | Kraus et al104 | |
| Rat MSC | Rat; Achilles tendon; surgical transection 3 mm proximally; MSC-loaded mesh; analysis at days 6 and 14 | Histology showed that at day 6 dense and parallel collagen bundles; reduced vascularity and increased type I collagen, better collagen formation and organisation at day 14. | Shon et al105 | |
| Human induced pluripotent stem cells (iPSC)-derived neural crest stem cells (iPSC-NCSCs) | Rat; patellar tendon; standardised full-thickness window defect (1*4 mm); defect filled with fibrin gel with iPSC-NCSCs; analysis at 1, 2 and 4 weeks. | Superior repair performance in macroscopical observation; significantly enhancement in histological and mechanical examinations. | Xu et al106 | |
| Rat tendon-derived stem cells | Rat; patellar tendon; surgical transection 1 mm; TDSCs-fibrin construct was placed in defect; analysis at 1, 2 and 4 weeks. | Better haematoxylin stain in results showing improved histomerphology; The ultimate stress and the Young’s modulus were significantly higher in the TDSCs group at week 4. | Ni et al107 | |
| Biomaterials | Type I collagen sponge | Rat; Achilles tendon; surgical transection; analysis at 1, 2 and 4 wks. | Defects receiving collagen sponges showed improved healing, with significantly stronger and less stiff tendons than control tendons. No inflammatory reaction due to the collagen sponge was found histologically. | Müller et al108 |
| Collagen-elastin scaffold | Rabbit flexor tendon; surgical cut; analysis at 3 and 8 wks. | Greater gapping after 3 wks; enhances both cellular and extracellular inflammation. | Wichelhaus et al109 | |
| Ovine forestomach matrix (OFM) scaffold | Rat; rotator cuff, surgical transection; OFM scaffolds (5 mm × 10 mm) were overlaid longitudinally on the superficial aspect of the tendon-bone insertion; analysis at 6 days and 12 wks. | Improved healing quality was shown by histological analysis, no evidence of excessive inflammatory response, no biomechanical advantage of augmentation. | Street et al110 | |
| Silk and collagen scaffolds | Mice; Achilles tendon; surgical defect; analysis at 10 days and 24 wks. | A thick, cylindrical, greyish fibrous structure and a shiny white tendon appearance were observed which are more clos to native tendons. | Know et al111 | |
| Nanofiber scaffold (6 layers of polyglycolic acid and 5 layers of fibrin) | Dog; flexor tendon; surgical transection; adipose-derived mesenchymal stem cells and growth factors seeded scaffolds were sutured in between the transection; analysis at 0 and 9 days. | Cell viability showed no significant decreases, growth factor release was higher in scaffold treated group; no obvious inflammatory response was observed on histology. | Manning et al112 | |
| Purified Collagen I Oriented Membrane | Rabbit; patellar tendon surgical transection; collagen membrane was sutured to the upper and lower patellar pole and at the paramedian level; analysis at 1 and 6 months. | Histological findings showed satisfactory graft integration with native tendon; histological examination also showed ongoing angiogenesis. | Gigante et al113 | |
| Collagen fibre implant | Sheep; patellar tendon; surgical transection 4 mm; implant was sutured in between the transaction with tension; analysis at 3 and 6 mnths. | Histology showed better integration, mechanical test showed no statistically difference in stress to failure. | Enea et al114 | |
| Growth factors | Rabbit platelet-rich plasma (PRP) | Rabbit; patellar tendon; full-thickness surgical defect; PRP with the gel form were placed in the defect; analysis at 1, 2, 3 and 4 wks. | Stronger and more extensive expression of TGF-b1 was showed at 1 and 2 wks by immunohistochemistry. | Lyras et al115 |
| Basic fibroblast growth factor | Rat; Achilles tendon; surgical defect; analysis at 12 weeks | Biomechanical properties were not significantly improved. | Kraus et al116 | |
| Bone morphogenetic protein 12 (BMP 12) | Dog; flexor digitorum profundus tendon; surgical transection; 5 mm depth, 2.5 mm width; scaffold with adipose derived stromal cells and BMP 12 were placed in the transection; analysis at 28 days. | Tensile properties showed no significantly difference; proteomics analysis showed amplification of inflammation, stress response and matrix degradation. | Gelberman et al117 | |
| Recombinant human platelet-derived growth factor | Rat; rotator cuff; surgical transection; collagen scaffold; analysis at 5 days and 28 days. | A dose-dependent response in cellular proliferation and angiogenesis was observed. | Kovacevic et al118 | |
| Rat PRP | Rat; rotator cuff tendon; surgical transection; analysis at 8 wks. | No complications related to the surgery or PRP application were observed; both failure loads and displacement were significantly higher in the two PRP-treated groups. | Ersen et al119 | |
| Rabbit PRP | Rabbit; patellar tendon; surgical transection; PRP was applied to the repair site; analysis at 2, 4 and 8 wks. | Mechanical properties showed no significant difference, no difference in collagen content or maturity was detected. | Kollitz et al120 | |
| Rat PRP | Rat; rotator cuff tendon; surgical transection; analysis at 3 wks. | Higher maximal load and stiffness, better Bonar score. | Dolkart et al121 |