Table 2.
Hydrogel-based studies on tendon tissue engineering
| Hydrogel | Cell type | Cell proliferation and vitality | Gene expression and ECM | Biomechanical analyses | Study type, animal species and delivery method | Reference |
|---|---|---|---|---|---|---|
| Collagen/Fibrin | TSPCs | Not studied | TSPCs in the fibrin hydrogel exhibited significant upregulation of tenogenic markers (Scx, TnC, and F-mod) in comparison to Col gel. Tissue engineering constructs based on fibrin with TSPCs showed better collagen alignment compared to Col hydrogel. | Tissue engineered construct based on fibrin hydrogel showed higher linear stiffness than Col gel at day 10. However, no significant difference was detected at day 14. | In vitro | Breidenbach et al. 2015 |
| Fibrin | BMSCs | Over 90% of labeled BMSCs remained viable after mixing in the fibrin hydrogel. | BMSCs continued to express the original phenotypic profile. Notably, all cells showed an absence of CD14, CD34, and CD45 expression. In addition, they maintained expression of CD105, CD73, and CD90. | At 2 weeks, there was a significant increase in stiffness of repaired tissue in the cell-treated group compared with the control group. However, at 4 weeks, this effect dissipated because both groups showed similar stiffness. | Athymic rat; Surgery | Degen et al. 2016 |
| Fibrin | TSPCs | The cell proliferation rate in the TSPCs group treated with CTGF and ascorbic acid was lower compared with control group. | Not studied. | The transplantation of TSPC-fibrin constructs promoted tendon repair up to week 16, while TSPC that were pre-treated with CTGF showed better results already at 8. Both the ultimate stress and maximum Young’s modulus increased at a faster rate in the CTGF- treated TSPC group compared with the untreated group. | In vitro; Rat; Surgery | Lui et al. 2016 |
| HA | Tendon fibroblasts | HA significantly decreased cell proliferation in a dose-dependent manner. | Immunofluorescence cytochemistry detected constitutive binding of HA and CD44 receptor on the tendon-derived cells. The expression levels of pro-collagen I α1 was not significantly decreased, but, the expression of procollagen III α1 was decreased significantly in a dose-dependent manner. | Not studied. | In vitro | Yamada et al. 2007 |
| Tendon ECM | ADSCs | Spindle shaped cells were observed both on the gel surface as well as within the gels, with a homogenous distribution of cells throughout the gel. | Gene expression was not studied. This ECM gel solution can be delivered percutaneously into the zone of tendon injury in a rat model. After injection, the thermos-responsive behaviour of the ECM solution will allow it to gelate at body temperature. A supportive nanostructure of collagen fibres can be established to fit the three-dimensional space of the defect. | Not studied. | Rat; Injection | Farnebo et al. 2014 |
| Tendon ECM | ADSCs | Proliferation rate of ADSC in tendon ECM-derived hydrogel treated with PRP was higher than untreated group. | Gene expression was not studied. Upon histological analysis, Hematoxylin and Eosin staining showed increased extracellular matrix formation in groups containing PRP and increased cellularity in groups containing ADSCs. | Mean ultimate failure load was increased in hydrogels augmented with PRP group at 2 weeks. At 4 weeks, hydrogel alone reached a similar mean ultimate failure load to hydrogels augmented with PRP and ADSCs. However, at 8 weeks, hydrogels with PRP and ADSCs demonstrated increased strength over other groups. In conclusion, groups containing both PRP and ASCs encouraged earlier mechanical strength and functional restoration. | Rat; Surgery | Chiou et al. 2015 |