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Table 2 Hydrogel-based studies on tendon tissue engineering

From: Boosting tendon repair: interplay of cells, growth factors and scaffold-free and gel-based carriers

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