Tendon Regeneration with Tendon Hydrogel–Based Cell Delivery: A Comparison of Fibroblasts and Adipose-Derived Stem Cells

Abstract

Background: Tendon hydrogel is a promising biomaterial for improving repair strength after tendon injury. This study compares the capacity of fibroblasts and adipose-derived stem cells to proliferate, survive, and acquire tenogenic properties when seeded into tendon hydrogel in vitro and in vivo. Methods: The effect of cell density on hydrogel contraction was measured macroscopically. To assess tenogenic properties, RNA was isolated from cells seeded in vitro in hydrogel, and tenocyte markers were quantified. To assess in vitro proliferation and survival, MTS and live-dead assays were performed. Finally, to assess the in vivo survival of cells in hydrogel, subcutaneous injections were performed on rats and in vivo imaging was performed. Results: At 0.5 million cells/ml, both the fibroblasts and adipose-derived stem cells induced minimal hydrogel contraction compared with higher cellular concentrations. Fibroblasts and adipose-derived stem cells seeded at 0.5 million cells/ml in tendon hydrogel up-regulated several tenocyte markers after 1 week. On MTS assay, fibroblasts and adipose-derived stem cells proliferated in hydrogel at similar rates. On live-dead assay, fibroblasts survived longer than adipose-derived stem cells. With use of the in vivo imaging system and histologic evaluation, fibroblasts survived longer than adipose-derived stem cells in hydrogel in vivo. Conclusions: Tendon healing is mediated by the proliferation, survival, and tenogenic differentiation of cells at the site of injury. Tendon hydrogel delivering dermal fibroblasts may improve and stimulate this process compared with adipose-derived stem cells. Future studies will be needed to evaluate the effects of this hydrogel-based cell delivery on chronic tendon injuries.

Direct cellular reprogramming and transdifferentiation of fibroblasts on wound healing—Fantasy or reality?

“…The results showed that fibroblasts survived longer than adipose‐derived stem cells in vivo. Hence, fibroblasts could improve chronic wound healing and are particularly feasible for use in tendon injury 54 …”

“…Hence, fibroblasts could improve chronic wound healing and are particularly feasible for use in tendon injury. 54 …”

Hydrogels in the Treatment of Degenerative Tendinopathy

“…Xu et al [81] developed an injectable fibromodulin-releasing hydrogel for tendon healing that significantly improved the histological results of tendon wound healing and led to the recovery of mechanical properties. Various cell delivery methods, such as hydrogel-based cell delivery, which delivers dermal fibroblasts into the tendon, can enhance and stimulate this process compared to adipose-derived stem cells [82] .…”