Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems

TLDR

Tendon tissue engineering using a biomaterial scaffold that mimics the native extracellular matrix and supports autologous adipose‑derived stem cells offers a promising alternative to slow, sub‑optimal autograft or allograft repairs, especially for challenging zone II flexor tendon injuries. We investigated the effect of GDF‑5 on proliferation and gene expression of primary rat ADSCs cultured on a PLAGA electrospun fiber scaffold versus a PLAGA 2D film. GDF‑5 treatment on the PLAGA fiber scaffold markedly upregulated scleraxis (7–8× at week 1, higher at week 2) and collagen I (≈4× from week 1 onward), producing a soft, collagenous tissue that meets tendon regeneration requirements.

Abstract

Tendon tissue engineering with a biomaterial scaffold that mimics the tendon extracellular matrix (ECM) and is biomechanically suitable, and when combined with readily available autologous cells, may provide successful regeneration of defects in tendon. Current repair strategies using suitable autografts and freeze-dried allografts lead to a slow repair process that is sub-optimal and fails to restore function, particularly in difficult clinical situations such as zone II flexor tendon injuries of the hand. We have investigated the effect of GDF-5 on cell proliferation and gene expression by primary rat adipose-derived stem cells (ADSCs) that were cultured on a poly(DL-lactide-co-glycolide) PLAGA fiber scaffold and compared to a PLAGA 2D film scaffold. The electrospun scaffold mimics the collagen fiber bundles present in native tendon tissue, and supports the adhesion and proliferation of multipotent ADSCs. Gene expression of scleraxis, the neotendon marker, was upregulated seven- to eightfold at 1 week with GDF-5 treatment when cultured on a 3D electrospun scaffold, and was significantly higher at 2 weeks compared to 2D films with or without GDF-5 treatment. Expression of the genes that encode the major tendon ECM protein, collagen type I, was increased by fourfold starting at 1 week on treatment with 100 ng mL(-1) GDF-5, and at all time points the expression was significantly higher compared to 2D films irrespective of GDF-5 treatment. Thus stimulation with GDF-5 can modulate primary ADSCs on a PLAGA fiber scaffold to produce a soft, collagenous musculoskeletal tissue that fulfills the need for tendon regeneration.