Cyclic Stretch Bioreactor Enhances Tenogenic Differentiation of MSCs in Biomimicked PCL-tdECM Membranes through Dynamic Mechanical Loading

Tendon injuries are widespread, often leading to tendinopathy due to a lack of early recognition, resulting in discomfort and reduced mobility. Despite their mechanically active nature, tendons possess limited self-healing capacity, and current clinical interventions fall short in fully regenerating the tendon structure. To address this challenge, we propose an in vitro model to study disease progression and develop an effective tissue regeneration strategy. Here, we show that an electrospun bioactive polymeric membrane comprising poly(ε-caprolactone) (PCL) and goat tendon decellularized extracellular matrix (tdECM) is an ideal polymer-tdECM complex to increase strength and provide native tendon tissue biomolecules crucial for its development. Culturing these membranes with umbilical cord mesenchymal stem cells (uMSCs) under mechanical stimulation in a bioreactor mimics native tissue conditions, which are essential for effective tendon regeneration. The study demonstrates a tissue engineering approach combining dynamic mechanical cues from a bioreactor and biochemical cues from tdECM to induce tenogenesis in uMSCs. Biological results indicate that membranes are biocompatible, and optimal membrane strength and stiffness are retained after 14 days of culture. Furthermore, qPCR and immunofluorescence studies have shown an increase in the number of tenogenic markers in response to biomechanical cues. The synergy between PCL and tdECM presents promising prospects for advancing tendon tissue engineering.