Cell & Stem Cell Research

Due to the limited capacity of current reconstruction procedures, there exists a need for new augmentation matrices to improve the biological fixation to obtain a scarless healing at the tendon-bone (TB) interface. The objectives of this study are to 1) fabricate electrospun polycaprolactone (PCL)-based scaffolds containing transforming growth factor (TGF)β3, connective tissue growth factor (CTGF) and nano-hydroxyapatite (nHA), where concentrations of CTGF and nHA change in opposite directions, while TGF-β3 is located in the middle portion of the nanofibrous composites [such organization is expected to contribute to generation of tendon (in CTGF rich zone), fibrocartilage (by TGFβ3) and bone (in nHA rich zone) upon positioning the scaffold in proper zones], 2) establish controlled release of TGFβ3 and CTGF from nanofiber scaffolds, and 3) to investigate human Bone Marrow Stem Cell (h-BMSC) behavior on these scaffolds. Such a design is proposed for the first time, and represents a significant departure from the conventional stratified approach, and is expected to contribute to scar-free TB interface regeneration. Findings show that linearly varying nHA distribution can be accomplished across the scaffold thickness that is also the case in native TB interface. Results also demonstrated that TGFβ3 and CTGF can be incorporated into nanofiber scaffolds with electrospinning, retain its bioactivity, and released in a sustained manner. The h-BMSCs proliferated similarly on graded and individual scaffolds at the end of 14 days. Collagen production by hBMSCs on different scaffold groups did not lead to any significant differences. This study not only reveals the importance of design and use of biomimetic scaffolds in tissue engineering but also yields new insights into the effect of bioactive molecules on interface regeneration by controlling their local availability.