Hierarchical electrospun tendon-ligament bioinspired scaffolds induce changes in fibroblasts morphology under static and dynamic conditions

Alberto Sensini, Luca Cristofolini, Andrea Zucchelli, Maria Letizia Focarete, Chiara Gualandi, Arianna De Mori, Alex Kao, Marta Roldo, Gordon William Blunn, Gianluca Tozzi

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The regeneration of injured tendons and ligaments is challenging since the scaffolds needs proper mechanical properties and a biomimetic morphology. In particular, the morphological arrangement of scaffolds is a key point to drive the cells growth to properly regenerate the collagen extracellular matrix. Electrospinning is a promising technique to produce hierarchically structured nanofibrous scaffolds able to guide cells in the regeneration of the injured tissue. Moreover, the dynamic stretching in bioreactors of electrospun scaffolds had demonstrated to speed up cell shape modifications in vitro. The aim of the present study was to combine different imaging techniques such as high-resolution X-ray tomography (XCT), scanning electron microscopy (SEM), fluorescence microscopy and histology to investigate if hierarchically structured poly(L-lactic acid) and collagen electrospun scaffolds can induce morphological modifications in human fibroblasts, while cultured in static and dynamic conditions. After 7 days of parallel cultures, the results assessed that fibroblasts had proliferated on the external nanofibrous sheath of the static scaffolds, elongating themselves circumferentially. The dynamic cultures revealed a preferential axial orientation of fibroblasts growth on the external sheath. The aligned nanofiber bundles inside the hierarchical scaffolds instead, allowed a physiological distribution of the fibroblasts along the nanofiber direction. Inside the dynamic scaffolds, cells appeared thinner compared with the static counterpart. This study had demonstrated that hierarchically structured electrospun scaffolds can induce different fibroblasts morphological modifications during static and dynamic conditions, modifying their shape in the direction of the applied loads.
Original languageEnglish
JournalJournal of Microscopy
Early online date24 Jul 2019
Publication statusEarly online - 24 Jul 2019


  • cell culture
  • cell morphology
  • dynamic cell culture
  • electrospinning
  • hierarchical scaffolds
  • high-resolution X-ray tomography
  • ligamentss
  • tendons
  • tissue engineering


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