The Fabrication and in vitro Evaluation of Retinoic Acid-Loaded Electrospun Composite Biomaterials for Tracheal Tissue Regeneration

Frontiers in Bioengineering and Biotechnology

Brenton Cavanagh¹  Ivana Ivankovic³  Cian O'Leary³  Luis Soriano³  Aidan Fagan-Murphy³  Sally-Ann Cryan⁶  Fergal J. O'Brien⁶ 

[1] Cellular and Molecular Imaging Core, Royal College of Surgeons in Ireland, Dublin, Ireland;SFI Advanced Materials and Bioengineering Research (AMBER) Center, Royal College of Surgeons in Ireland and Trinity College Dublin, Dublin, Ireland;SFI Center for Research in Medical Devices (CÚRAM), Royal College of Surgeons in Ireland, Dublin, Ireland;School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland;Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland;Trinity Center for Biomedical Engineering, Trinity College Dublin, Dublin, Ireland;

关键词: tracheal regeneration;    retinoic acid;    polycaprolactone;    chitosan;    biomaterials;    mucociliary epithelium;   

DOI  :  10.3389/fbioe.2020.00190

来源: DOAJ

【 摘 要 】

Although relatively rare, major trauma to the tracheal region of the airways poses a significant clinical challenge with few effective treatments. Bioengineering and regenerative medicine strategies have the potential to create biocompatible, implantable biomaterial scaffolds, with the capacity to restore lost tissue with functional neo-trachea. The main goal of this study was to develop a nanofibrous polycaprolactone-chitosan (PCL-Chitosan) scaffold loaded with a signaling molecule, all-trans retinoic acid (atRA), as a novel biomaterial approach for tracheal tissue engineering. Using the Spraybase® electrospinning platform, polymer concentration, solvent selection, and instrument parameters were optimized to yield a co-polymer with nanofibers of 181–197 nm in diameter that mimicked tracheobronchial tissue architecture. Thereafter, scaffolds were assessed for their biocompatibility and capacity to induce mucociliary functionalization using the Calu-3 cell line. PCL-Chitosan scaffolds were found to be biocompatible in nature and support Calu-3 cell viability over a 14 day time period. Additionally, the inclusion of atRA did not compromise Calu-3 cell viability, while still achieving an efficient encapsulation of the signaling molecule over a range of atRA concentrations. atRA release from scaffolds led to an increase in mucociliary gene expression at high scaffold loading doses, with augmented MUC5AC and FOXJ1 detected by RT-PCR. Overall, this scaffold integrates a synthetic polymer that has been used in human tracheal stents, a natural polymer generally regarded as safe (GRAS), and a drug with decades of use in patients. Coupled with the scalable nature of electrospinning as a fabrication method, all of these characteristics make the biomaterial outlined in this study amenable as an implantable device for an unmet clinical need in tracheal replacement.

【 授权许可】

Unknown