Tissue engineering approaches for the repair and regeneration of the anterior cruciate ligament: towards 3D bioprinted ACL-on-chip
1 Tissue Engineering for Orthopaedics and Mechanobiology, Bone and Joint Program, Department for BioMedical Research (DBMR), Medical Faculty, University of Bern, Bern, CH-3008, Switzerland
2 ARTORG Centre for Biomedical Engineering, University of Bern, CH-3008 Switzerland
3 Department of Biomedical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA
4 Orthopaedic Department of the Mediznische Hochschule Hannover (MHH), Annastift, Hannover-Kleefeld, D-30625, Germany
5 Department for Orthopaedic Surgery and Traumatology, Knee Team, Insel University Hospital, Medical Faculty, University of Bern, Bern, CH-3010, Switzerland
Abstract
The anterior cruciate ligament (ACL) is the most frequently injured ligament in the knee. The current method to treat the injured ligament is reconstruction using autografts and allografts. Reconstruction requires the regeneration of ligament, bone and their interface to ensure proper recovery. Recently, researchers have focused on using tissue-engineered scaffolds made of synthetic materials and biomaterials —such as collagen, decellularised tissues, silk and synthetic polymers produced following different manufacturing methods — for ACL reconstruction,. Different materials can be easily processed using various fabrication methods for mimicking the mechanical properties of the ACL. The advances in technologies play an important role in the production of constructions that can mimic native ACL.. The present review addresses integrative scaffold design, different challenges in the potential materials and manufacturing methods as well as future strategies for ACL repair. Furthermore, the review provides a road map to 3D printing combined with organ-on-chip technology to demonstrate the potential for cost-effective and user-friendly fabrication methods for ACL engineering. Finally, it underlines the potential of 3D bioprinting and organ-on-chip technologies for micro-engineering of ligaments and their associated environment.
Graphical Abstract

Keywords
- Anterior cruciate ligament
- 3D (bio)-printing
- relative gene expression
- collagen content
- platelet-rich-plasma
- platelet-rich fibrin
- organs-on-chip
