Preclinical Studies on Biomaterial Scaffold use in Knee Ligament Regeneration: A Systematic Review

Background: Knee joint trauma may result in damage of the intra-articular ligaments, with rupture of the anterior cruciate ligament (ACL) a common and troublesome injury due to poor capabilities for spontaneous regeneration. Autograft and allograft surgical reconstructions are the mainstay of treatment, but have associated risks of failure, therefore tissue-engineering techniques aiming to regenerate the native ACL are being researched as a potential alternative treatment. Objectives: This article aims to review the current evidence produced by ex vivo and in vivo studies investigating biomaterial scaffolding and mesenchymal stem cell (MSC) techniques in orthopaedic tissue engineering of ACL injuries. Methods: Databases searched were Ovid MEDLINE, Cochrane Library, Embase, Elsevier Scopus, Web of Science and NCBI PubMed, with search terms ‘ligament’, ‘scaffold’, ‘mesenchymal stem cell’ and ‘tissue engineering’. Results: 1132 articles were identified, with 19 articles suitable for review inclusion. Of the eligible studies, 10 used biologic scaffold material, 6 used synthetic constructs, and hybrid scaffolds were employed in the remaining 3 studies. Conclusions: A large amount of preclinical evidence for viability of MSC seeded biomaterial scaffolds in ACL regeneration exists. Studies show that with stimulation, MSCs adhere and proliferate well on various scaffold materials ranging from silk to engineered polymers. Hybrid scaffolds are particularly promising, and with further research, the best features from strong natural substances such as silk, and biologically inert synthetic materials could be combined. Currently, there are few plans to begin human clinical trials, but preclinical studies are moving into larger animal models. Keywords: Knee, ligament, mesenchymal stem cells, preclinical, scaffold, tissue engineering, regeneration.