Could an Anterior Cruciate Ligament Be Tissue-Engineered from Silk?

Abstract

Silk has a long history as an exclusive textile, but also as a suture thread in medicine; nowadays, diverse cell carriers are manufactured from silk. Its advantages are manifold, including high biocompatibility, biomechanical strength and processability (approved for nearly all manufacturing techniques). Silk’s limitations, such as scarcity and batch to batch variations, are overcome by gene technology, which allows for the upscaled production of recombinant “designed” silk proteins. For processing thin fibroin filaments, the sericin component is generally removed (degumming). In contrast to many synthetic biomaterials, fibroin allows for superior cell adherence and growth. In addition, silk grafts demonstrate superior mechanical performance and long-term stability, making them attractive for anterior cruciate ligament (ACL) tissue engineering. Looking at these promising properties, this review focusses on the responses of cell types to silk variants, as well as their biomechanical properties, which are relevant for ACL tissue engineering. Meanwhile, sericin has also attracted increasing interest and has been proposed as a bioactive biomaterial with antimicrobial properties. But so far, fibroin was exclusively used for experimental ACL tissue engineering approaches, and fibroin from spider silk also seems not to have been applied. To improve the bone integration of ACL grafts, silk scaffolds with osteogenic functionalization, silk-based tunnel fillers and interference screws have been developed. Nevertheless, signaling pathways stimulated by silk components remain barely elucidated, but need to be considered during the development of optimized silk cell carriers for ACL tissue engineering.

Review of Spider Silk Applications in Biomedical and Tissue Engineering

“…The analysis showed that spider silk tissue outperforms ACL, thanks to its exceptional mechanical resistance, as it can withstand stresses of up to 2.5 MPa [ 145 ]. However, only experimental research still exists for the use of fibroin in ACL grafts, without clinical trials [ 25 ], even though research results are very promising [ 146 ]. Scaffolds made of silk that exhibit osteogenic function, interference screws, and tunnel fillers have been prototyped, with further research related to the stimulation of signaling pathways [ 25 ].…”

“…However, these traditional treatments do not regenerate cartilage, just relieve patients of pain, unlike novel biomaterials with silk fibroin that can mimic the tissue structure and promote cartilage regeneration and new tissue growth [ 10 ]. Ligament tissue regeneration is complex and still under research, whereas silk-based materials show great promise [ 25 ]. For the repair of damaged intervertebral discs by using silk (hydrogels with silk and silk-based scaffolds), preclinical studies have shown excellent results [ 26 ], but clinical studies are still missing.…”