A Route to Translate a Silk-Based Medical Device from Lab to Clinic: The Silk Biomaterials Srl Experience

SIMPLE SUMMARY: Silk has always been a source of inspiration for textile designers to create very disruptive fashion products. More recently, silk has stimulated the creativity of scientists, as it emerged as a promising biomaterial for the development of next generation medical devices. Although silk has been clinically used as a suture for decades, only the development of novel processing approaches paved the way for the production of a plurality of regenerated silk-based materials, i.e., films, hydrogels, sponges, powder, nano- and microparticles, nanofibers, etc., which have been recognized as scaffolds-of-choice in different medical applications. However, the translation of research achievements into medical products used in clinical settings is complex from manufacturing, quality, and regulatory perspectives. The aim of this paper is to disclose how the clinical translation route works using, as a case study, a silk-based medical device recently developed by the Italian start up Silk Biomaterials srl. The results reported here will cover some fundamental aspects of the regulatory and quality path, from the demonstration of the robustness of the manufacturing process up to the evaluation of the biocompatibility, and of the functional performance of the device. ABSTRACT: The medical device is a nerve conduit entirely made of Bombyx mori silk fibroin. It is a tubular scaffold used for repairing peripheral nerve gaps, whose function is to protect the severed nerves and to favor their natural healing process. As any implantable medical device, the conduit must perform its function without causing adverse effects to the patient, meaning that it must be compliant with a range of regulations aimed at evaluating the risks related to the constituent materials and the manufacturing process, the toxicological impact of the processing aids, the biological safety, the functional performance, and the ability to sustain tissue regeneration processes. An exhaustive on-bench testing plan has been performed for the determination of the morphological, geometrical, physical, structural, and mechanical properties. For the toxicological analysis, the device was extracted with solvent and the number of leachable substances was determined by suitable chromatographic techniques. The biological safety was assessed by means of a set of tests, including cytotoxicity, delayed hypersensitivity, intracutaneous reactivity, pyrogen test, LAL (Limulus Amebocyte Lysate) test, acute systemic toxicity, and genotoxicity. Overall, the accumulated results demonstrated the suitability of the device for the intended use and supported the starting of a first-in-human clinical trial.