Design and optimization of a silk scaffold for ligament engineering.

摘要

A replacement graft for a torn anterior cruciate ligament (ACL) has long been sought that will eliminate the need for harvest of the patient's own tissue preventing donor-site morbidity while adequately restoring knee biomechanics. The objective of this work was to design and optimize a mechanically robust silk-based ACL replacement graft. The present work describes efforts to utilize textile methods to design an appropriate silk fibroin yarn for ligament engineering. It serves to further the understanding of the impact of yarn design and methods of analysis on resultant properties. Those knowledgeable in the area of scaffold design can extrapolate the trends presented here to specific structural and functional needs in tissue engineering. In the case of ligament engineering, a small diameter cabled yarn was identified as the ideal building block of a replacement graft. The load carrying responsibility of a ligament graft must be slowly and predictably transferred to the ingrowing tissue through a degradation and remodeling process. Here, silk fibroin yarns were incubated in Protease XIV to create an in vitro model system of proteolytic degradation. Native fibroin was shown to degrade with predictable rates of change in fibroin diameter, failure strength, cycles to failure, and mass. A mechanism of native silk fibroin yarn degradation was proposed as a result of histomorphometric analysis of two yarn geometries implanted subcutaneously in a rat model. Comparison with the previously developed in vitro model system indicated a positive correlation and demonstrated the usefulness of the in vitro model in accurately predicting the degradation rate of silk yarn. With an understanding of the mechanics and expected degradation rate of the cabled yarn, an appropriate large animal model to assess safety and efficacy was explored. Ingrowth within the ligament graft and within the bone tunnels was observed as early as four weeks post implantation. Pilot scale anterior-posterior laxity and single-pull-to-failure analysis of the silk graft was performed following implantation in a goat model. This study demonstrates the potential of an appropriately engineered silk-based ACL graft to degrade predictably within the complex intra-articular environment of the knee.