Design and optimization of a bioresorbable polymeric hierarchical ligament fascicle substitute for anterior cruciate ligament tissue regeneration

Abstract

There is growing interest in developing a synthetic replacement for the anterior cruciate ligament (ACL). Current replacement options for ACL ruptures utilize autograft or allograft tissues which have limitations that include donor site morbidity, limited supply, risk of disease transfer and immunogenic response after implantation. This "gold standard" leaves room for a synthetic alternative that offers comparable mechanical strength to native tissue, as well as the added possibility of providing chemical cues that promote neo-tissue formation and regeneration of a healthy tissue type.

Knowledge gained from this project contributes to the fields of regenerative medicine and tissue engineering, and in the future can be applied to the development of ligament or tendon replacement scaffolds.

This work demonstrates the production of a synthetic ligament fascicle substitute bundle that is biocompatible and encourages the growth and regeneration of ligament tissue. Research and development utilizes polymer fabrication techniques, extrusion and electrospinning, to create a hierarchical, biomimicing design using poly-l-lactide (PLLA) and polycaprolactone (PCL). The bundle design consists of four individual fascicle substitutes, each with a core extruded PLLA fiber combined with a PCL electrospun nanofiber shell; results show that the mechanical properties of the bundle are dictated by the core fiber material. The novel hierarchical design allows for the incorporation of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) for controlled release from the electrospun nanofibers. When cultured with human mesenchymal stem cells (hMSCs), results show that the composite bundle provides a viable substrate for cell attachment and growth. Gene expression shows that the presence of the novel bundle substrate and the presence of growth factors during in vitro culture conditions allows for the upregulation of ligament markers from hMSCs. The known ligament markers: collagen types I and III, tenascin-C and scleraxis, demonstrated an increase in gene expression during 21 day culture conditions.