Biomimetic grafts from ultrafine fibers for collagenous tissues.

Abstract

The ligament is the soft tissue that connects bone to bone and, in case of severe injury or rupture, it cannot heal itself mainly because of its poor vascularity and dynamic nature. Tissue engineering carries the potential to restore the injured tissue functions by utilization of scaffolds mimicking the structure of native ligament. Collagen fibrils in the anterior cruciate ligament (ACL) have a diameter ranging from 20 to 300nm, which defines the physical and mechanical properties of the tissue. Also, the ACL tissue exhibited a bimodal distribution of collagen fibrils. Currently, the ability to fabricate scaffolds replicating this structure is a significant challenge. This work aims at i) measuring the diameter of collagens of bovine ACL tissue, ii) investigating the fabrication of sub-100nm fibers, and iii) fabricating aligned scaffolds with bimodal diameter distribution (with two peaks) resembling the healthy ACL structure. It is hypothesized that such scaffolds can be produced by electrospinning polycaprolactone (PCL) solutions. To test the hypothesis, various PCL solutions were formulated in acetone and formic acid in combination with pyridine, and electrospun to generate sub-100nm fibers. Next, this formulation was adjusted to produce nanofibers with a diameter between 100nm and 200nm. Finally, these solutions were combined in the co-electrospinning process, i.e., two-spinneret electrospinning, to fabricate biomimetic scaffolds with a bimodal distribution. Electrospinning of 8% and 15% PCL solutions, respectively, resulted in the production of fibers with diameters below and above 100nm. The combined scaffold exhibited a bimodal distribution of aligned fibers with peaks around 80 and 180nm, thus mimicking the collagen fibrils of healthy ACL tissue. This research is expected to have a society-wide impact because it aims to enhance the health condition and life quality of a wide range of patients.