Advisory Committee Chair
Advisory Committee Members
Dale S Feldman
Date of Award
Degree Name by School
Doctor of Philosophy (PhD) School of Engineering
The anterior cruciate ligament (ACL) is the most commonly injured ligament of the knee, often requiring orthopedic reconstruction using autograft or allograph tissue, both with significant disadvantages. As a result, tissue engineering an ACL replacement graft has been heavily investigated. The present study attempts to replicate the morphology and mechanical properties of the ACL using a nanomatrix composite of highly-aligned poly(lactic acid) (PLA) fibers with various surface and biochemical modifications. Additionally, this study attempts to recreate the natural mineralization gradient found at the ACL enthesis onto the scaffold, capable of inducing a favorable cellular response in vitro. Unidirectional electrospinning was used to create nanofibers of PLA, followed by an induced degradation of the nanofibers via 0.25M NaOH hydrolysis. The effects of the unidirectional electrospinning as well as the effects of NaOH hydrolysis on fiber alignment, fiber diameter, surface morphology, crystallinity, in vitro swelling, immobilization of fibrin, and mechanical properties were investigated, resulting in a modified morphology correlating to the microstructure of native ligament tissue with similar mechanical properties. Furthering the development of the PLA nanomatrix composite, a bioinkjet printer was used to immobilize nanoparticulate hydroxyapatite (HANP) on the surface of the scaffold. A series of 300pL droplets of HANP bioink were printed over a gradient pattern mimetic of (and spatially corresponding to) the mineralization gradient found over the microanatomy at the ACL enthesis. Proliferation and differentiation response of human mesenchymal stem cells (hMSCs) in vitro was assessed on a variety of conditions and combinations of the PLA nanofiber scaffold surface modifications (inclusive and exclusive of HANP, fibrin, and various time dependent NaOH treatments). It was found that a combinatory effect of the HANP gradient with fibrin on 20 minute NaOH treated PLA nanofibers enhanced the osteogenic differentiation of hMSCs, with an observable morphological change spatially corresponding to the compositional changes of the printed HANP gradient. Using the bioactive scaffold designed in this study as a template and expanding on the methods utilized, future studies can incorporate specific growth factors and other organic/inorganic biomolecules to further develop the engineered PLA nanomatrix into a functional ligament-replacement graft.
Uehlin, Andrew F., "Optimization of a Biomimetic Poly(Lactic Acid) Ligament Scaffold" (2012). All ETDs from UAB. 3190.