Developing sustained dual-drug therapy for tendon sports injuries

Abstract

Tendon plays an important role in regulating body locomotion and providing additional stability to the body. However, tendon is susceptible to injuries and the healing process could be devastating along with the several issues, namely adhesion formations, slow healing and failure at fixation sites, which have deferred the success of proper tendon healing via tendon tissue engineering. This dissertation thus aims to create a sustained dual-drug therapy to address these issues. For adhesion formation, naproxen sodium (NPS) has been shown to be able to avoid this symptom through inhibiting inflammation process. Therefore, so as to eliminate the side effects of NPS such as drowsiness, headache and nausea, NPS was loaded into an electrospun aligned poly (l-lactic acid)/poly (εcaprolactone) scaffold and its release from the scaffold was optimized to achieve controlled release through adjusting the polymer compositions and water percentage in hexafluoroisopropanol (HFIP). A 2-week sustained release was achieved through modulating the NPS distribution in the fibers of a scaffold which possesses aligned morphology and optimal mechanical properties. Notably, the scaffold exhibited no cytotoxicity and tenocytes could respond to the topographical cues given by the scaffolds, forming a network of cells which mimic the native tendon tissue arrangement. Although NPS is needed to prevent adhesion formations, it has been shown to inhibit the proliferation of tenocytes. Hence the second objective of this dissertation is to release growth factor to promote cell proliferation, and at the same time tackle on the slow healing issues during tendon healing. Insulin-like growth factor 1 (IGF-1) was thus loaded into electrospun poly (lactic-co-glycolic acid)/poly (ε-caprolactone) aligned scaffolds for its ability to promote cellular proliferation and maturation. HFIP was identified as the electrospinning solution for its ability to better maintain IGF-1 stability...