Design, Development and Application of Hybrid Polycaprolactone-Polyphosphazene Electrospun Constructs for the Augmentation of Massive Rotator Cuff Repair

In rotator cuff repair the application of materials into the repair site, known as augmentation, can significantly increase the strength of repairs. The first part of this dissertation focused on combining electrospun polycaprolactone (PCL) with poly[(ethyl alanato)1(p-methyl phenoxy)1] phosphazene (PNEA-mPh) into a novel fibrous augmentation device. Coating with 1%, 2% and 3% (weight/volume) polyphosphazene solutions resulted in roughened surfaces that correlated with coating solution concentration. Treatments achieved through 2% polymer solutions improved surface hydrophilicity without affecting average pore diameter, tensile modulus, suture retention strength or cell proliferation. Improvements attained through 2% treatment dictated subsequent, long-term cell studies with human bone-derived mesenchymal stem cells (MSCs). The PNEA-mPh surface led to enhanced cell adhesion and increased construct cell infiltration verses PCL matrix control. Both fibrous scaffolds resulted in a tendon relevant bimodal peaking in expression of the tendon differentiation marker Tenomodulin. In contrast, hybrid PCL/PNEA-mPh constructs achieved superior phenotypic maturity with a significantly greater ratio of Collagen I (Col I) to Collagen III (Col III) expression. These findings indicate that PNEA-mPh functionalization supports in vitro tenogenic differentiation and improves cell interactions over PCL scaffolds relevant to scaffold based supraspinatus augmentation applications. The hybrid PCUPNEA-mPh construct was then placed in a novel animal model for scaffold rotator cuff augmentation. Shoulders harvest at 6 and 12 weeks post surgery indicated that scaffold augmentation resulted in morphology similar to suture repair based on hematoxylin and eosin (H&E), Col I: Col III semiquantitation and birefringence. In contrast, application of MSCs with scaffold augmentation resulted in a gradual tendon to bone transmission at the insertion and oriented fibers and cells in the tendon body resembling that of intact supraspinatus tendon. These qualitative findings were also confirmed by Col I:Col III and birefringence assessment. The improved morphology translated into greater structural and mechanical properties over repair and scaffold alone augmented tendons. However, only traces of donor cells were found at 6 weeks and none at 12 weeks post surgery. These findings suggested that the hybrid PCL/PNEA-mPh served as a successful cell delivery system in tendon augmentation, improving healing histologically and biomechanically through paracrine means.