Development of Nanofiber Scaffolds with Controllable Structure and Mineral Content for Tendon-to-Bone Repair

Rotator cuff tears are common and lead to significant pain and disability. Effective repair of torn rotator cuff tendons requires healing of tendon to bone. Unfortunately, healing does not reproduce the structural and compositional features of the natural tendon-to-bone bone attachment that are necessary for effective load transfer, and surgical repairs often rupture. Recent efforts for improving tendon-to-bone healing have focused on tissue engineering approaches. Scaffolds, cells, and/or growth factors are implanted at the repair site to guide the healing process and improve outcomes. To that end, a polymer-mineral tissue engineered scaffold was developed for this thesis which mimics two of the primary features of the tendon-to-bone insertion: aligned nanofibers and hydroxyapatite mineral crystals. The nanofibrous component was created by electrospinning poly lactic-co-glycolic acid to create non-woven mats. The bone-like mineral was then deposited onto the nanofibers using mineralizing solutions. The structure (alignment and crimp microstructure) and composition (mineral content and morphology) of the scaffolds were modulated to understand their influence on scaffold mechanics. Experimental and modeling results demonstrated that: (1) the orientation distribution of the nanofibers was a major determinant of modulus, strength, and anisotropy, (2) crimp microstructure was a major determinant of low strain non-linear mechanical behavior, (3) mineral content positively correlated with modulus and strength and negatively correlated with toughness, (4) mineral morphology was a significant determinant of its stiffening effect, and (5) scaffold-level stiffening by mineral was due to mineral cross-bridges between nanofibers, not due to stiffening of individual nanofibers. Scaffolds were tested in a rotator cuff tendon-to-bone animal model in an effort to improve healing, but were found to be ineffective; the scar-mediated wound healing response dominated over any effects from the scaffold. In summary, a number of mechanisms driving nanofiber mechanics were defined, but further study is needed to effectively apply these scaffolds in the setting of tendon-to-bone repair