Date of Completion

12-1-2017

Embargo Period

12-1-2017

Keywords

Osteoarthritis, Cartilage-Bone Interface, Osteochondral, Tissue Regeneration, CD271 Positive Stem Cells, Growth Factors, Hydrogel, Co-Differentiation, Medial Femoral Condyle Defect, In Vivo

Major Advisor

Dr. Syam Nukavarapu

Associate Advisor

Dr. Caroline Dealy

Associate Advisor

Dr. Yusuf Khan

Associate Advisor

Dr. Cato Laurencin

Associate Advisor

Dr. Mei Wei

Field of Study

Biomedical Engineering

Degree

Doctor of Philosophy

Open Access

Campus Access

Abstract

Articular cartilage is an extremely complex and hierarchical tissue whose simplicity acts as its greatest weakness in terms of regeneration. Upon damage, the four major zones of articular cartilage (the superficial, middle, deep and calcified cartilage) are incapable of regenerating properly due to its avascular nature and inactive cell population.

Through this work, a unique scaffold system for cartilage-bone interface regeneration has been proposed and developed. It is hypothesized that only through proper regeneration of the cartilage-bone, osteochondral (OC) region, as unit, will the regeneration of intact cartilage and bone tissue occur. The scaffold system developed consists of a biodegradable gradient scaffold that is later combined with a hyaluronan-based hydrogel to develop an inversely graded matrix scaffold. The ability of the hydrogel portion to support robust chondrogenic differentiation of human mesenchymal stem cells (hMSCs) is shown and later means by which the co-differentiation of both the cartilaginous and bony portions could be supported in vitro was determined. Through the modification of the scaffold to incorporate hydroxyapatite as well as O2 plasma treatment, the scaffold was loaded with osteogenic and chondrogenic growth factors. When these results are applied in vivo, in a rabbit medial femoral condyle defect model, and compared to untreated defects it is concluded that the designed scaffold, containing regions ideal for distal cartilage regeneration as well as proximal bone regeneration seamlessly bound by a gradual transition of the component materials, along with the proper cellular and biochemical cues can in fact support the regeneration of osteochondral-like tissue.

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