Biomimetic and Biphasic Nanocomposite Scaffold with Growth Factor-Encapsulated Nanospheres for Repairing Osteochondral Defects

Biomimetic and Biphasic Nanocomposite Scaffold with Growth Factor-Encapsulated Nanospheres for Repairing Osteochondral Defects

Nathan J. Castro¹, Christopher O'Brien², Lijie Grace Zhang¹

¹Department of Mechanical and Aerospace Engineering

²Department of Electrical and Computer Engineering

The George Washington University, Washington, DC 20052

Email addresses:

Nathan J. Castro: njcastro@gwmail.gwu.edu

Christopher O'Brien: cobrien2@gwmail.gwu.edu

Lijie Grace Zhang: lgzhang@gwu.edu

Abstract: Over 25 million people in the United States alone are afflicted with osteoarthritis or some form of degenerative joint disease. People with this disease experience reduced joint mobility and severe pain due to the gradual loss or traumatic injury to the articular cartilage and subchondral bone which is collectively known as osteochondral tissue. Current treatment methods used to address these defects including autografts, allografts, and mosaicplasties contain their own inherent limitations.  Donor site morbidity, infection, poor tissue integration, and neovascularization continue to prevent the clinical success of traditional methods. Extensive research employing tissue engineering approaches have focused on regenerating both tissues independently with good results.  Due to the complex nature of the osteochondral site both, in composition and mechanical properties, single-material constructs lack the dynamic range necessary to address such distinctly different tissues. Therefore, this work aims at fabricating a biphasic and biomimetic nanostructured construct for osteochondral tissue regeneration. Highly porous poly(caprolactone) (PCL) with bone morphogenetic protein-2 (BMP-2)-encapsulated poly(dioxanone) (PDO) nanospheres as well as nanocrystalline hydroxyapatite is fabricated via porogen-leaching through the combination of water soluble poly(ethylene glycol) diacrylate (PEG-DA) and sodium chloride salt particles, serving as the bone layer of the biphasic scaffold. The use of a co-porogen system has been shown to provide greater control over pore size and architecture. The cartilage layer is composed of PEG-DA with transforming growth factor-β1 (TGF-β1)-encapsulated PLGA nanospheres and is cast on the porous PCL bone layer then cured under ultraviolet (UV) radiation physically joining the two layers by crosslinking of infiltrated PEG-DA. In this manner, a biomimetic nano osteochondral scaffold with sustained chondrogenic and osteogenic growth factor distributions is created. Human bone marrow derived mesenchymal stem cells will be seeded onto each layer and evaluated for directed osteogenic and chondrogenic differentiation in vitro. We expect that sustained growth factor release in combination with a more biomimetic biphasic nanostructured construct will yield a more clinically relevant tissue-engineered construct for improved osteochondral regeneration.