(155g) 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.