There
is an increasing need for bone substitutes for reconstructive
orthopedic surgery following removal of bone tumors. Despite the advances
in bone regeneration, the use of autologous mesenchymal stem cells
(MSC) presents a significant challenge, particularly for the treatment
of large bone defects in cancer patients. This study aims at developing
new chemokine-based technology to generate biodegradable scaffolds
that bind pharmacologically active proteins for regeneration/repair
of target injured tissues in patients. Primary MSC were cultured from
the uninvolved bone marrow (BM) of cancer patients and further characterized
for “stemness”. Their ability to differentiate into
an osteogenic lineage was studied in 2D cultures as well as on 3D
macroporous PLGA scaffolds incorporated with biomacromolecules bFGF
and homing factor chemokine stromal-cell derived factor-1 (SDF1).
MSC from the uninvolved BM of cancer patients exhibited properties
similar to that reported for MSC from BM of healthy individuals. Macroporous
PLGA discs were prepared and characterized for pore size, architecture,
functional groups, thermostability, and cytocompatibility by ESEM,
FTIR, DSC, and CCK-8 dye proliferation assay, respectively. It was
observed that the MSC+PLGA+bFGF+SDF1 construct cultured for 14 days
supported significant cell growth, osteo-lineage differentiation with
increased osteocalcin expression, alkaline phosphatase secretion,
calcium mineralization, bone volume, and soluble IL6 compared to unseeded
PLGA and PLGA+MSC, as analyzed by confocal microscopy, biochemistry,
ESEM, microCT imaging, flow cytometry, and EDS. Thus, chemotactic
biomacromolecule SDF1-guided tissue repair/regeneration ability of
MSC from cancer patients opens up the avenues for development of “off-the-shelf”
pharmacologically active construct for optimal repair of the target
injured tissue in postsurgery cancer patients, bone defects, damaged
bladder tissue, and radiation-induced skin/mucosal lesions.