TY - JOUR
T1 - Hypoxic-Mediated Oxidative Stress Condition and Hydroxyapatite-Inducing Osteogenic Differentiation of Human Mesenchymal Stem Cells
T2 - A Mathematical Modeling Study
AU - Cui, Yan Chao
AU - Qiu, Yu Sheng
AU - Wu, Qiong
AU - Bu, Gang
AU - Teh, Seoh Wei
AU - He, Guo Zhong
AU - Mok, Pooi Ling
AU - Samrot, Antony V.
AU - Mariappan, Rajan
AU - Higuchi, Akon
AU - Arulselvan, Palanisamy
AU - Rampal, Sanjiv Rampal Lekhraj
AU - Muthuvenkatachalam, Bala Sundaram
AU - Swamy, K. B.
AU - Sun, Zhong
AU - Ang, Kok Pian
AU - Then, Kong Yong
AU - Kumar, S. Suresh
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Avascular necrosis (AVN) of the bones remains a major clinical challenge. Fractures in the talus, the scaphoid, and the neck of the femur are especially challenging to heal due to the low blood vessel network and the lack of collateral blood supply. These fractures are associated with high rates of nonunion and increased infections that require repeated operations. Conventional treatments by autografting or allografting bone replacement and synthetic bone implants have limitations, including the invasiveness of operative procedures, tissue supply insufficiency, and the risk of host rejection. The advancement in tissue engineering has revealed the potential of stem cells as restorative agents for bone injuries. The administration of mesenchymal stem cells (MSCs) into the talus, the scaphoid, and the neck of the femur could produce enhanced osteogenesis via the manipulation of MSC culture conditions. In this study, we used hydroxyapatite as the nanomaterial, and hypoxic milieu to enhance MSC differentiation capacity into the osteogenic lineage, allowing for more rapid and efficient bone cell replacement treatment. Our results demonstrate 1% oxygen and 12.5 μg/mL of hydroxyapatite (HAP) as the optimal conditions to incorporate the osteogenic medium for the osteogenic induction of MSCs. We also established a proof of concept that the addition of HAP and hypoxic conditions could augment the osteoinductive capacity of MSCs. We also developed an accurate mathematical model to support future bone cell replacement therapy.
AB - Avascular necrosis (AVN) of the bones remains a major clinical challenge. Fractures in the talus, the scaphoid, and the neck of the femur are especially challenging to heal due to the low blood vessel network and the lack of collateral blood supply. These fractures are associated with high rates of nonunion and increased infections that require repeated operations. Conventional treatments by autografting or allografting bone replacement and synthetic bone implants have limitations, including the invasiveness of operative procedures, tissue supply insufficiency, and the risk of host rejection. The advancement in tissue engineering has revealed the potential of stem cells as restorative agents for bone injuries. The administration of mesenchymal stem cells (MSCs) into the talus, the scaphoid, and the neck of the femur could produce enhanced osteogenesis via the manipulation of MSC culture conditions. In this study, we used hydroxyapatite as the nanomaterial, and hypoxic milieu to enhance MSC differentiation capacity into the osteogenic lineage, allowing for more rapid and efficient bone cell replacement treatment. Our results demonstrate 1% oxygen and 12.5 μg/mL of hydroxyapatite (HAP) as the optimal conditions to incorporate the osteogenic medium for the osteogenic induction of MSCs. We also established a proof of concept that the addition of HAP and hypoxic conditions could augment the osteoinductive capacity of MSCs. We also developed an accurate mathematical model to support future bone cell replacement therapy.
UR - http://www.scopus.com/inward/record.url?scp=85096154378&partnerID=8YFLogxK
U2 - 10.1166/jbn.2020.2939
DO - 10.1166/jbn.2020.2939
M3 - 期刊論文
C2 - 33187586
AN - SCOPUS:85096154378
SN - 1550-7033
VL - 16
SP - 910
EP - 921
JO - Journal of biomedical nanotechnology
JF - Journal of biomedical nanotechnology
IS - 6
ER -