TY - JOUR
T1 - Functionalization of PCL-3D electrospun nanofibrous scaffolds for improved BMP2-induced bone formation
AU - Miszuk, Jacob M.
AU - Xu, Tao
AU - Yao, Qingqing
AU - Fang, Fang
AU - Childs, Josh D.
AU - Hong, Zhongkui
AU - Tao, Jianning
AU - Fong, Hao
AU - Sun, Hongli
N1 - Funding Information:
This work was supported by the EPSCoR program of National Science Foundation (Award No.: IIA-1335423) and by the Competitive Research Grant program of South Dakota Board of Regents (Award No.: UP1500172, UP1600205). The authors would like to acknowledge the assistance provided by the Sanford Research Imaging Core and Molecular Pathology Core, which were supported by the COBRE grants of National Institutes of Health (Grant Nos.: P20 GM103620 and P20 GM103548 ). The authors would also thank Dr. Erin B. Harmon for his outstanding technical assistance.
PY - 2018/3
Y1 - 2018/3
N2 - Bone morphogenic protein 2 (BMP2) is a key growth factor for bone regeneration, possessing FDA approval for orthopedic applications. BMP2 is often required in supratherapeutic doses clinically, yielding adverse side effects and substantial treatment costs. Considering the crucial role of materials for BMPs delivery and cell osteogenic differentiation, we devote to engineering an innovative bone-matrix mimicking niche to improve low dose of BMP2-induced bone formation. Our previous work describes a novel technique, named thermally induced nanofiber self-agglomeration (TISA), for generating 3D electrospun nanofibrous (NF) polycaprolactone (PCL) scaffolds. TISA process could readily blend PCL with PLA, leading to increased osteogenic capabilities in vitro, however, these bio-inert synthetic polymers produced limited BMP2-induced bone formation in vivo. We therefore hypothesize that functionalization of NF 3D PCL scaffolds with bone-like hydroxyapatite (HA) and BMP2 signaling activator phenamil will provide a favorable osteogenic niche for bone formation at low doses of BMP2. Compared to PCL-3D scaffolds, PCL/HA-3D scaffolds demonstrated synergistically enhanced osteogenic differentiation capabilities of C2C12 cells with phenamil. Importantly, in vivo studies showed that this synergism was able to generate significantly increased new bone in an ectopic mouse model, suggesting that PCL/HA-3D scaffolds act as a favorable synthetic extracellular matrix for bone regeneration.
AB - Bone morphogenic protein 2 (BMP2) is a key growth factor for bone regeneration, possessing FDA approval for orthopedic applications. BMP2 is often required in supratherapeutic doses clinically, yielding adverse side effects and substantial treatment costs. Considering the crucial role of materials for BMPs delivery and cell osteogenic differentiation, we devote to engineering an innovative bone-matrix mimicking niche to improve low dose of BMP2-induced bone formation. Our previous work describes a novel technique, named thermally induced nanofiber self-agglomeration (TISA), for generating 3D electrospun nanofibrous (NF) polycaprolactone (PCL) scaffolds. TISA process could readily blend PCL with PLA, leading to increased osteogenic capabilities in vitro, however, these bio-inert synthetic polymers produced limited BMP2-induced bone formation in vivo. We therefore hypothesize that functionalization of NF 3D PCL scaffolds with bone-like hydroxyapatite (HA) and BMP2 signaling activator phenamil will provide a favorable osteogenic niche for bone formation at low doses of BMP2. Compared to PCL-3D scaffolds, PCL/HA-3D scaffolds demonstrated synergistically enhanced osteogenic differentiation capabilities of C2C12 cells with phenamil. Importantly, in vivo studies showed that this synergism was able to generate significantly increased new bone in an ectopic mouse model, suggesting that PCL/HA-3D scaffolds act as a favorable synthetic extracellular matrix for bone regeneration.
KW - 3D electrospun nanofibrous scaffold
KW - Bone regeneration
KW - Hydroxyapatite functionalization
KW - Osteogenic differentiation
KW - Phenamil
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U2 - 10.1016/j.apmt.2017.12.004
DO - 10.1016/j.apmt.2017.12.004
M3 - Article
C2 - 29577064
AN - SCOPUS:85039077765
VL - 10
SP - 194
EP - 202
JO - Applied Materials Today
JF - Applied Materials Today
SN - 2352-9407
ER -