TY - JOUR
T1 - Conjugation of bone grafts with NO-delivery dinitrosyl iron complexes promotes synergistic osteogenesis and angiogenesis in rat calvaria bone defects
AU - Chang, Shih Hao
AU - Hsiao, Hui Yi
AU - Chen, Yi Hong
AU - Cheng, Ming Huei
AU - Liu, Jia Wei
AU - Huang, Hsiao Jo
AU - Chou, Yu Ting
AU - Amer, Tarik Abdelkareem Mostafa
AU - Vijayaraghavan, Priya
AU - Palanisamy, Sathyadevi
AU - Wang, Yun Ming
AU - Lu, Tsai Te
N1 - Publisher Copyright:
© 2023 The Royal Society of Chemistry
PY - 2023/7/18
Y1 - 2023/7/18
N2 - Craniofacial/jawbone deformities remain a significant clinical challenge in restoring facial/dental functions and esthetics. Despite the reported therapeutics for clinical bone tissue regeneration, the bioavailability issue of autografts and limited regeneration efficacy of xenografts/synthetic bone substitutes, however, inspire continued efforts towards functional conjugation and improvement of bioactive bone graft materials. Regarding the potential of nitric oxide (NO) in tissue engineering, herein, functional conjugation of NO-delivery dinitrosyl iron complex (DNIC) and osteoconductive bone graft materials was performed to optimize the spatiotemporal control over the delivery of NO and to activate synergistic osteogenesis and angiogenesis in rat calvaria bone defects. Among three types of biomimetic DNICs, [Fe2(μ-SCH2CH2COOH)2(NO)4] (DNIC-COOH) features a steady kinetics for cellular uptake by MC3T3-E1 osteoblast cells followed by intracellular assembly of protein-bound DNICs and release of NO. This steady kinetics for intracellular delivery of NO by DNIC-COOH rationalizes its biocompatibility and wide-spectrum cell proliferation effects on MC3T3-E1 osteoblast cells and human umbilical vein endothelial cells (HUVECs). Moreover, the bridging [SCH2CH2COOH]− thiolate ligands in DNIC-COOH facilitate its chemisorption to deproteinized bovine bone mineral (DBBM) and physisorption onto TCP (β-tricalcium phosphate), respectively, which provides a mechanism to control the kinetics for the local release of loaded DNIC-COOH. Using rats with calvaria bone defects as an in vivo model, DNIC-DBBM/DNIC-TCP promotes the osteogenic and angiogenic activity ascribed to functional conjugation of osteoconductive bone graft materials and NO-delivery DNIC-COOH. Of importance, the therapeutic efficacy of DNIC-DBBM/DNIC-TCP on enhanced compact bone formation after treatment for 4 and 12 weeks supports the potential for clinical application to regenerative medicine.
AB - Craniofacial/jawbone deformities remain a significant clinical challenge in restoring facial/dental functions and esthetics. Despite the reported therapeutics for clinical bone tissue regeneration, the bioavailability issue of autografts and limited regeneration efficacy of xenografts/synthetic bone substitutes, however, inspire continued efforts towards functional conjugation and improvement of bioactive bone graft materials. Regarding the potential of nitric oxide (NO) in tissue engineering, herein, functional conjugation of NO-delivery dinitrosyl iron complex (DNIC) and osteoconductive bone graft materials was performed to optimize the spatiotemporal control over the delivery of NO and to activate synergistic osteogenesis and angiogenesis in rat calvaria bone defects. Among three types of biomimetic DNICs, [Fe2(μ-SCH2CH2COOH)2(NO)4] (DNIC-COOH) features a steady kinetics for cellular uptake by MC3T3-E1 osteoblast cells followed by intracellular assembly of protein-bound DNICs and release of NO. This steady kinetics for intracellular delivery of NO by DNIC-COOH rationalizes its biocompatibility and wide-spectrum cell proliferation effects on MC3T3-E1 osteoblast cells and human umbilical vein endothelial cells (HUVECs). Moreover, the bridging [SCH2CH2COOH]− thiolate ligands in DNIC-COOH facilitate its chemisorption to deproteinized bovine bone mineral (DBBM) and physisorption onto TCP (β-tricalcium phosphate), respectively, which provides a mechanism to control the kinetics for the local release of loaded DNIC-COOH. Using rats with calvaria bone defects as an in vivo model, DNIC-DBBM/DNIC-TCP promotes the osteogenic and angiogenic activity ascribed to functional conjugation of osteoconductive bone graft materials and NO-delivery DNIC-COOH. Of importance, the therapeutic efficacy of DNIC-DBBM/DNIC-TCP on enhanced compact bone formation after treatment for 4 and 12 weeks supports the potential for clinical application to regenerative medicine.
UR - http://www.scopus.com/inward/record.url?scp=85167521093&partnerID=8YFLogxK
U2 - 10.1039/d3tb00587a
DO - 10.1039/d3tb00587a
M3 - Article
C2 - 37530140
AN - SCOPUS:85167521093
SN - 2050-750X
VL - 11
SP - 8007
EP - 8019
JO - Journal of Materials Chemistry B
JF - Journal of Materials Chemistry B
IS - 33
ER -