TY - JOUR
T1 - Isotope Microscopic Observation of Osteogenesis Process Forming Robust Bonding of Double Network Hydrogel to Bone
AU - Nonoyama, Takayuki
AU - Wang, Lei
AU - Tsuda, Masumi
AU - Suzuki, Yuki
AU - Kiyama, Ryuji
AU - Yasuda, Kazunori
AU - Tanaka, Shinya
AU - Nagata, Kousuke
AU - Fujita, Ryosuke
AU - Sakamoto, Naoya
AU - Kawasaki, Noriyuki
AU - Yurimoto, Hisayoshi
AU - Gong, Jian Ping
N1 - Funding Information:
All animal experiments were given ethical approval by the Institute of Animal Experimentation at Hokkaido University. This research was financially supported by JSPS KAKENHI (Grant Nos. 17H06144 and JP17H06376). The authors thank the Open Facility, Global Facility Center of Hokkaido University, for isotope microscopic measurements. The authors thank Prof. Kuniharu Ijiro (Hokkaido University) for precious suggestion on the work. The authors also thank Dr. Masanori Kikuchi (National Institute for Materials Science), Prof. Chikara Ohtsuki (Nagoya University), and Prof. Kunio Ishikawa (Kyusyu University) for discussions on the HAp reutilization.
Funding Information:
All animal experiments were given ethical approval by the Institute of Animal Experimentation at Hokkaido University. This research was financially supported by JSPS KAKENHI (Grant Nos. 17H06144 and JP17H06376). The authors thank the Open Facility, Global Facility Center of Hokkaido University, for isotope microscopic measurements. The authors thank Prof. Kuniharu Ijiro (Hokkaido University) for precious suggestion on the work. The authors also thank Dr. Masanori Kikuchi (National Institute for Materials Science), Prof. Chikara Ohtsuki (Nagoya University), and Prof. Kunio Ishikawa (Kyusyu University) for discussions on the HAp reutilization.
Publisher Copyright:
© 2020 Wiley-VCH GmbH
PY - 2021/2/3
Y1 - 2021/2/3
N2 - Tough double network (DN) hydrogels are promising substitutes of soft supporting tissues such as cartilage and ligaments. For such applications, it is indispensable to robustly fix the hydrogels to bones with medically feasible methods. Recently, robustly bonding the DN hydrogels to defected bones of rabbits in vivo has been proved successful. The low crystalline hydroxyapatite (HAp) of calcium-phosphate-hydroxide salt coated on the surface layer of the DN hydrogels induced spontaneous osteogenesis penetrating into the semi-permeable hydrogels to form a gel/bone composite layer. In this work, the 44Ca isotope-doped HAp/DN hydrogel is implanted in a defect of rabbit femoral bone and the dynamic osteogenesis process at the gel/bone interface is analyzed by tracing the calcium isotope ratio using isotope microscopy. The synthetic HAp hybridized on the surface layer of DN gel dissolves rapidly in the first two weeks by inflammation, and then the immature bone with a gradient structure starts to form in the gel region, reutilizing the dissolved Ca ions. These results reveal, for the first time, that synthetic HAp is reutilized for osteogenesis. These facts help to understand the lifetime of bone absorbable materials and to elucidate the mechanism of spontaneous, non-toxic, but strong fixation of hydrogels to bones.
AB - Tough double network (DN) hydrogels are promising substitutes of soft supporting tissues such as cartilage and ligaments. For such applications, it is indispensable to robustly fix the hydrogels to bones with medically feasible methods. Recently, robustly bonding the DN hydrogels to defected bones of rabbits in vivo has been proved successful. The low crystalline hydroxyapatite (HAp) of calcium-phosphate-hydroxide salt coated on the surface layer of the DN hydrogels induced spontaneous osteogenesis penetrating into the semi-permeable hydrogels to form a gel/bone composite layer. In this work, the 44Ca isotope-doped HAp/DN hydrogel is implanted in a defect of rabbit femoral bone and the dynamic osteogenesis process at the gel/bone interface is analyzed by tracing the calcium isotope ratio using isotope microscopy. The synthetic HAp hybridized on the surface layer of DN gel dissolves rapidly in the first two weeks by inflammation, and then the immature bone with a gradient structure starts to form in the gel region, reutilizing the dissolved Ca ions. These results reveal, for the first time, that synthetic HAp is reutilized for osteogenesis. These facts help to understand the lifetime of bone absorbable materials and to elucidate the mechanism of spontaneous, non-toxic, but strong fixation of hydrogels to bones.
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U2 - 10.1002/adhm.202001731
DO - 10.1002/adhm.202001731
M3 - Article
C2 - 33191665
AN - SCOPUS:85096696363
VL - 10
JO - Advanced healthcare materials
JF - Advanced healthcare materials
SN - 2192-2640
IS - 3
M1 - 2001731
ER -