Isotope Microscopic Observation of Osteogenesis Process Forming Robust Bonding of Double Network Hydrogel to Bone,Advanced Healthcare Materials

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Isotope Microscopic Observation of Osteogenesis Process Forming Robust Bonding of Double Network Hydrogel to Bone
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-11-16 , DOI: 10.1002/adhm.202001731
Takayuki Nonoyama _{1,

2} , Lei Wang _{2,

3} , Masumi Tsuda _{2,

3,

4} , Yuki Suzuki ₅ , Ryuji Kiyama ₅ , Kazunori Yasuda _{1,

2} , Shinya Tanaka _{2,

3,

4} , Kousuke Nagata ₆ , Ryosuke Fujita _{7,

8} , Naoya Sakamoto ₇ , Noriyuki Kawasaki ₆ , Hisayoshi Yurimoto ₆ , Jian Ping Gong _{1,

2,

4}

Affiliation

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.

中文翻译：

成骨过程形成双网状水凝胶与骨骼的牢固结合的同位素显微镜观察

坚韧的双网络（DN）水凝胶是软支撑组织（如软骨和韧带）的有希望的替代品。对于这样的应用，通过医学上可行的方法将水凝胶牢固地固定在骨骼上是必不可少的。最近，已经证明将DN水凝胶牢固地结合到兔的缺损骨骼上是成功的。DN水凝胶表面层上包覆的磷酸氢钙氢氧化钙盐的低结晶羟基磷灰石（HAp）导致自发性成骨作用渗透到半透性水凝胶中，形成凝胶/骨复合层。在这项工作中，⁴⁴将Ca同位素掺杂的HAp / DN水凝胶植入兔股骨缺损中，并使用同位素显微镜通过追踪钙同位素比来分析凝胶/骨界面的动态成骨过程。DN凝胶表层上杂交的合成HAp在头两周因炎症迅速溶解，然后在凝胶区域开始形成具有梯度结构的未成熟骨骼，从而重新利用溶解的Ca离子。这些结果首次揭示了合成的HAp被重新用于成骨。这些事实有助于了解可吸收骨骼的材料的寿命，并阐明水凝胶自发，无毒但牢固固定在骨骼上的机制。

更新日期：2020-11-16

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