Nano Biomedicine

Ectopic Bone Formation in Muscles Using Injectable Bone-forming Material Consisting of Cross-linked Hyaluronic Acid, Bone Morphogenetic Protein, and Nano-hydroxyapatite

Koji IKEDA1, Shiho SUGAWARA1, Masayuki TAIRA2, Hirotaka SATO3, Wataru HATAKEYAMA1, Hidemichi KIHARA1, and Hisatomo KONDO1

1Department of Prosthodontics and Oral Implantology, Iwate Medical University
School of Dentistry, Morioka, Iwate, Japan
2Department of Biomedical Engineering, Iwate Medical University,
3Division of Anatomical and Cellular Pathology, Department of Pathology,
Iwate Medical University, Shiwa-gun, Iwate, Japan

Nano Biomed 2019; 11(1): 11-20, (June 30, Nano Biomedicine)

To accelerate bone formation, we prepared an injectable bone-inducing sol-gel material. Bone morphogenetic protein (BMP) was incorporated into a cross-linkable hyaluronic acid (cHLA) sol with ?SH functional groups with and without nano-hydroxyapatite (nHAP). The test cHLA/BMP/nHAP and control cHLA/BMP sols were injected into the back subcutaneous and thigh intra-muscular tissues of 10-week-old male mice (n=10 each), and allowed to gel for 20 min. After feeding for 8 weeks, calcification at the injection sites was evaluated by micro-computed tomography (CT) and histological examination. CT revealed calcification at the sites of test cHLA/BMP/nHAP sol-gel injection in 80-90% of the mice, while control cHLA/BMP sol-gel could not induce any calcification. Histological observations clarified that new bone formed in the calcification zones at both sites by endochondral ossification. It was thought that nHAP functioned as a carrier that retains and slowly release osteo-inductive BMP. The cHLA/BMP/nHAP sol-gel has potential as an injection-type osteo-inductive biomaterial.

Key words: cross-linked hyaluronic acid, bone morphogenetic protein, nano-hydroxyapatite, endochondral ossification, injection-type bone-forming material

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