Repair of Cranial Bone Defects Using rhBMP2 and Submicron Particle of Biphasic Calcium Phosphate Ceramics with Through-Hole.
Recently a submicron particle of biphasic calcium phosphate ceramic (BCP) with through-hole (donut-shaped BCP (d-BCP)) was developed for improving the osteoconductivity. This study was performed to examine the usefulness of d-BCP for the delivery of osteoinductive rhBMP2 and the effectiveness on cranial bone regeneration. The d-BCP was soaked in rhBMP2 solution and then freeze-dried. Scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), and Raman spectroscopy analyses confirmed that rhBMP2 was well delivered onto the d-BCP surface and the through-hole. The bioactivity of the rhBMP2/d-BCP composite was validated in MC3T3-E1 cells as an in vitro model and in critical-sized cranial defects in C57BL/6 mice. When freeze-dried d-BCPs with rhBMP2 were placed in transwell inserts and suspended above MC3T3-E1, alkaline phosphatase activity and osteoblast-specific gene expression were increased compared to non-rhBMP2-containing d-BCPs. For evaluating in vivo effectiveness, freeze-dried d-BCPs with or without rhBMP2 were implanted into critical-sized cranial defects. Microcomputed tomography and histologic analysis showed that rhBMP2-containing d-BCPs significantly enhanced cranial bone regeneration compared to non-rhBMP2-containing control. These results suggest that a combination of d-BCP and rhBMP2 can accelerate bone regeneration, and this could be used to develop therapeutic strategies in hard tissue healing.
Research Center for Biomineralization Disorders and Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea.
Byung-Chul
BC
Jeong
Research Center for Biomineralization Disorders and Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea.
Hyuck
H
Choi
Research Center for Biomineralization Disorders and Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea.
Sung-Woong
SW
Hur
Research Center for Biomineralization Disorders and Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea.
Jung-Woo
JW
Kim
Research Center for Biomineralization Disorders and Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea.
Sin-Hye
SH
Oh
RIS Foundation for Advanced Biomaterials, Chonnam National University, Gwangju 500-757, Republic of Korea.
Hyun-Seung
HS
Kim
Center for Biomaterials, Korea Institute of Science & Technology, Seoul 130-650, Republic of Korea.
Soo-Chang
SC
Song
Department of Orthopedic Surgery, Chonnam National University Medical School and Hospital, Gwangju 501-757, Republic of Korea.
Keun-Bae
KB
Lee
Megagen Implant, Gyeongsan, Gyeongbuk 712-850, Republic of Korea.
Kwang-Bum
KB
Park
Research Center for Biomineralization Disorders and Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea.
Jeong-Tae
JT
Koh
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002516:Ceramics / Q000494:pharmacology*; D006801:Humans; D006882:Hydroxyapatites / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D012886:Skull / Q000293:injuries*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D006882:Hydroxyapatites; D011994:Recombinant Proteins; C074950:hydroxyapatite-beta tricalcium phosphate