Abstract

Osteoinduction in muscles by porous ceramics has been reported to be a real phenomenon. In this study, osteoinduction in connective tissues was found in highly porous hydroxyapatite (HAp) ceramics with large specific surface areas. We have developed the combination method of the partial dissolution-precipitation (PDP) technique involving the stirring-supersonic treatment in 1.7 × 10−2 N HNO3 solution containing Ca2+ and PO43− to improve the surface and the bulk of commercially available synthetic HAp block (82.5% in porosity, 50–300 µm in pore size). The modified HAp was named as a partially dissolved and precipitated HAp (PDP-HAp). The PDP-HAp exhibited the porosities of 85–90%, the macropore sizes of 50–200 µm, and the specific surface areas of 1.0–2.0 m2/g, with microcracks. The aim of this study was to observe bone induction by the PDP-HAp with or without BMP-2 in scalp tissues of four-week-old rats. Young rats were divided into the PDP-HAp alone group and the PDP-HAp/BMP-2 group for a long-term observation. In the PDP-HAp group, bone induction occurred inside the many pores at nine months, and the ratio of induced bone was 12.0%. In the PDP-HAp/BMP-2 group, bone induction occurred in almost all pores at three months, and compact bone was found at nine months. The ratios of induced bone were 77.0% at three months and 86.0% at nine months. We believe that osteoinduction by the PDP-HAp might be different from the process of BMP-loaded HAp-induced bone formation, because the PDP-HAp has osteogenic microporous compartments with partially absorbable HAp crystals. The PDP technique may contribute to create bioceramics with osteoinductive property for bone regenerative medicine.

Highlights

  • Ectopic bone was found in micropores of ceramics in the muscles of large animals [1,2,3,4,5], and the microporosity played an important role in enhancing the osteoinduction of scaffolds [6,7,8,9,10,11,12,13]

  • In vivo implantation of partial dissolution-precipitation (PDP)-HAp used in this study revealed that partially dissolved and precipitated HAp (PDP-HAp) was gradually degraded and was replaced by new bone in the rabbit bone defect model [31]

  • The PDP method contributed to the modification of the originally synthetic HAp as for the microcrack formation inside bulk and the increase of specific surface area by biological

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Summary

Introduction

Mechanism of Osteoinductive Process in Microporosity of Ceramics. Porous calcium phosphate scaffolds with microporosity (pore size smaller than 10 μm) induced ectopic bone formation intramuscularly in several animals [1,2,3,4], without the addition of bone morphogenetic proteins (BMPs) [5]. Ectopic bone was found in micropores of ceramics in the muscles of large animals [1,2,3,4,5], and the microporosity played an important role in enhancing the osteoinduction of scaffolds [6,7,8,9,10,11,12,13]. The exact mechanism of osteoinductive process is still unknown. In vitro study reported that an increase in extracellular Ca2+

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