Abstract

The effect of the geometric structure of artificial biomaterials on skull regeneration remains unclear. In a previous study, we succeeded in developing honeycomb β-tricalcium phosphate (β-TCP), which has through-and-through holes and is able to provide the optimum bone microenvironment for bone tissue regeneration. We demonstrated that β-TCP with 300-μm hole diameters induced vigorous bone formation. In the present study, we investigated how differences in hole directions of honeycomb β-TCP (horizontal or vertical holes) influence bone tissue regeneration in skull defects. Honeycomb β-TCP with vertical and horizontal holes was loaded with BMP-2 using Matrigel and Collagen gel as carriers, and transplanted into skull bone defect model rats. The results showed that in each four groups (Collagen alone group, Matrigel alone group, Collagen + BMP group and Matrigel + BMP-2), vigorous bone formation was observed on the vertical β-TCP compared with horizontal β-TCP. The osteogenic area was larger in the Matrigel groups (with and without BMP-2) than in the Collagen group (with and without BMP-2) in both vertical β-TCP and horizontal β-TCP. However, when BMP-2 was added, the bone formation area was not significantly different between the Collagen group and the Matrigel group in the vertical β-TCP. Histological finding showed that, in vertical honeycomb β-TCP, new bone formation extended to the upper part of the holes and was observed from the dura side to the periosteum side as added to the inner walls of the holes. Therefore, we can control efficient bone formation by creating a bone microenvironment provided by vertical honeycomb β-TCP. Vertical honeycomb β-TCP has the potential to be an excellent biomaterial for bone tissue regeneration in skull defects and is expected to have clinical applications.

Highlights

  • The ability of the calvaria to regeneration is low, and when a bone defect occurs due to trauma or surgical craniotomy and craniectomy, it is difficult for the skull defect to completely heal even in young people

  • Bone tissue formation was found only in the lower layer adjacent to the dura, and no bone tissue was found in the periosteal side holes. (D) Low-magnification image of vertical β-tricalcium phosphate (β-tricalcium phosphate (TCP))

  • In the Matrigel-loaded horizontal honeycomb β-TCP, new bone formation extended to the upper part of the holes and was observed from the dura side to the periosteum side as added to the inner walls of the holes; the bone formation ability was weak compared to the vertical honeycomb β-TCP

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Summary

Introduction

The ability of the calvaria to regeneration is low, and when a bone defect occurs due to trauma or surgical craniotomy and craniectomy, it is difficult for the skull defect to completely heal even in young people. Cranial bone reconstruction requires strength and biocompatibility, autologous bone transplantation is clinically the most common method. Autologous bone transplantation is highly invasive and burdens the patient [1,2]. Materials 2020, 13, 4761 such as hydroxyapatite has recently become used for skull defects. These non-resorbable artificial bones block blood flow and the interaction between the artificial bone and adjacent tissues, causing fragility and distortion of surrounding tissues and susceptibility to infection [3,4,5]. The usefulness of absorbable ceramics with high biocompatibility such as tricalcium phosphate (TCP) has been shown to be effective for bone tissue reconstruction due to high biocompatibility and high bone tissue induction. TCP is already widely clinically applied [5,6,7,8,9,10]

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