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July 24th, 2012

Microwaving of hydroxyapatite, ZrO2 combo yields promising strong bone graft scaffold

Published on July 24th, 2012 | By: pwray@ceramics.org

Photographs of the mechanically strong and biocompatible hydroxyapatite/t-ZrO2 composite scaffolds prepared by microwave sintering at 1,300°C (a, b), 1,400°C (c, d) and 1500°C (e, f). Credit: Jang et al.; Science and Technology of Advanced Materials.

A group of Korean researchers at Soonchunhyang University who have been working on developing various types of a bone-like scaffolds to help regenerate defective or damaged bone tissue say they have found a fairly uncomplicated mixed-material candidate for use in situations where mechanical strength is a factor but the dimensions are fairly small, such as in fingers and toes. The scaffold is composed of hydroxyapatite and zirconium dioxide. They say the key to making this combination work together—each has separate beneficial characteristics but different coefficients of thermal expansion—is carefully engineering the interface between the two materials and microwave sintering.

Sample of electrospun artificial cancellous-type scaffold. Credit: Kim and Lee; Sci. Technol. Adv. Mater

The group, led by Byong-Taek Lee, has been creating a variety of bone scaffold structures for several years. For example, in 2011, they reported on the clever use of electrospinning to engineer a candidate for artificial cancellous bone, a spongy, soft and weak type of bone tissue found, for example, at the expanded heads of long bones and in the interior of vertebrae.

In contrast to cancellous bone, “compact” or cortical bone is harder, denser and stiffer and provides more structural support for organs and joints and, ultimately, the whole body. This time Lee’s group focused on a substitute for this tougher bone for use in bone graft applications.

Bone grafts have become fairly common in dental reconstruction efforts (to build support for dental implants) and are also used in complicated bone fractures and situations where small amounts of bone are missing or have necessarily been removed. Generally speaking, the graft serves as a temporary support that is gradually replaced by the host’s bone tissue.

Currently, the most widely used materials for bone grafts are tissues taken from elsewhere on the individual or from a cadaver. However, there are drawbacks to both of these sources, and the biomedical materials community in recent years has been active in developing alternative materials and scaffolds for grafting. The search is on among many groups looking for the “ideal” artificial graft materials and several tests have been made using scaffolds of hydroxyapatite, bioactive glass and other ceramic materials.

It is not clear whether there will ever be a single ideal graft material, especially if the composition can be customized based for a specific site. However, at a minimum, any substitute material will have to be fairly light and strong, will have to be porous to allow cell growth and fluid penetration, and will have to encourage bone cell growth (not to mention growth of vascular and neural tissues).

As mentioned above, this recent work in Korea has to do with combining two well known materials, hydroxyapatite and ZrO2. A news release from the National Institute for Materials Science notes that, “While hydroxyapatite encourages bone cell ingrowth, when it is porous like natural bone, it is mechanically weak. The second material, zirconium dioxide, is stronger but cells do not grow on it.”

The question they faced was how to create a scaffold from these very different materials (with normally incompatible coefficients of thermal expansion) without cracking and damaging the structure during the sintering process. In their paper published in the journal Science and Technology of Advanced Materials, “Microwave sintering and in vitro study of defect-free stable porous multilayered HAp-ZrO2 artificial bone scaffold” (doi:10.1088/1468-6996/13/3/035009), the researchers say their goal was “to fabricate a bone preform that can be strong enough to maintain a reasonable load during the natural healing period, and at the same time offers extensive porous space for the bone regeneration to take place throughout the whole scaffold.”

The solution they discovered is to carefully build up hydroxyapatite on the exterior of a ZrO2 core, using a gradient zone between the two, and then sinter using a microwave oven instead of a conventional furnace. In particular, they credit the gradient region with resolving the potential thermal expansion problems.

In their paper, the researchers say the microwave sintering “ensures sufficient sintering within a short time… In this method, the heating rate is relatively high and the dwelling time is significantly shortened, which hinders undesired reactions and, hence, preserves the biocompatibility of the intended materials.

After creating test structures and confirming their strength and porosity, the team seeded the composite with cells and found that they indeed grew successfully, divided as hoped and after several days covered the entire surface. They also found that the cells completely filled the pores and penetrated the ceramic structures.

There is no word about what the group’s next steps are.

I would like to note that the topic of bone repairs and creating scaffolds for tissue regeneration will be thoroughly covered at ACerS’ upcoming Innovations in Biomedical Materials 2012 conference scheduled for Sept. 10-13 in Raleigh, N.C. The tracks in this meeting include

• Uses of Bioactive Glass in New Treatments

• Three-Dimensional Scaffolds for Tissue Regeneration

• Blood Vessel and Nerve Guide

• Malleable Bone Void Fillers (Bone Cements or Putty) and

• Composites.

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