Better ways to heal and regenerate bones using microcomputed tomography imaging

Tissue engineers can choose from a wide range of living cells, biomaterials and proteins to repair a bone defect. But finding the optimum combination requires improved methods for tracking the healing process.

New Georgia Tech research points to better ways to heal and regenerate bones using microcomputed tomography (micro-CT) imaging — a process 1 million times more detailed than a traditional CT scan. The new micro-CT scan technique simultaneously looks at both vascularization (the process by which blood vessels invade body tissues during repair) and mineralization (the process by which mineral crystals form to harden regenerating bone) by collecting three-dimensional images in vitro and in vivo.

Georgia Tech researchers used the new technique to help develop bone graft substitutes that combine the availability and structural integrity of bone allografts, or bone grafts taken from a human donor, with the better healing properties of bone autografts, or bone grafts taken from the patient.

Unlike a traditional x-ray that only shows the presence of bone in two dimensions, the new micro-CT technique provides high-resolution 3-D images of vascularization and mineralization during bone repair. This approach allows tissue engineers to optimize the design of implants.

The findings of the project, headed by Dr. Robert Guldberg, a research director at the Georgia Tech/Emory Center for the Engineering of Living Tissues and an associate professor in Georgia Tech's School of Mechanical Engineering, will be presented Feb. 20 at the annual meeting of the American Association for the Advancement of Science (AAAS).

"We're applying 3-D imaging techniques to quantify vascularization and mineralization in order to evaluate which of these tissue engineering approaches is going to be able to best and most quickly restore bone function," Guldberg said. "We've always known that vascularization is very important to bone repair, but we've never really had a good method to measure the process."

Guldberg's team has used micro-CT imaging to study fracture healing and repair of large bone defects that can result from the removal of bone tumors or crushing injuries. Large bone defects are typically repaired with allografts because large structural pieces are available from human donors.

But allografts are processed to avoid transmitting any diseases from the donor to the patient, leaving the bone sterile but dead. Allografts therefore lack living cells that could help the implants better integrate with existing bone. Consequently, they don't heal as well as autografts and can re-break in up to 30 percent of patients within a year. Live autograft bone integrates much better, but large amounts of bone are needed to repair a site. They are often too large to remove elsewhere in the patient's body and cause substantial additional pain.

Georgia Tech's micro-CT imaging facility has been used to study tissue engineering approaches to enhance or replace the use of bone grafts clinically. Guldberg and his collaborators at the University of Rochester, for example, have explored various strategies to revitalize dead allograft bone. Wrapping allografts with biomaterials containing living marrow cells or delivering bioactive genes has resulted in significantly accelerated repair and integration of allograft implants.

While a traditional bone scan can give a doctor some idea of a bone's density, a micro-CT scan that provides high resolution 3-D data on vascularization and mineralization can provide much more detailed information about the bone's structure and blood flow. Although not yet available clinically, these techniques give researchers an unprecedented depth of data on how a bone implant is integrating into the body.

In addition to studying bone regeneration, the ability to look at detailed 3-D images of vascular networks can shed light on research into vascular injuries, disc degeneration in the back and help detect tumors early by pinpointing areas of increased vascularization (which often indicate tumor growth).