The Need for Bone Substitutes

The importance of orthopedic substitutes and healing therapies is underscored by the following news story:

Many of these cases require bone graft substitutes to repair the injury or defect. There are currently on the order of 500,000 bone grafts performed annually in the U.S. For example, there were an estimated 220,000 spinal fusion cases performed in 1998 requiring bone grafts to secure areas of the spine affected by deformity, trauma, tumors, or degenerative disc disease as depicted in Figure 1a. And, there are approximately 170,000 fractures in the United States that fail to heal each year and are diagnosed as ‘non-unions’ (i.e., fractures that have failed to heal within nine months) that require some form of bone substitute to repair the fracture; Figure 1b shows an example of a non-union of the femur as a result of a motorcycle accident.

  a. Collapsed disc.                  b. Non-Union                    
Figure 1. Example cases requiring bone substitutes to surgically repair damaged tissue.

Current Therapies

To address the need for bone substitutes, current clinical therapies include:

1. Autografting, which represents about 58% of the current bone substitutes, involves harvesting a bone from one location in the patient’s body and transplanting it into another part of the same patient. Using autologous grafts, when available, typically produces the best clinical results; successful clinical outcomes can exceed 80%. Auotgrafting is thus considered the ‘gold standard.’ An example of one the most commonly performed bone autografting procedures is for use in spinal fusion. In a fusion procedure, bone graft from the patient's hip is implanted in disc spaces between spinal vertebrae or along the back of the spine (Figure 2). The grafted bone fuses the vertebrae together over several months. The benefit from transplanting an autogenous tissue is obvious: immunogenicity is not an issue. Autografting, however, has several associated problems including the additional surgical costs for the harvesting procedure, and infection and pain at the harvesting site. For example, harvesting an ileac crest graft (i.e., the protruding bony section of the patient's hip) can cost between $1000 to $9,000/procedure for the harvesting operation and the additional hospital stay. The morbidity at the harvest site can be tremendous with problems such as pain, infection, and blood loss requiring blood transfusion adding the associated risks of transfusion reaction and blood borne infection.

Figure 2. Autografting procedure to repair collapsed disc.

2. Allografting, which represents about %34 of the current bone substitutes, involves harvesting and processing bone from a cadaver then transplanting it to the patient. Allogenic implants are acellular and are less successful than autografts for reasons attributed to immuogenicity and the absence of viable cells that become osteoblasts. Another disadvantage of allografting is concern with transmitted disease

3. Man-made materials, including metals, plastics, and ceramics represent approximately %8 of bone substitutes. These materials, however, are subject to fatigue, fracture, toxicity, and wear, and do not remodel with time (i.e., a metal bone implant cannot grow with the patient and it cannot change shape in response to the loads placed upon the implant. For all these reasons, there is a real need for alternative, off-the-shelf, bone substitutes and better wound healing therapies. Bone tissue engineering seeks to address this need