During the last century, there has been a revolution in orthopedics with a shift in emphasis from palliative treatment of infection in bone to interventional treatment of chronic age-related ailments. The evolution of stable metallic fixation devices, and the systematic development of reliable total joint prostheses were critical to this revolution in health care. Two alternative pathways of treatment for patients with chronic bone and joint defects are now possible: (1) transplantation or (2) implantation. Figure 1 shows how approaches to tissue repair have changed and how we think they need to develop.
At present the ''gold standard'' for the clinical repair of large bone defects is the harvesting of the patient's tissue from a donor site and transplanting it to a host site, often maintaining blood supply. This type of tissue graft (an autograft) has limitations; limited availability, morbidity at the donor site, tendency toward resorption, and a compromise in biomechanical properties compared to the host tissue.
A partial solution to some of these limitations is use of transplant tissue from a human donor, a homograft, either as a living transplant (heart, heart-lung, kidney, liver, retina) or from cadavers (freeze-dried bone). Availability, the requirement for lifetime use of immunosuppressant drugs, the concern for viral or prion contamination, ethical, and religious concerns all limit the use of homografts. The first organ transplant (homograft) was carried out in Harvard in 1954. In the United States alone, there are now >80,000 organs needed for transplantation at one time, only a quarter of which will be found. The shortage of donors increases every year.
A third option for tissue replacement is provided by transplants (living or nonliving) from other species called heterografts or xenografts. Nonliving, chemically treated xenografts are routinely used as heart valve replacements (porcine) with ~ 50% survivability after 10 years. Bovine bone grafts are still in use, but concern of transmission of prions (disease transmission) is growing.
The second line of attack in the revolution to replace tissues was the development of manmade materials to interface with living, host tissues (e.g., implants or prostheses made from biomaterials). There are important advantages of implants over transplants, including availability, reproducibility, and reliability. Failure rate of the materials used in most prostheses are very low, at <0.01% (1). As a result, survivability of orthopedic implants such as the Charnley low friction metal-polyethylene total hip replacement is very high up to 15 years (2).
Many implants in use today continue to suffer from problems of interfacial stability with host tissues, biomechanical mismatch of elastic moduli, production of wear debris, and maintenance of a stable blood supply. These problems lead to accelerated wear rates, loosening and fracture of the bone, interface or device that become worse as the patient ages (3). Repair of failed devices, called revision surgery, also becomes more difficult as the patient ages due to decreased quality of bone, reduced mobility, and poorer circulation of blood. In addition, all present day orthopedic implants lack two of the most critical characteristics of living tissues: (1) ability to self-repair; and (2) ability to modify their structure and properties in response to environmental factors such as mechanical load. The consequences of these limitations are profound. All implants have limited lifetimes. Many years of research and development have led to only marginal improvements in the survivability of orthopedic implants for >15years. Ideally, artifical implants or devices should be designed to stimulate and guide cells in the body to regenerate tissues and organs to a healthy and natural state. We need to shift our thinking toward regenerative medicine (Fig. 1) (4).