Pretty soon, metal implants and extra glasses of milk won't be the prevailing prescription for broken and defective bones. Tissue engineering technology and advances in polymer science will soon let surgeons repair bones with "living implants" grown from the patient's own marrow cells. "In five to ten years, this biological alternative will make metal implants the exception," predicts Dr. Clemens van Blitterswijk, president and CEO of IsoTis, NV and a specialist in tissue engineering.
He may not be far off the mark, given IsoTis' progress in bone substitution techniques. The company last year kicked off the first clinical trial for use of tissue-engineered bone derived from the patient's own cells. Patients have received these autologous implants in hip revision and jaw augmentation surgeries.
To make tissue-engineered bone, the company starts with marrow harvested from the patient's pelvis or jawbone. This tissue provides osteoprogenitor cells, which the company's scientists seed onto an implantable biomaterial. With the right stimulus in the lab, these marrow cells develop into 'osteoblasts,' or bone-forming cells. "The patient then receives an implant in the form of the biomaterial covered with a living bone matrix," van Blitterswijk explains. Once in the body, the biomaterial degrades over time, and the matrix fills in with natural bone growth as the patient heals.
As much as tissue engineering relies on biotechnology, its success also hinges on a growing slate of biodegradable thermoplastics. With some technical input from the recently completed IsoBone project, a four-year study funded by the European Union, IsoTis has developed several materials that can serve as scaffolds for the bone-forming cells.
The clinical trials, as well as the most immediate commercial prospects, use the bone scaffold to augment existing bone, filling gaps left by defects or by earlier implants that have begun to wear out. IsoTis has come up with two patented material solutions for these surgical spackling jobs, including a thermoplastic. Called Polyactive, this biodegradable copolyesterether has been modified to promote bone cell growth in the lab and, later on, to guide the formation of natural bone in the body. This granular material also plays a mechanical role while resisting deformation under compressive loads as high as 1,000 kilos.
Looking to the future, tissue engineered bone may not be limited to repairs within or around existing bones. "The goal is to be able to replace entire bone segments," van Blitterswijk says, citing femurs as a long-term possibility. Full-segment bone scaffolds, however, need to hold up to larger and more complex loads—not just compressive but torsional, too. Pointing out that human bone exhibits an elusive balance of stiffness and ductility, van Blitterswijk says that the ideal materials for large scaffolds will need higher fatigue and tensile strength than the granular bone scaffold materials.
Injection molded thermoplastics may fill the bill. IsoTis scientists have been working with researchers at Portugal's University of Minho to injection mold bone scaffolds from composites of cornstarch-based thermoplastics and ceramics. The biodegradable polymers blend various amounts of starch with ethyl vinyl alcohol (SEVA), while the ceramic component is hydroxylapatite (HA). With the HA at 30% by weight, these SEVA/HA composites have achieved a modulus as high as 7 GPa, according to Professor Antonio Cunha, a polymer scientist at the University of Minho. "That stiffness matches the minimum value of human bone," he says. Yet in a trade-off that underscores the difficulties in mimicking human bone, HA levels above roughly 20% also tend to sacrifice the natural ductility of thermoplastics.
To maintain these properties in the right balance, Cunha and his colleagues use a molding machine that can oscillate the molten polymer inside the cavity during the holding stage. According to Cunha, the high shear conditions induced by melt oscillations create parts with a highly oriented microstructure that not only improves stiffness and ductility but also replicates the anisotropic behavior of real bone.
So far, the efforts with starch-based thermoplastic composites have reached only the lowest edge of human bone's mechanical property range. But van Blitterswijk is hopeful that continuing research will someday boost mechanical properties up to the middle of the range, which would open up all sorts of bone replacement applications. "We still have a way to go," he says. "But we'll get there."