There is burgeoning worldwide interest in developing replacements for human tissue types—“every single one of them”—said Mikos, who specializes in orthopedic applications. He said that laboratories are investigating ophthalmic, neurologic, cardiovascular, musculoskeletal and skin tissues, among others.
Because some of the demand for tissue engineering has been driven by war injuries, the Department of Defense has created the Armed Forces Institute of Regenerative Medicine, which has supported one of Mikos’s projects for the past 4 years.
The paradigm currently being pursued by the field has three parts, Mikos explained: biomaterials, which include both natural and synthetic polymers, as well as ceramics and metals; drugs, which can stimulate the growth of desired populations of cell types; and cells, which can be engineered to promote tissue growth.
In the latter category, the main focus nowadays is on stem, or progenitor, cells, said Mikos; earlier work had focused on so-called “committed” cells. Defining the roles of different cell populations in tissue engineering remains a major challenge, he added.
Mikos said there is burgeoning worldwide interest in developing replacements for human tissue types—“every single one of them.”
Photos: Michael Spencer
Scientists are building 3-D polymer scaffolds and cell-scaffold constructs where details such as pore architecture can modulate cell fate, Mikos explained. Almost all of the work he described relies on animal models: stem cells transplanted into rats have prompted bone growth; bone engineering in the ribs of sheep has progressed, with the goal of creating vascularized bone tissue; and bone tissue induction into nano-composite scaffolds has been shown in the leg bones of rabbits.
“The biggest challenge in biomaterials,” Mikos said, “is the evaluation and validation [of tissue engineering] in relevant animal models.”
A special challenge in bone work is literal hardness— the material must be capable of bearing loads. Researchers are crafting carbon nanotube composites that are comparable to human bone, Mikos said.
Another problem is the dispersion of nanomaterials within a scaffold. Scientists are using various chemical techniques to overcome that difficulty, Mikos said.
Researchers must also determine what happens to non-degradable materials once they are introduced into bodies. “Are they excreted? Integrated? Or could they migrate and do harm?” Mikos asked.
Interestingly, some tissue engineering, in addition to providing structural and biological benefit, also happens to improve cellular imaging, using magnetic resonance and computed tomography, Mikos said. “Three-dimensional tissue imaging in a non-destructive way is allowing insight into osteogenesis and angiogenesis.”
Of particular interest to his lab in the past 7 years have been improvements in bioreactor technology, which had traditionally been used to expand populations of specific cell types. The so-called “flow perfusion bioreactor” can be used to generate an extracellular matrix that is rich in signaling molecules, Mikos said. Such matrices can convert an inert material such as titanium into a “bioreactive” body component.
Mikos surveyed a host of other promising research avenues: using “biomimetic hydrogels” to guide bone regeneration in dental applications; and using “particulate polymer carriers” to deliver bioactive molecules.
“Dose is a very important parameter” in these instances, he cautioned, “plus a knowledge of release kinetics.”
Of special interest to those with aching, aging knees, Mikos said that genetically modified cells may one day be able to regenerate bone, and that injectable cellular constructs and growth-factor carriers may soon prompt restoration of cartilage.
If people can just hold out long enough, the science Mikos described may one day be able to maintain our sagging spaces, rebuild our shaky joints, fill in any skeletal absences and get us all back out on the battlefield of life.