Lorenzo Moroni and his team at University of Maastricht's Institute for Technology-Inspired Regenerative Medicine (MERLN) in The Netherlands, use 3D bioprinting to create "smart scaffolds," which they seed with patient stem cells and growth factors to produce structures that behave like natural cartilage tissues.
Humans start walking a little before the age of one, and after decades of putting one foot in front of the other joints start to wear out, especially in the knees. A promising clinical trial underway shows that bioprinted cartilage, seeded by patients' own cells, may provide relief.
Joint wear and tear often breaks down fibrocartilage, fibrous bundles of cartilage such as the menisci, labra, and intervertebral discs, which are the "shock absorber" layers of cartilage next to the bone. This condition, osteoarthritis, leaves patients with chronic pain.
There are two ways to approach joint pain. Surgical treatments range from smoothing joint movement by debriding (or scraping) the cartilage surface to total knee replacement. These treatments have a proven record, but they often have a limited lifespan and may require prolonged rehabilitation.
The other approach is to fortify existing cartilage through tissue regeneration. The most common, at least until now, involves grafting cartilage from healthy areas of a patient's body or from a cadaver onto the stricken bones and joints. A third method, autologous chondrocyte implantation (ACI), is a multi-stage procedure where healthy cartilage cells are implanted into the degenerated tissue.
While tissue regeneration preserves natural cartilage and bone, it comes with caveats. It is used most often in younger patients who have small, isolated regions of damage. There is a limited supply of cadaver grafts and they may carry disease. Using patient material may create defects in other parts of the body. All three techniques, including ACI, are temporary fixes that degenerate within a few years, resulting in a return to pain and limited mobility for patients.
To regenerate long-lasting, mechanically strong cartilage and bone, Lorenzo Moroni, a principle investigator at University of Maastricht's Institute for Technology-Inspired Regenerative Medicine (MERLN) in The Netherlands, has turned to bioprinting.
Bioprinting uses additive manufacturing techniques to print plastic skeleton-like 3-D "smart scaffolds," which he seeds with patient stem cells and growth factors to produce structures that behave like natural cartilage tissues.
The scaffolds are engineered to apply the mechanical and physical forces needed to prompt the stem cells to differentiate into specific types of cells. These forces, enhanced by the right growth factors, may cause stem cells to form cartilage, bones, muscles, or other types of tissues.
"The rationale behind bioprinting is to provide a hierarchical mechanical support to cells during tissue regeneration, while at the same time engineering the surface properties of the materials with which the cells come into contact to improve the biological response of the cells themselves," Moroni says.
Thanks to methodical experimentation, Moroni has built a library of scaffold materials, porosity, and structures optimized to produce certain types of tissues.
To rebuild joint tissue, Moroni and his colleagues first image a patient's joint using computed tomography (CT) or magnetic resonance imaging (MRI). They program information obtained from the CT or MRI into the CAD model.
Moroni's team uses the CAD model to design a scaffold that will fill and repair the damaged area.
To mimic bone and cartilage, "the scaffolds need to be strong, yet flexible," Moroni says. By using a combination of two different polymers, the researchers can offer an appropriate balance between softness and stiffness. They also vary porosity and pore size to determine how well cells thrive in the environment.
The researchers then take biopsies of cartilage tissue from a patient's healthy joint and add it to a fabricated scaffold.
Maroni has collaborated with Jeanine Hendriks on cellular regeneration. She is founder and chief technology officer of CellCoTec, an orthopedic device company. CellCoTec currently has a multinational clinical trial in progress with patients whose cartilage has been replaced by INSTRUCT, the company’s bioprinted scaffold implant containing cells grown from biopsies of their own healthy joint tissue.
After one year, the tissue formed is similar to real cartilage. Patients have reported improved quality of life based on mobility and pain levels, according to Maroni. Ultimately, the aim is to recreate in synthetic materials the same type of communication between cells and nature's extracellular matrix scaffolding that occurs in the body.
This is critical for creating long-lasting fixes. For example, bone and cartilage interface with one another and other tissues, but they have very different requirements for oxygen (low in cartilage, high in bone). The pore size in a scaffold affects the oxygen concentration and therefore impacts whether or not stem cells can grow.
Read more about 3D Bioprinting on AABME.org.
Moroni's lab also continues to improve their ability to make more natural forms of cartilage. One promising research thrust involves ceramics. Although ceramics have good porosity and cell retention, they often lack mechanical strength. In 2016, Moroni's lab demonstrated flexible yet strong scaffolds electrospun from a solution of yttrium-stabilized zirconia. The process, which looks a bit like spinning cotton candy, uses electrical forces to vary the diameter of long, continuous fiber threads. The resulting scaffolds are stiff at the microscopic scale, but flexible at the macroscale.
The lab late last year published a proof-of-concept paper in Applied Materials and Interfaces that introduces a new technique for direct writing with electrospinning solution. Working with different solutions, ambient conditions, and processing parameters, they produced scaffolds with a variety of aligned, single, and randomly spun fibers. One structure closely resembled the articular cartilage found on the ends of bones that allows joints to move smoothly.
"Ultimately the aim is to be able to recreate that same cell-extracellular matrix communication that occurs in native tissues with synthetic materials, so to steer cell activity during the regeneration and control not only the initiation of this process, but also its maturation," Moroni says.
Melissa Lutz Blouin is an independent technical writer.