Research centered at Columbia University is starting to improve techniques that combine ceramic scaffolds and stem cells to “grow” dental implants and limb joints.
Led by Jeremy Mao, the work was carried out in the Tissue Engineering and Regenerative Medicine Lab at Columbia, and involves colleagues from the University of Missouri and Clemson University.
In the dental example, the group has been looking at alternatives to traditional tooth implant approaches that involve attaching an artificial tooth to a titanium post implanted in a patients jaw. These post/tooth combinations require many months of healing and are prone to failures, particularly if the jaw bone doesn’t adequately anchor the post. Mao and his group, instead, have been testing a method that begins with the formation of an anatomically shaped rat incisor scaffolds that are made by 3D bioprinting using poly-ε-caprolactone and hydroxyapatite. The scaffolds have 200-µm-diameter interconnecting microchannels that contain stem cell-recruiting substances (stromal-derived factor-1 and bone morphogenetic protein-7). The scaffolds are then implanted in the rats’ jaw bone at a site where an incisor had previously been extracted. They report that after just 9 weeks, periodontal ligament and new bone regenerates.
“These findings represent the first report of regeneration of anatomically shaped tooth-like structures in vivo, and by cell homing without cell delivery,” says Mao and other authors in a paper published in the Journal of Dental Research. “The potency of cell homing is substantiated not only by cell recruitment into scaffold microchannels, but also by the regeneration of periodontal ligaments and newly formed alveolar bone.”
With his joint work, Mao is researching techniques to regrow long-lasting joints “naturally,” instead of using artificial joint implants. Mao and his team have first looked at regenerating hip joints in mature rabbits. They use a CAD system that uses a laser scan to measure the surface contours of the hip joint (actually, the humeral head). The data is then used by the bioprinter to create a 3D joint scaffold upon which cartilage and bone can be regenerated. As with the tooth example, the joint scaffold is infused with growth factors to stimulate stem cells to migrate to the scaffold. The humeral head is then surgically excised and replaced with bioscaffold.
They report in The Lancet that this approach allows them to grow over a four-month period a functioning synovial joint grown with the animals own stem cells. In some test groups, the rabbits are able to resume weight bearing and locomotion three to four weeks after surgery.
Mao’s group reports that four-month-old bioscaffolds are fully covered with hyaline cartilage in the articular surface. Compressive and shear properties are the same as native articular cartilage, and it is integrated with regenerated bone that had good blood vessel growth.
As far as performance goes, they subjected the joint to stress tests, and they report that it performed as well as as native articular cartilage. In other words, after four months of growth, the research yielded a fully functioning leg with a new joint that was grown using the animal host’s own stem cells, instead of stem cells that were harvested apart or outside of the host.