Prosthetic jaw joint
The temporomandibular joint (TMJ) forms the back of the lower jaw and connects the jaw to the skull, it is an anatomically complex and highly loaded structure consisting of cartilage and bone. In the USA alone, about 10 million people suffer from TMJ dysfunction due to birth defects, injuries or diseases. Current treatments range from steroid injections, which provide temporary pain relief, to surgical reconstructions using prostheses or donor tissue, and often do not provide long-term recovery. The researchers wanted to find a better way to treat TMJ, including the use of biological transplants grown in the laboratory, which could integrate with natural tissues and eventually ensure lifelong functioning.
A multidisciplinary team of researchers from Columbia University, Columbia College of Dental Medicine, Louisiana State University has created bioengineered TMJ transplants from adipose tissue stem cells that are exactly suitable for the recipient, both biologically and anatomically. The new study was conducted on the basis of a long series of their previous developments in the field of cartilage and bone bioengineering for regenerative medicine and the creation of tissue models of diseases.
Histological section of cartilage tissue. Morphology of a bioengineered graft 6 months after implantation (left) compared to a native graft (right). The fibrous, proliferative and hypertrophic layers are clearly visible.
To develop a methodology for TMJ reconstruction using the recipient's own cells, the authors used dwarf pigs. The group isolated stem cells from a small amount of adipose tissue taken from each animal, increased the number of cells in the culture to get enough for a large transplant, and induced them into chondroblasts and osteoblasts. Using imaging-controlled fabrication, the researchers transformed the block from a clinically used cell-free (dncellularized) bovine bone matrix into the exact geometry of the restored TMJ. They filled this framework with osteoblasts, stimulating the formation of cartilage by compacting the surface layer of condensed mesenchymal cells with a thickness of 1 mm. The researchers built the bioreactor chamber in such a way that the frame fits tightly into it, like a hand in a glove.
Schematic representation of a bone-cartilage graft in a bioreactor.
Since cartilage and bone are formed in different environmental conditions, a specialized bioreactor was required for the formation of TMJ transplants, which would provide a separate supply of nutrient medium for bone and cartilage to two areas of tissue. The researchers optimized the perfusion of the nutrient medium through the bone and the flow along the surface of the cartilage to meet completely different nutritional and environmental needs for the two tissues.
Video modeling of the perfusion of the medium through the bone part of the cultured graft and the flow of the medium along the surface of the cartilage.
After all these difficult conditions were met, the group implanted individualized TMJ grafts in experimental animals for six months to determine the ability of the grafts to structurally and functionally replace the native joint.
Six months later, the grafts had a multi-layered structure similar to the structure of native joints, successfully integrated with surrounding tissues and provided biological and mechanical function of the native joint. The authors believe that this technique can be used for bioengineering other joints and creating high-precision models for studying joint diseases.
The general morphology of the bioengineered temporomandibular joint 6 months after implantation (left) compared with its own joint (right). The cartilaginous and bony areas are clearly visible.
The use of a bioreactor with a double flow was crucial for the formation of composite bone-cartilage grafts. In it, each tissue was preserved in its own "cradle", while maintaining communication through diffusion factors, as in a living organism.
The researchers emphasize that more work needs to be done before TMJ transplants adapted to the individual needs of patients become a clinical reality. To fully understand the process of tissue remodeling, research over longer periods of time is needed. In addition, the researchers are interested in expanding their methodology to study the diversity of the patient population and to study the restoration of the temporomandibular joint depending on age, gender, the presence of skeletal diseases or related systemic conditions.
Article D.Chan et al. Tissue engineered autologous cartage-bone grafts for temporomandibular joint regeneration is published in the journal Science Translational Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on Columbia Engineering: Researchers Use Lab-grown Tissue Grafts for Personalized Joint Replacement.