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3D Printing of Cell Laden Biomimetic Materials and Biomolecules for Joint Regeneration

Periodic Reporting for period 3 - JointPrinting (3D Printing of Cell Laden Biomimetic Materials and Biomolecules for Joint Regeneration)

Reporting period: 2018-09-01 to 2020-02-29

Osteoarthritis (OA), the most common form of arthritis, is a serious disease of the joints affecting nearly 10% of the population worldwide. The disease represents a significant economic burden to patients and society in Europe, with the cost of OA per patient calculated to exceed €10,000 per annum. At present the treatment options for OA are limited to surgical replacement of the diseased joint with a prosthesis. While this procedure is well established, it is not without its limitations and failures are not uncommon. Joint replacement prostheses also have a finite lifespan, making them unsuitable for the growing population of younger and more active patients requiring treatment for OA. In recent years there has been increased interest in the use of cell based therapies for the treatment of small focal cartilage defects within synovial joints such as the knee. While significant progress has been made in this field, realising an efficacious therapeutic option for the treatment of OA remains elusive and is considered to be one of the greatest challenges in the field of orthopaedic medicine. The objective of this proposal is to use 3D bioprinting to generate anatomically accurate, mesenchymal stem cell (MSC) laden biological implants that can be used to regenerate an entire synovial joint such as the knee. If successful, this could lead to a radical new treatment option for diseases such as OA.
This project has three main aims. The first aim of the project is to use 3D printing to create mechanically reinforced, biological implants suitable for articular cartilage regeneration. To this end we have developed a new class of printable material (termed a bioink) by combining different materials together. These bioinks possess mechanical properties comparable to biological tissues such as articular cartilage. Furthermore, these bioinks can be printed with stem cells to produce viable tissues.

The second aim of the project is to develop 3D printed composite implants for large bone defect repair and cartilage repair. To this end we have developed a range of bioinks that can control the release of biological factors capable of instructing cells to perform specific functions. We have used these bioinks to accelerate vascularization of printed implants in vivo.

The third and final aim of the project is to scale-up the printed implants developed as part of aims 1 and 2 of the project to enable whole joint regeneration. To this end we have used computational tools to help inform the design of implants that would possess the necessary mechanical properties to perform this function. Furthermore, we have used medical imaging data to produce implants that mimic the geometry of different synovial joints.
To date, the progress beyond the state of the art includes:
1. Using 3D printing to develop fibre reinforced biomaterials that mimic the mechanical properties of articular cartilage.
2. The development of bioinks that can be used to control the release of regulatory factors from 3D printed implants.
3. The development of printed biomaterials containing gradients in regulatory factors that promote rapid vascularization of the implant in vivo.
4. The development of computational tools to model the mechanical behavior of 3D printed implants.

By the end of the project we expect to have:
1. Developed a range of printable biomaterials that mimic the mechanical properties of different soft biological tissues.
2. Demonstrated that such printed biomaterials support stem cells to produce different tissue types.
3. Developed printed biological implants that can support vascularization and the regeneration of critically sized bone defects.
4. Developed printed biological implants that can enhance the regeneration of osteochondral defects within synovial joints such as the knee.
5. Developed printed biological implants that can be used to regenerate the entire surface of a synovial joint.