Recent advancements in cartilage tissue engineering innovation and translation

Abstract

Articular cartilage was expected to be one of the first successfully engineered tissues, but today, cartilage repair products are few and they exhibit considerable limitations. For example, of the cell-based products that are available globally, only one is marketed for non-knee indications, none are indicated for severe osteoarthritis or rheumatoid arthritis, and only one is approved for marketing in the USA. However, advances in cartilage tissue engineering might now finally lead to the development of new cartilage repair products. To understand the potential in this field, it helps to consider the current landscape of tissue-engineered products for articular cartilage repair and particularly cell-based therapies. Advances relating to cell sources, bioactive stimuli and scaffold or scaffold-free approaches should now contribute to progress in therapeutic development. Engineering for an inflammatory environment is required because of the need for implants to withstand immune challenge within joints affected by osteoarthritis or rheumatoid arthritis. Bringing additional cartilage repair products to the market will require an understanding of the translational vector for their commercialization. Advances thus far can facilitate the future translation of engineered cartilage products to benefit the millions of patients who suffer from cartilage injuries and arthritides.

Figure 1:

Strategies for articular cartilage tissue engineering. To repair cartilages of diarthrodial joints such as the knee, hip, temporomandibular joint, and facet joint, the tissue engineering triad (i.e., cells, stimulation, and scaffold or scaffold-free approaches) are utilized. This figure highlights select areas of interest within the cartilage tissue engineering field. Abbreviation: Temporomandibular joint (TMJ).

Figure 2:

Approaches for tissue engineering cartilage in an inflammatory environment. (Left) In inflamed joints that are afflicted with OA or RA, various degenerative and pathologic changes occur, and immune cells invade. (Right) Various immunomodulatory techniques have been utilized to modulate the immune response within inflamed joints. While many injection-based approaches have been developed, tissue immunoengineering involves the deployment of a mechanically robust implant with immunomodulatory properties. Two categories of treatments that have been developed within the field of tissue immunoengineering include the use of immunomodulatory biomaterials and synthetic biology.

Figure 3:

The translational vector for tissue-engineered cartilage products. This figure summarizes the translational vector from research and development to clinical use from the perspectives of regulation, manufacturing, funding, and intellectual property (IP). A. The aspects of the translational vector must be coordinated in parallel as they influence each other simultaneously in an interconnected manner. For example, an investigator may only be able to secure the appropriate funding to conduct costly clinical trials after IP is established. The three main aspects of the translational vector are B. regulatory, C. manufacturing, and D. funding and intellectual property. Abbreviations: Center for Biologics Evaluation and Research (CBER), Center for Devices and Radiological Health (CDRH), Investigational New Drug (IND), Biologics License Application (BLA), Investigational Device Exemption (IDE), Premarket Approval (PMA), Good Laboratory Practice (GLP), Good Manufacturing Practice (GMP).