Tissue engineering approaches for osteoarthritis

Abstract

With the ageing of the population and the major advances in targeted drug treatments, there is in medicine a shift in attention from survival towards quality of life. Therefore new challenges are emerging in modern health care. Preventive and personalized medicine have been identified as key steps in this context. New targeted biologicals for musculoskeletal diseases such as chronic arthritis have entered daily clinical practice, thereby not only controlling symptoms and signs, inflammation and destruction, but also maintaining function of the joints. The last aspect is essential for the independence of the individual and critical for the quality of life. Since the lifespan of prosthetic devices will always remain limited, new treatment approaches to repair skeletal structures need to be devised for the young and middle aged individuals with skeletal and joint damage caused by either congenital, traumatic, or inflammatory conditions. It is believed that regenerative medicine and more specifically tissue engineering may fill this void to some extent. Indeed, recent cellular therapeutics and combination products, now resorting under a new regulatory class of Advanced Medicinal Therapeutic Products, provide indications that progress is being made with clinically relevant outcomes in well-defined patient populations. For osteoarthritis, a joint disease leading to joint decompensation, novel tissue engineering therapies are being explored and, although most of the developments are still in early phase clinical studies, there are sufficient positive signals to pursue these novel therapeutic approaches in clinics. This article is part of a Special Issue entitled “Osteoarthritis”.

Introduction

Osteoarthritis (OA) is the most common form of chronic arthritis, and is a major cause of pain, disability and loss of quality of life. OA can better be defined as a group of “osteoarthritic diseases” since its cause, clinical presentation and pattern of joint involvement are highly variable. Although the majority of the patients show slow disease progression and never need joint replacement there is nonetheless an important loss in quality of life. Joint prosthesis is a successful treatment for end stage disease but, with an average lifespan of 10–15 years, is not such an attractive solution for younger (less than 55 years old) patients. Therefore, we need to come up with more creative and innovative treatment approaches, in particular for the “young” and fast progressing OA patients. However, as of today there is no treatment that appears to do so, in contrast to major progress in disease modifying treatments for other chronic arthritic diseases such as rheumatoid arthritis. Can we design treatments or interventions that bridge the gap between conservative symptomatic treatments and joint prosthesis? It is believed that besides inhibition of breakdown processes, regenerative and tissue engineering approaches may be filling this void. In addition, there is the hope that these anabolic and repair strategies may prevent in early damaged joints the evolution towards OA, and thus have long term impact on disease prevalence and progression, particularly in individuals at risk [1], [2].

Regenerative medicine and tissue engineering seek to repair or regenerate damaged tissues and organs, regardless of the cause of the damage, without leaving scar tissue behind, and restoring both structure and function of the damaged tissues/organs. Nature demonstrates, over and over again, that this can be successful as wound healing and fracture repair are typically processes that happen routinely and successfully in the postnatal individual, even until advanced age. Indeed, in many patients it is not possible to detect after the healing process where the skin wound or fractured bone site was. We also know, as demonstrated in fetal surgery, that this scarless repair is partially age and context dependent. Thus, it is attractive to envision that with an improved and in depth understanding of the repair processes at the cellular and molecular level, we may be able to interfere quickly at the time of injury, and guide the healing process more appropriately thereby preventing scar formation. Postnatal tissue healing mimics developmental processes of tissue formation. As an example, and of relevance for skeletal tissues, it appears that the process of rebuilding an adult limb has many similarities with how the limb forms in the first place in the embryo, and this requires signaling mechanisms to specify the final pattern. Thus, both limb formation and limb regeneration are likely to employ the same molecular pathways [3], with the limitation that in the postnatal individual inflammation and the immune system will interfere. The remarkable advances in developmental biology over the last decades have provided the knowledge platform to advance into novel regenerative medicine approaches in postnatal life. In view of the above, we are now in a position to enter a new era in regenerative medicine and tissue engineering [4], [5]. In this article we will briefly review the approaches seeking to repair skeletal tissues and more in particular damaged joints, and with that experience move on to novel treatment opportunities for early and established osteoarthritic joints.