Stimulus‐Responsive Drug Delivery Nanoplatforms for Osteoarthritis Therapy

Abstract

Fundamentally degenerative, OA represents a considerably negative impact on the quality of life. [1,2] With an increasingly aging global population, greater numbers of OA patients are representing a clear increase in economic and societal burden. OA is primarily characterized by the degeneration or deterioration of articular cartilage. [3] More specifically, as a result of the excessive recruitment of inflammatory cells at the joint site, [4] matrix metalloproteinase (MMP) [5] and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) [6] are overexpressed during the development of OA, which leads to the destruction of the collagen II network and glycosaminoglycan (GAG). Articular cartilage dysfunction and degradation then eventually result, often presenting with permanent pathologic alterations to the entire joint.Current pharmacological treatments, (primarily focused on pain relief and antiinflammation), and/or surgery, (including microfracture surgery and joint replacement), are the most conventional therapeutic approaches for OA. [1,7] There are several disadvantages to these conventional approaches. Whilst microfracture surgery provides a measure of relief and functional recovery of the smaller-scale joint defects through the local generation of fibrocartilage from bone marrow obtained from the subchondral bone, due to the lower abrasion-resistance ability of fibrocartilage this method is often unsuitable to provide long-term relief, or for situations where large-scale defects have occurred. [8] A number of clinical strategies of joint replacement, including osteochondral autografts or allografts, are also limited by the restricted availability of donor grafts or by complications requiring secondary surgery. [9] Along with the continued development of surgical treatments, more advanced therapeutic methods have also been developed for OA surgery. These include ACI (autologous chondrocyte implantation) and MACI (matrix-induced autologous chondrocyte implantation). However, for ACI, the viability and loss of chondrocytes during the planting procedure seem to be an unavoidable problem. MACI was developed as a potential solution to this, where the in vitro use of a biodegradable (collagen matrix membrane) material as a temporary scaffold for the pre-plantation of chondrocytes could effectively lessen the loss of cells during the process of transplantation. However, for patients of more advanced ages or with too large an area of injury to the cartilage, MACI remains an unsuitable therapeutic approach.Osteoarthritis (OA) is one of the most prevalent age-related degenerative diseases. With an increasingly aging global population, greater numbers of OA patients are providing clear economic and societal burdens. Surgical and pharmacological treatments are the most common and conventional therapeutic strategies for OA, but often fall considerably short of desired or optimal outcomes. With the development of stimulus-responsive nanoplatforms has come the potential for improved therapeutic strategies for...

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