Abstract
Subtalar osteoarthritis (STOA) is often secondary to chronic ankle sprains, which seriously affects the quality of life of patients. Due to its etiology and pathogenesis was not studied equivocally yet, there is currently a lack of effective conservative treatments. Although they have been used for tissue repair, platelet-rich plasma-derived exosomes (PRP-Exo) have the disadvantage of low retention and short-lived therapeutic effects. This study aimed to determine whether incorporation of PRP-Exo in thermosensitive hydrogel (Gel) increased their retention in the joint and thereby playing a therapeutic role on STOA due to chronic mechanical instability established by transecting lateral ligaments (anterior talofibular ligament (ATFL)/calcaneal fibular ligament (CFL)). PRP-Exo incorporated Gel (Exo-Gel) system, composed of Poloxamer-407 and 188 mixture-based thermoresponsive hydrogel matrix in an optimal ratio, was determined by its release ability of Exo and rheology of Gel response to different temperature. The biological activity of Exo-Gel was evaluated in vitro, and the therapeutic effect of Exo-Gel on STOA was evaluated in vivo. Exo released from Exo-Gel continuously for 28 days could promote the proliferation and migration of mouse bone mesenchymal stem cells (mBMSCs) and chondrocytes, at the same time enhance the chondrogenic differentiation of mBMSCs, and inhibit inflammation-induced chondrocyte degeneration. In vivo experiments confirmed that Exo-Gel increased the local retention of Exo, inhibited the apoptosis and hypertrophy of chondrocytes, enhanced their proliferation, and potentially played the role in stem cell recruitment to delay the development of STOA. Thus, Delivery of PRP-Exo incorporated in thermosensitive Gel provides a novel approach of cell-free therapy and has therapeutic effect on STOA.Graphical
Highlights
Ankle sprain is the most common injury related to physical activity and athletic participation, accounting for about 60% of all injuries in interscholastic sports [1, 2]
The Exo cargo was analyzed, and it was found that Platelet-rich plasma (PRP)-Exo contained Transforming growth factor β1 (TGFβ1), Platelet derived growth factor BB (PDGFBB), vascular endothelial growth factor (VEGF) and Stromal cell derived factor-1 (SDF-1)
Our results as well highlighted that the retention of platelet-rich plasma-derived exosomes (PRP-Exo) in the ankle was improved by this Gel, which temporarily stored Exo and prevented fast diffusion of Exo out of the joint
Summary
Ankle sprain is the most common injury related to physical activity and athletic participation, accounting for about 60% of all injuries in interscholastic sports [1, 2]. Unlike a major breakthrough in molecular pathophysiological research in knee OA due to the establishment of surgically induced mouse knee OA models in 2005 [9,10,11], only a few of studies [12, 13] have reported that mechanical instability could be induced in the ankle joint in this mouse model by removal of anterior talofibular ligament (ATFL)/calcaneal fibular ligament (CFL) on its lateral side, to provide a reliable animal model of subtalar OA (STOA). Such studies substantially promote the development of ankle joint research, the molecular mechanisms of cartilage homeostasis in subtalar joint and intervention for acute lateral ankle sprains are still rarely studied
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