A Bone-Penetrating Precise Controllable Drug Release System Enables Localized Treatment of Osteoporotic Fracture Prevention via Modulating Osteoblast-Osteoclast Communication.

Improving local bone mineral density (BMD) at fracture-prone sites of bone is a clinical concern for osteoporotic fracture prevention. In this study, a featured radial extracorporeal shock wave (rESW) responsive nano-drug delivery system (NDDS) is developed for local treatment. Based on a mechanic simulation, a sequence of hollow zoledronic acid (ZOL)-contained nanoparticles (HZNs) with controllable shell thickness that predicts various mechanical responsive properties is constructed by controlling the deposition time of ZOL and Ca2+ on liposome templates. Attributed to the controllable shell thickness, the fragmentation of HZNs and the release of ZOL and Ca2+ can be precisely controlled with the intervention of rESW. Furthermore, the distinct effect of HZNs with different shell thicknesses on bone metabolism after fragmentation is verified. In vitro co-culture experiments demonstrate that although HZN2 does not have the strongest osteoclasts inhibitory effect, the best pro-osteoblasts mineralization results are achieved via maintaining osteoblast-osteoclast (OB-OC) communication. In vivo, the HZN2 group also shows the strongest local BMD enhancement after rESW intervention and significantly improves bone-related parameters and mechanical properties in the ovariectomy (OVX)-induced osteoporosis (OP) rats. These findings suggest that an adjustable and precise rESW-responsive NDDS can effectively improve local BMD in OP therapy.

Exposure to radial extracorporeal shockwaves induces muscle regeneration after muscle injury in a surgical rat model.

The leading cause of training interruption in sport is a muscle injury, for which the standard treatment is nonsteroidal anti-inflammatory drugs (NSAIDs). To find alternative treatments, we investigated whether the radial extracorporeal shockwave application (rESWT) could stimulate muscle regeneration. A lesion with complete rupture (grade III muscle tear) was set in the musculus rectus femoris of 12-week-old Wistar rats, and the NSAID diclofenac, rESWT, or a combined therapy were applied on day 0, 3, and 5 directly following the surgery. Rats were euthanized at 2, 4, and 7 days after surgery and the area of muscle lesion was excised for histological and gene expression analysis to determine the progress in the healing of damaged fibers and tissue regeneration. The best effect on muscle regeneration was observed in the group treated with rESWT alone. Monotherapy by diclofenac showed a smaller but still positive effect and lowest effects were detected when both therapies were applied. rESWT alone demonstrated a significant upregulation of the muscle markers MyoD and myosin. The presence of myosin gene expression indicated newly formed muscle fibers, which was confirmed by hematoxylin and eosin staining. Seven days after injury the amount of mononucleated cell decreased and regenerating fibers could be detected. This effect is most pronounced in the group treated with rESWT alone. In our study, shockwaves demonstrated the best effect on muscle regeneration. Therefore, we recommend prospective clinical studies to analyze the effect of rESWT after sports trauma to improve muscle regeneration and to shorten the rehabilitation.