Autologous Freeze-Dried, Platelet-Rich Plasma Carrying Icariin Enhances Bone-Tendon Healing in a Rabbit Model

Abstract

Background: Tendon-bone interface (TBI) injuries are common in sports activities. Owing to the limited regenerative ability of the TBI, its functional healing remains a difficulty in clinical practice. Icariin (ICA) provides strong stimulation for osteogenesis. Platelet-rich plasma (PRP) can be used as a carrier for bioactive molecules, although its ability to provide sustained release for such molecules needs improvement. Hypothesis: Freeze-dried PRP (FD-PRP) as a carrier for ICA can provide sustained release of ICA into the tendon-bone (T-B) healing site, thus accelerating T-B healing. Study Design: Controlled laboratory study. Methods: A total of 84 New Zealand rabbits with partial patellectomy in the hindlimb were randomly allocated into 3 different treatments: ICA incorporated with FD-PRP (ICA/FD-PRP), FD-PRP alone (FD-PRP), or saline control (CTL). The rabbit patella–patellar tendon (PP) interfaces were postoperatively harvested at postoperative week 8 or 16 for gross, radiological, histological, and mechanical evaluations. Results: Our results showed that FD-PRP can act as a carrier for sustained release of ICA into the T-B healing site. Macroscopically, no signs of infection or osteoarthritis were shown in the regenerated PP interfaces, and the area of cartilaginous metaplasia in the FD-PRP and ICA/FD-PRP groups at postoperative week 16 was significantly larger than that of the CTL group (P < .05 for all). Radiologically, micro–computed tomography showed that new bone which formed at the healing site in the ICA/FD-PRP group was significantly increased, remodeled, and mineralized in comparison with the CTL group (P < .05 for all). Histologically, the ICA/FD-PRP group exhibited a significant native PP interface, as shown by the enlargement and remodeling of new bone, well-organized collagen fibers, and robust production of proteoglycans in the regenerated fibrocartilage. The mechanical strength of the regenerated PP interface was significantly improved in the ICA/FD-PRP group. Significantly higher failure load and stiffness were shown in the ICA/FD-PRP group compared with the CTL and FD-PRP groups, respectively (P < .05 for all). Conclusion: FD-PRP is a suitable sustained-release carrier for ICA, and ICA/FD-PRP can provide sustained release of ICA into the T-B healing site, thus effectively accelerating T-B healing. Clinical Relevance: Findings of this study demonstrate the feasibility of using FD-PRP as a carrier for ICA to improve T-B healing and provide a foundation for future clinical application.