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.

Freeze-Drying of Platelet-Rich Plasma: The Quest for Standardization

“…Pioneering studies using commercial trehalose-treated lyophilized platelets in equine research models similar gene activation than fresh-frozen PRP in tendon cell cultures [57]. Furthermore, FD-PRP is an effective carrier for icariin, and accelerated tendon-bone healing in New Zealand rabbits with partial patellectomy, as assessed by histology and mechanical testing [58]. Additionally, the use of polydioxanone fibers containing FD-PRP in volumetric muscle loss caused a dose-and ERK-dependent effect in myogenic differentiation [59].…”

The Enhancement Effect of Acetylcholine and Pyridostigmine on Bone-Tendon Interface Healing in a Murine Rotator Cuff Model

“…Approaches including stem cells, bioactive factors, scaffolds, and other biophysical therapies have been used to promote the regeneration of fibrocartilage. 8,23,40,44,46 However, the parasympathetic nervous system and its major neurotransmitter ACh have not been studied in this field.…”

“…Promising results have been demonstrated in many preclinical experimental studies. 8,9,23,27,29,46 However, much work is needed before these applications can be used in clinical practice.…”

Enhancement of Rotator Cuff Tendon-bone Healing with Graphene Oxide/PRP Composite Scaffold in a Rabbit Model: A Histological and Biomechanical Study

“…Reviewing the article, there were also other biomaterials used to enhance TBH. Due to the functional halflife and rapid dispersal in vivo, various growth factors released from PRP induces more scar tissue formation on the TBI, thus not improving the mechanical properties of the regenerated tissue [7,26]. Therefore, controlled and sustained release is required [5].…”

“…The interface matures with time, and the stiffness of the GO group is increasing at 8 and 12 weeks (P < 0.05), while there was no difference between PRP and Control groups (P > 0.05). Recently, several studies [26,31,34,35] demonstrated that the application of fresh PRP alone could improve the integrity of repair sites, but the enhancement of biomechanical properties remained controversial, and even no demonstrable effect. This study used GO for the steady, controlled, and sustained release of PRP's various growth factors.…”