Semi-Bone Tunnel Technique Using Double-Row Suture Bridge Combined With Platelet-Rich Plasma Hydrogel for Rotator Cuff Repair in a Rabbit Model.

BACKGROUND: The approach to managing the footprint area and reconstructing the tendon-bone interface (TBI) is critical for optimal healing. PURPOSE: To evaluate the outcomes of the semi-bone tunnel (SBT) technique using a double-row suture bridge combined with platelet-rich plasma (PRP) hydrogel for rotator cuff repair in a rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 48 New Zealand White rabbits were divided into 4 groups. The supraspinatus tendons were severed at the footprint to create a rotator cuff tear model in the surgical groups. Rabbits were treated with the traditional onto-surface repair (control group), SBT technique (SBT group), and SBT technique combined with PRP hydrogel implantation (SBT+PRP group). The rabbits without surgery were the normal group. At 8 weeks after surgery, macroscopic observation, magnetic resonance imaging (MRI) and micro-computed tomography (µCT) examinations, histological evaluations, and biomechanical tests were performed to assess the curative effects of the given treatments. RESULTS: The MRI results showed that the repaired supraspinatus tendon presented a uniform signal, minimal inflammatory response, and the lowest signal-to-noise quotient value in the SBT+PRP group. The µCT results suggested that the SBT technique did not reduce the local bone mineral density in the TBI area compared with the onto-surface repair technique. The histological staining results showed that the regenerated TBI in the SBT+PRP group had a 4-layer structure similar to the natural tissue. The highest values for biomechanical properties were observed in the SBT+PRP group, and there was no significant difference between the SBT+PRP group and normal group. CONCLUSION: The SBT technique presented a better tendon-bone healing effect for rotator cuff tear in the rabbit model compared with the traditional onto-surface repair technique. The specimens in the SBT+PRP group had a similar TBI structure and biomechanical properties to the natural tissue. CLINICAL RELEVANCE: The SBT technique can be an alternative surgical approach for rotator cuff repair, especially for moderate to large tears and cases requiring scaffold implantation.

Engineered exosomes: A promising strategy for tendon-bone healing.

BACKGROUND: Due to the spatiotemporal complexity of the composition, structure, and cell population of the tendon-bone interface (TBI), it is difficult to achieve true healing. Recent research is increasingly focusing on engineered exosomes, which are a promising strategy for TBI regeneration. AIM OF REVIEW: This review discusses the physiological and pathological characteristics of TBI and the application and limitations of natural exosomes in the field of tendon-bone healing. The definition, loading strategies, and spatiotemporal properties of engineered exosomes were elaborated. We also summarize the application and future research directions of engineered exosomes in the field of tendon-bone healing. KEY SCIENTIFIC CONCEPTS OF REVIEW: Engineered exosomes can spatially deliver cargo to targeted sites and temporally realize the sustained release of therapeutic molecules in TBI. This review expounds on the multidifferentiation of engineered exosomes for tendon-bone healing, which effectively improves the biological and biomechanical properties of TBI. Engineered exosomes could be a promising strategy for tendon-bone healing.

A novel SERPINE1-FOSB fusion gene in pseudomyogenic hemangioendothelioma results in activation of intact FOSB and the PI3K-AKT-mTOR signaling pathway and responsiveness to sirolimus.

Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare disease that affects mainly the young and more men than women. PHE are multicentric, locally aggressive, have low metastatic potential, and affect multiple tissue planes. Genetic aberrations are frequently detected in PHE and may play important roles in the occurrence, development, and treatment of this disease. In this study, we report a case of PHE with a novel SERPINE1-FOSB fusion gene. The fusion introduced a strong promoter near the coding region of FOSB, resulting in overexpression of intact FOSB. Immunohistochemical analysis showed overexpression of pAKT and mTOR in tumor cells, suggesting activation of the PI3K-AKT-mTOR signaling pathway. The patient responded well to targeted therapy with sirolimus, an mTOR inhibitor. Our study correlated dysregulation of a specific signaling pathway and the effectiveness of a targeted therapy to a specific genetic aberration. This information may be useful for future investigations of targeted therapeutics and provide a potential predictive biomarker for therapeutic effectiveness in PHE cases.

Combination of graphene oxide and platelet-rich plasma improves tendon-bone healing in a rabbit model of supraspinatus tendon reconstruction.

The treatment of rotator cuff tear is one of the major challenges for orthopedic surgeons. The key to treatment is the reconstruction of the tendon-bone interface (TBI). Autologous platelet-rich plasma (PRP) is used as a therapeutic agent to accelerate the healing of tendons, as it contains a variety of growth factors and is easy to prepare. Graphene oxide (GO) is known to improve the physical properties of biomaterials and promote tissue repair. In this study, PRP gels containing various concentrations of GO were prepared to promote TBI healing and supraspinatus tendon reconstruction in a rabbit model. The incorporation of GO improved the ultrastructure and mechanical properties of the PRP gels. The gels containing 0.5 mg/ml GO (0.5 GO/PRP) continuously released transforming growth factor-ß1 (TGF-ß1) and platelet-derived growth factor (PDGF)-AB, and the released TGF-ß1 and PDGF-AB were still at high concentrations, ∼1063.451 pg/ml and ∼814.217 pg/ml, respectively, on the 14th day. In vitro assays showed that the 0.5 GO/PRP gels had good biocompatibility and promoted bone marrow mesenchymal stem cells proliferation and osteogenic and chondrogenic differentiation. After 12 weeks of implantation, the magnetic resonance imaging, micro-computed tomography and histological results indicated that the newly regenerated tendons in the 0.5 GO/PRP group had a similar structure to natural tendons. Moreover, the biomechanical results showed that the newly formed tendons in the 0.5 GO/PRP group had better biomechanical properties compared to those in the other groups, and had more stable TBI tissue. Therefore, the combination of PRP and GO has the potential to be a powerful advancement in the treatment of rotator cuff injuries.

Effects of geranylgeranylacetone upon cardiovascular diseases.

Heat shock proteins (HSPs) are an important family of protective proteins. They are involved actively in an array of cellular processes, including protective effects on the cardiovascular system in response to various stimuli. Increasing evidence shows that pharmacologic interventions that induce expression of HSPs may be a novel approach for the treatment of cardiovascular diseases. However, agents that induce expression of HSPs used previously are toxic or have harmful side effects, which limit their clinical application. Geranylgeranylacetone (GGA) is not only a widely used antiulcer agent in Asia, but also a nontoxic inducer of HSPs expression. It increases the expression of HSPs rapidly in the presence of ischemia, anoxia, oxidative stress, and toxicants, thereby having significant protective effects. The cardioprotective effects of GGA have been corroborated by experiments in vivo and in vitro. Importantly, several derivatives of GGA have been synthesized that have improved pharmaco-chemical and HSPs-boosting properties. In this review, the current knowledge and potential cardioprotective mechanisms of GGA are summarized comprehensively. We discuss the protective effects of GGA in cardiovascular diseases and myocardial injury induced by physical or chemical injury. Currently available information suggests that GGA could be employed as a novel pharmacologic intervention against cardiovascular disease.