An excess of glucocorticoids (GCs) is reported to be one of the most common causes of osteonecrosis of the femoral head (ONFH). In addition, GCs can induce bone cell apoptosis through modulating endoplasmic reticulum (ER) stress. Among the three main signal pathways in ER stress, the PERK (protein kinase RNA-like ER kinase)/CHOP (CCAAT-enhancer-binding protein homologous protein) pathway has been considered to be closely associated with apoptosis. Platelet-rich plasma (PRP) has been referred to as a concentration of growth factors and the exosomes derived from PRP (PRP-Exos) have a similar effect to their parent material. The enriched growth factors can be encapsulated into PRP-Exos and activate Akt and Erk pathways to promote angiogenesis. Activation of the Akt pathway may promote the expression of anti-apoptotic proteins like Bcl-2, while CHOP can inhibit B-cell lymphoma 2 (Bcl-2) expression to increase the level of cleaved caspase-3 and lead to cell death. Consequently, we hypothesized that PRP-Exos prevent apoptosis induced by glucocorticoid-associated ER stress in rat ONFH via the Akt/Bad/Bcl-2 signal pathway. To verify this hypothesis, a dexamethasone (DEX)-treated in vitro cell model and methylprednisolone (MPS)-treated in vivo rat model were adopted. Characterization of PRP-Exos, and effects of PRP-Exos on proliferation, apoptosis, angiogenesis, and osteogenesis of cells treated with GCs in vitro and in vivo were examined. Furthermore, the mechanism by which PRP-Exos rescue the GC-induced apoptosis through the Akt/Bad/Bcl-2 pathway was also investigated. The results indicate that PRP-Exos have the capability to prevent GC-induced apoptosis in a rat model of ONFH by promoting Bcl-2 expression via the Akt/Bad/Bcl-2 signal pathway under ER stress.

Diabetic wounds, one of the most enervating complications of diabetes mellitus, affect millions of people worldwide annually. Vascular insufficiency, caused by hyperglycemia, is one of the primary causes and categories of diabetic impaired wound healing. Recently, long noncoding RNA (LncRNA)-H19, which is significantly decreased in diabetes and may be crucial in triggering angiogenesis, has attracted increasing interest. The possible relationship between the decrease of LncRNA-H19 and the impairment of angiogenesis in diabetes could involve impairment of the insulin–phosphatidylinositol 3-kinase (PI3K)–Akt pathway via the interdiction of LncRNA-H19. Thus, a therapeutic strategy utilizing LncRNA-H19 delivery is feasible. In this study, we investigated the possibility of using high-yield extracellular vesicle-mimetic nanovesicles (EMNVs) as an effective nano-drug delivery system for LncRNA, and studied the function of EMNVs with a high content of LncRNA-H19 (H19EMNVs). The results, which were exciting, showed that H19EMNVs had a strong ability to neutralize the regeneration-inhibiting effect of hyperglycemia, and could remarkably accelerate the healing processes of chronic wounds. Our results suggest that bioengineered EMNVs can serve as a powerful instrument to effectively deliver LncRNA and will be an extremely promising multifunctional drug delivery system in the immediate future.

Hydroxyapatite/chitosan composite hydrogels loaded with exosomes was fabricated for promoting wound surface re-epithelialization, angiogenesis, collagen maturity and diabetic chronic wound healing.

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High-order assembly plays a significant role in the formation of living organisms containing a large number of biomacromolecules and, thus, enlightens the construction of nanomaterials that can load macromolecular payloads at a high efficiency. Herein, by choosing anionic hyaluronic acid (HA) as a model payload, we demonstrated how the electrostatic-interaction-induced high-order assembly can be used to load efficiently biomacromolecules into complex coacervate nanodroplets. The resultant assemblies were primarily composed of HA and cationic chitosan oligosaccharide/dextran (COS/Dex) nanogels and had a controllable structure while also exhibiting biological functionality. HA in the assemblies is capable of targeting CD44-overexpressed tumor cells through CD44-mediated endocytic pathways, which are elucidated herein. Therefore, this study provides a reliable approach for the efficient loading of macromolecular payloads into complex coacervate nanodroplets via electrostatic-attraction-induced high-order assembly.

Background:Varus displaced fractures of the proximal part of the humerus, particularly in osteoporotic bone, commonly require open reduction and internal fixation. However, surgical treatment methods remain controversial and have shown inconsistent results. A fibular allograft for indirect medial reduction and strut support has been used in an effort to prevent secondary postoperative varus displacement. However, the long-term outcomes of this method require confirmation. We hypothesized that placing a fibular strut parallel to the calcar screw could increase the biomechanical stability of the medial hinge, thus preventing secondary varus deformity. In the present study, we compared the clinical outcomes of locking plate use with and without medial strut support with use of a fibular allograft for the treatment of varus humeral fractures in patients ≥65 years old.Methods:We compared 2 different graft techniques involving the use of fibular allografts in elderly patients with varus displaced proximal humeral fractures who underwent open reduction and internal fixation. The patients were divided into 3 groups: (1) the intramedullary graft group (Group A), (2) the medial hinge support group (Group B), and (3) the locking plate alone group (Group C). Clinical outcomes included the final varus angulation of the humeral head, the occurrence of major complications (screw cut-out or cut-through or osteonecrosis), and the American Shoulder and Elbow Surgeons (ASES) score at 1 year after treatment.Results:A total of 128 patients were included in our study. The final varus angles were 14.7°, 13.1°, and 18.6°, for the intramedullary graft group, the medial hinge support group, and locking plate alone group, respectively. The mean ASES scores were 87.2, 88.6, and 82.2, respectively. There were differences in ASES scores between Group A and Group C as well as also between Group B and Group C. Fewer major complications were found in patients managed with locking plates in combination with intramedullary graft or medial hinge support (Group A and Group B) than in patients managed with locking plates alone (Group C).Conclusions:The use of a locking plate in combination with medial strut support with use of a fibular allograft reduced complications when used for the treatment of varus displaced proximal humeral fractures in elderly patients in comparison with the use of a locking plate alone.Level of Evidence:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

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Aims The aim of this study was to explore why some calcar screws are malpositioned when a proximal humeral fracture is treated by internal fixation with a locking plate, and to identify risk factors for this phenomenon. Some suggestions can be made of ways to avoid this error. Methods We retrospectively identified all proximal humeral fractures treated in our institution between October 2016 and October 2018 using the hospital information system. The patients’ medical and radiological data were collected, and we divided potential risk factors into two groups: preoperative factors and intraoperative factors. Preoperative factors included age, sex, height, weight, body mass index, proximal humeral bone mineral density, type of fracture, the condition of the medial hinge, and medial metaphyseal head extension. Intraoperative factors included the grade of surgeon, neck-shaft angle after reduction, humeral head height, restoration of medial support, and quality of reduction. Adjusted binary logistic regression and multivariate logistic regression models were used to identify pre- and intraoperative risk factors. Area under the curve (AUC) analysis was used to evaluate the discriminative ability of the multivariable model. Results Data from 203 patients (63 males and 140 females) with a mean age of 62 years (22 to 89) were analyzed. In 49 fractures, the calcar screw was considered to be malpositioned; in 154 it was in the optimal position. The rate of malpositioning was therefore 24% (49/203). No preoperative risk factor was found for malpositioning of the calcar screws. Only the neck-shaft angle was found to be related to the risk of screw malpositioning in a multivariate model (with an AUC of 0.72). For the fractures in which the neck-shaft angle was reduced to between 130° and 150°, 91% (133/46) of calcar screws were in the optimal position. Conclusion The neck-shaft angle is the key factor for the appropriate positioning of calcar screws when treating a proximal humeral fracture with a locking plate. We recommend reducing the angle to between 130° and 150°. Cite this article: Bone Joint J 2020;102-B(12):1629–1635.