Osteonecrosis of the femoral head (ONFH) is a disabling disease characterized by the disruption of the blood supply to the femoral head, leading to the apoptosis and necrosis of bone cells and subsequent joint collapse. Total hip arthroplasty is not optimal since most patients are young. Multiple risk factors contribute to osteonecrosis, including glucocorticoid (GC) usage, excessive alcohol intake, hypercholesterolemia, and smoking. Continuous stimulation by many variables causes a chronic inflammatory milieu, with clinical repercussions including endothelial dysfunction, leading to thrombosis, coagulopathy, and poor angiogenesis. Immune cells are the primary regulators of inflammation. Innate and adaptive immune cells interact with endothelial cells to hinder the regeneration and repair of bone lesions. An in-depth examination of the pathological drivers of ONFH reveals that endothelial dysfunction may be a major cause of osteonecrosis. Understanding the involvement of endothelial dysfunction in the chronic inflammation of osteonecrosis could aid in the development of possible therapies. This review summarizes the role of endothelial cells in osteonecrosis and further explains the pathophysiological mechanism of endothelial dysfunction in this disease from the perspective of inflammation to provide new ideas for the treatment of osteonecrosis.

Avascular necrosis of the femoral head (ANFH) is a type of osteonecrosis due to the cessation of blood supply, characterized by persistent local pain and collapse of the joint. The etiology of ANFH is multifaceted, and while its precise pathogenesis remains elusive, it is currently widely believed that the femoral head is highly dependent on the vascular system. A large number of studies have shown that vascular injury is the initial factor in the onset of ANFH. In this review, we briefly introduced the process of angiogenesis and the blood supply to the femoral head, with a focus on summarizing the existing research on promoting angiogenesis for the treatment of ANFH. We conclude that providing alternative pathways through angiogenesis to resolve the problem of the obstructed free flow of the blood is an important means of treating ANFH. Moreover, we also looked forward to the mechanism of endothelial metabolism, which has not yet been studied in femoral head necrosis models, providing potential strategies for more effective use of angiogenesis for the treatment of femoral head necrosis.

Endothelial impairment and dysfunction are closely related to the pathogenesis of steroid-associated osteonecrosis of the femoral head (SONFH). Recent studies have showed that hypoxia inducible factor-1α (HIF-1α) plays a crucial role in endothelial homeostasis maintenance. Dimethyloxalylglycine (DMOG) could suppress HIF-1 degradation and result in nucleus stabilization by repressing prolyl hydroxylase domain (PHD) enzymatic activity. Our results showed that methylprednisolone (MPS) remarkably undermined biological function of endothelial progenitor cells (EPC) by inhibiting colony formation, migration, angiogenesis, and stimulating senescence of EPCs, while DMOG treatment alleviated these effects by promoting HIF-1α signaling pathway, as evidenced by senescence-associated β-galactosidase (SA-β-Gal) staining, colony-forming unit, matrigel tube formation, and transwell assays. The levels of proteins related to angiogenesis were determined by ELISA and Western blotting. In addition, active HIF-1α bolstered the targeting and homing of endogenous EPCs to the injured endothelium in the femoral head. Histopathologically, our in vivo study showed that DMOG not only alleviated glucocorticoid-induced osteonecrosis but also promoted angiogenesis and osteogenesis in the femoral head as detected by microcomputed tomography (Micro-CT) analysis and histological staining of OCN, TRAP, and Factor Ⅷ. However, all of these effects were impaired by an HIF-1α inhibitor. These findings demonstrate that targeting HIF-1α in EPCs may constitute a novel therapeutic approach for the treatment of SONFH.

Summary: Background: The outbreak of coronavirus disease 2019 (COVID-19) has become a world-wide emergency. Fangcang shelter hospitals have been applied in COVID-19 to ease ongoing shortage of medical resources in Wuhan since February 2020. Method: This study enrolled all cases (no=1848) with mild or moderate type of COVID-19 in Fangcang shelter hospital of Jianghan in Wuhan from Feb 5th to Mar 9th, 2020. Diagnosis of COVID-19 was based on the National health commission of China. Epidemiological history, comorbidity, vital signs, symptoms and signs were recorded in detail. Laboratory tests included biochemical indicators and nucleic acid tests by throat swabs have been performed as well. Finding: A total of 1327 patients reached the criteria of isolation release. Meanwhile, 521 patients have been transferred to the designated hospitals for further treatment, including severe type, fever more than 3 days, and severe comorbidity. The case-severity rate (rate of mild or moderate type transforming to severe type) was 3.0% in the shelter hospital. The patients from mild or moderate type to severe type showed the following clinical characteristics: the median incubation (onset to shelter) period was 10 days; they were all symptomatic at admission; fever, cough, and fatigue were the most common symptoms; hypertension, diabetes and coronary heart diseases were common co-morbidities; most of the patients had elevated levels of CRP at ill onset with 33.3% over 10 mg per L; bilateral distribution and ground-glass opacity were the most common manifestations in chest CT. Interpretation: The potential risk factors of fever, fatigue, high level of C-reactive protein were the risk factors to identify the progression of COVID-19 patients with mild or moderate type. Fangcang shelter hospitals have substantially reduced the time from the onset of severe symptoms transfer to a designated hospital. Early application of the Fangcang shelter hospital may contribute to decrease the ratio of mild transforming to severe patients. Funding: No specific grant from any funding was applied to this research. Research in context: Evidence before this study: We searched PubMed from Nov 1, 2019, to Apr 8, 2020, for studies published in any language using the terms “COVID-19”, “coronavirus disease 2019”, “novel coronavirus”, “cabin hospital”, “shelter hospital”. Five studies have been found about coronavirus disease 2019 (COVID-19) in shelter hospital or cabin hospital. Fangcang shelter hospital of Jianghan received the largest number of patients among Fangcang shelter hospitals in Wuhan. These studies were related to development of Fangcang shelter hospitals, explaining three key characteristics (rapid construction, massive scale, and low cost) and five essential functions (isolation, triage, basic medical care, frequent monitoring and rapid referral, and essential living and social engagement). To our knowledge, there are no studies to comprehensively investigate a cohort of mild COVID-19 patients transfer to designated hospital from shelter hospital and their distinctive clinical features. Since Fangcang shelter hospital is a novel public health strategy, we aimed to investigate the clinical characteristics and risk factors for developed COVID-19 patients transfer to the designated hospital in Jianghan Fangcang shelter Hospital. Added value of this study: From Feb 5th to Mar 9th, a total of 1848 cases of mild or moderate type of COVID-19 were enrolled in Fangcang shelter hospital of Jianghan (Wuhan, China). Of these cases, 521 patients were transferred to designated hospitals. Rate of mild or moderate type transforming to severe type was 3.0 % (56/1848) in the Fangcang shelter hospital. The median incubation (onset to shelter) period was 10 days (IQR 8.0-16.0). Patients with fever on cabin admission, high level C-reactive protein were also associated with mild-to-severe. Early application of the shelter hospital may contribute to alleviate the shortage of medical resources and decrease the ratio of severe patients. Furthermore, Fangcang shelter hospitals are likely to have substantially reduced the time from the onset of severe symptoms to admission to a designated hospital. The clinical characteristics of patients transferred to the designated hospital were important for the revision of admission criteria of COVID patients in Fangcang shelter hospitals. Dynamic observation the risk factors of mild to severe patients is contribute to great value for early prognosis and treatment. Implications of all the available evidence: Keep vigilance of those mild patients whose had a fever over 38.0°C, cough and fatigue when they isolated at home. Fangcang shelter hospital could provide the rational strategy for isolation and triage of infected patients and decrease the family or community transmission cases.

Osteonecrosis of the femoral head (ONFH) is a devastating ischemic bone disease. Its pathogenesis is multifactorial, including impaired bone remodeling, chronic inflammation, dysregulated lipid metabolism, and bone marrow edema, all intrinsically linked to vascular dysfunction. However, conventional experimental models fail to fully capture the complex pathophysiology of ONFH. Animal models suffer from interspecies differences and are inherently limited in investigating bone marrow edema and femoral head collapse. Therefore, the complex pathogenesis of ONFH remains poorly understood due to the limitations of existing models. Recently, organoids have emerged as a powerful tool for complex and biomimetic disease modeling, with vascularization strategies developed to enhance their structural and functional maturity. The central role of vascular dysfunction in ONFH underscores the value of vascularized bone organoids (VBOs) as a biomimetic model. In this review, we summarize vascularization strategies for bone organoids, including in vitro approaches, in vivo integration, and bioengineering technologies. For ONFH, VBOs provide an advanced experimental model for elucidating disrupted angiogenesis–osteogenesis coupling, inter-tissue crosstalk, and alterations in intraosseous pressure. VBOs also hold significant value for evaluating pro-angiogenic therapies, advancing regenerative medicine, and guiding personalized treatment. Overall, VBOs offer a promising platform for advancing mechanistic insights and therapeutic development in ONFH.