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The repair of critical-sized calvarial defects is a challenging problem for orthopedic surgery. One of the promising strategies of bone bioengineering to enhance the efficacy of large bone defect regeneration is the combined delivery of stem cells with osteoinductive factors within polymer carriers. The purpose of the research was to study the regenerative effects of heparin-conjugated fibrin (HCF) hydrogel containing bone morphogenetic protein 2 (BMP-2) and adipose-derived pericytes (ADPs) in a rat critical-sized calvarial defect model. In vitro analysis revealed that the HCF hydrogel was able to control the BMP-2 release and induce alkaline phosphatase (ALP) activity in neonatal rat osteoblasts. In addition, it was found that eluted BMP-2 significantly induced the osteogenic differentiation of ADPs. It was characterized by the increased ALP activity, osteocalcin expression and calcium deposits in ADPs. In vivo studies have shown that both HCF hydrogel with BMP-2 and HCF hydrogel with pericytes are able to significantly increase the regeneration of critical-sized calvarial defects in comparison with the control group. Nevertheless, the greatest regenerative effect was found after the co-delivery of ADPs and BMP-2 into a critical-sized calvarial defect. Thus, our findings suggest that the combined delivery of ADPs and BMP-2 in HCF hydrogel holds promise to be applied as an alternative biopolymer for the critical-sized bone defect restoration.
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Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has had an unprecedented impact on people around the world, particularly those who were suffering from autoimmune rheumatic diseases (AIRDs). The world community acknowledges the significance of COVID-19 vaccination in patients with autoimmune disorders and emphasizes the priority of this category to receive vaccination over the general population. Although many studies have been published since the first phases of vaccination all over the world, multiple related factors still need to be further investigated. Material and methods: We investigated the COVID-19 vaccination status in patients with AIRDs, by performing a cross-sectional, interview-based study filled in by patients attending their clinics in the Astana city, capital of Kazakhstan, from April to July 2023. The survey questionnaire consisted of a set of questions, concerning patient characteristics, treatment details, accepted vaccines and characteristics of COVID-19 infection. The study objectives were to evaluate vaccine hesitancy, adverse effects, breakthrough infections and flare of underlying rheumatic disease in this population subgroup. Results: There were 193 participants, with a median age of 50.3 ±12.9 years. Among them, 62 (32.1%) were vaccinated with at least single dose of vaccine, 16 (25.8%) of whom were fully vaccinated. The commonest (89; 68%) reason for vaccine hesitancy was a fear of autoimmune disease worsening. Vaccine-related adverse effects (AEs) were reported by 66.7% of patients. We found that vaccination provoked AIRD exacerbation in 19% of patients with AEs. Eight patients reported flare of pre-existing rheumatic disease after vaccination. The incidence of breakthrough infections was similar in the groups of vaccinated individuals (n = 12), 12.9% of whom were partially and 6.5% fully vaccinated. Conclusions: The vaccination was found to be safe in patients with rheumatic diseases. Fear of autoimmune status was the major reason for vaccine reluctance. All reported adverse events were minor. The minority subgroup within the sample had subsequent breakthrough infections or autoimmune disease flare-ups.
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Pericytes, as perivascular cells, are present in all vascularized organs and tissues, and they actively interact with endothelial cells in capillaries and microvessels. Their involvement includes functions like blood pressure regulation, tissue regeneration, and scarring. Studies have confirmed that pericytes play a crucial role in bone tissue regeneration through direct osteodifferentiation processes, paracrine actions, and vascularization. Recent preclinical and clinical experiments have shown that combining perivascular cells with osteogenic factors and tissue-engineered scaffolds can be therapeutically effective in restoring bone defects. This approach holds promise for addressing bone-related medical conditions. In this review, we have emphasized the characteristics of pericytes and their involvement in angiogenesis and osteogenesis. Furthermore, we have explored recent advancements in the use of pericytes in preclinical and clinical investigations, indicating their potential as a therapeutic resource in clinical applications.