Mesenchymal stem cells (MSCs) and hyaluronic acid (HA) have been found in previous studies to have great potential for medical use. This study aimed to investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) combined with HA on articular cartilage repair in canines. Twenty-four healthy canines (48 knee-joints), male or female with weight ranging from 5 to 6 kg, were operated on to induce cartilage defect model and divided into 3 groups randomly which received different treatments: BMSCs plus HA (BMSCs-HA), HA alone, and saline. Twenty-eight weeks after treatment, all canines were sacrificed and analyzed by gross appearance, magnetic resonance imaging (MRI), hematoxylin-eosin (HE) staining, Masson staining, toluidine blue staining, type II collagen immunohistochemistry, gross grading scale and histological scores. MSCs plus HA regenerated more cartilage-like tissue than did HA alone or saline. According to the macroscopic evaluation and histological assessment score, treatment with MSCs plus HA also lead to significant improvement in cartilage defects compared to those in the other 2 treatment groups (P < 0.05). These findings suggested that allogeneic BMSCs plus HA rather than HA alone was effective in promoting the formation of cartilage-like tissue for repairing cartilage defect in canines.

Vascularization in bone tissues is essential for the distribution of nutrients and oxygen, as well as the removal of waste products. Fabrication of tissue-engineered bone constructs with functional vascular networks has great potential for biomimicking nature bone tissue in vitro and enhancing bone regeneration in vivo. Over the past decades, many approaches have been applied to fabricate biomimetic vascularized tissue-engineered bone constructs. However, traditional tissue-engineered methods based on seeding cells into scaffolds are unable to control the spatial architecture and the encapsulated cell distribution precisely, which posed a significant challenge in constructing complex vascularized bone tissues with precise biomimetic properties. In recent years, as a pioneering technology, three-dimensional (3D) bioprinting technology has been applied to fabricate multiscale, biomimetic, multi-cellular tissues with a highly complex tissue microenvironment through layer-by-layer printing. This review discussed the application of 3D bioprinting technology in the vascularized tissue-engineered bone fabrication, where the current status and unique challenges were critically reviewed. Furthermore, the mechanisms of vascular formation, the process of 3D bioprinting, and the current development of bioink properties were also discussed.

It is well known that stem cells reside within tissue engineering functional microenvironments that physically localize them and direct their stem cell fate. Recent efforts in the development of more complex and engineered scaffold technologies, together with new understanding of stem cell behavior in vitro, have provided a new impetus to study regulation and directing stem cell fate. A variety of tissue engineering technologies have been developed to regulate the fate of stem cells. Traditional methods to change the fate of stem cells are adding growth factors or some signaling pathways. In recent years, many studies have revealed that the geometrical microenvironment played an essential role in regulating the fate of stem cells, and the physical factors of scaffolds including mechanical properties, pore sizes, porosity, surface stiffness, three-dimensional structures, and mechanical stimulation may affect the fate of stem cells. Chemical factors such as cell-adhesive ligands and exogenous growth factors would also regulate the fate of stem cells. Understanding how these physical and chemical cues affect the fate of stem cells is essential for building more complex and controlled scaffolds for directing stem cell fate.

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Stem cell therapy is considered an optimistic approach to replace current treatments for cartilage defects. Recently, human urine-derived stem cells (hUSCs), which are isolated from the urine, are studied as a promising candidate for many tissue engineering therapies due to their multipotency and sufficient proliferation activities. However, it has not yet been reported whether hUSCs can be employed in cartilage defects. In this study, we revealed that induced hUSCs expressed chondrogenic-related proteins, including aggrecan and collagen II, and their gene expression levels were upregulated in vitro. Moreover, we combined hUSCs with hyaluronic acid (HA) and injected hUSCs-HA into a rabbit knee joint with cartilage defect. Twelve weeks after the injection, the histologic analyses (HE, toluidine blue, and Masson trichrome staining), immunohistochemistry (aggrecan and collagen II), and histologic grade of the sample indicated that hUSCs-HA could stimulate much more neocartilage formation compared with hUSCs alone, pure HA, and saline, which only induced the modest cartilage regeneration. In this study, we demonstrated that hUSCs could be a potential cell source for stem cell therapies to treat cartilage-related defects in the future.

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BackgroundElderly hip fracture (HF) patients are at very high risk of developing deep vein thrombosis (DVT), which increases their perioperative mortality. However, data focusing on the admission prevalence of DVT in elderly Chinese patients with hip fracture are limited. Venography and ultrasonography are not suitable for most elderly HF patients; there is also controversy about the prognostic value of D-dimer in elderly patients. Thus, our primary goal was to clarify the prevalence of and risk factors for DVT in elderly Chinese HF patients at admission. Our secondary goal was to evaluate the diagnostic value of a new predictor of DVT based on the risk factors for elderly HF patients.MethodsThis retrospective study was conducted in the West China Hospital, Sichuan University. Between January 2015 and January 2017, 248 elderly Chinese HF patients (> 60 years) were enrolled in this study. The subjects were diagnosed with DVT using ultrasonography or venography. All the patients’ clinical data were obtained, including demographic variables, medical history, comorbidities, and laboratory results. A stepwise multiple logistic regression analysis was used to identify the risk factors contributing to the occurrence of DVT. The value of the new DVT predictor was calculated using a formula based on the coefficient regression and independent variables. A receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of different factors.ResultsOf the study patients, 74 (29.8%) were diagnosed with DVT, including sixty-five (87.8%) with distal peripheral, five (6.8%) with proximal central and four (5.4%) with mixed DVT. A multivariate logistic regression analysis showed that five risk factors increased the occurrence of DVT at admission, including gender, age, time from injury to admission, fibrinogen, and D-dimer. The new DVT predictor was calculated using the following formula: 1.131× (female = 1, male = 0) + 0.071 × age (years) + 0.571 × time from injury to admission (days) + 1.028 × fibrinogen(g/L) + 0.123 × D-dimer(g/L). The diagnostic value of the new predictor was highest among those risk predictors whose AUC (area under the ROC curves) value was 0.852.ConclusionsThe results of this study revealed a high prevalence of DVT in elderly Chinese HF patients at admission. Moreover, the new predictor, based on risk factors, was a good method to improve the diagnosis of DVT.

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