Direct-to-Patient Mobile Teledermoscopy: Prospective Observational Study.

Direct-to-patient mobile teledermoscopy is a feasible and useful adjunct to smartphone imaging for monitoring patient-identified lesions of concern, achieving comparable diagnostic and management accuracy as in-office dermatology.

The cost-effectiveness of a bedaquiline-containing short-course regimen for the treatment of multidrug-resistant tuberculosis in South Africa.

Background: Bedaquiline-containing regimens have demonstrated improved outcomes over injectable-containing regimens in the long-term treatment of multidrug-resistant tuberculosis (MDR-TB). Recently, the World Health Organization (WHO) recommended replacing injectables in the standard short-course regimen (SCR) with a bedaquiline-containing regimen. The South African national TB program similarly recommends a bedaquiline-containing regimen. Here, we investigated the cost-effectiveness of a bedaquiline-containing SCR versus an injectable-containing SCR for the treatment of MDR-TB in South Africa.Methods: A Markov model was adapted to simulate the incidence of active patients with MDR-TB. Patients could transition through eight health states: active MDR-TB, culture conversion, cure, follow-up loss, secondary MDR-TB, extensively DR-TB, end-of-life care, and death. A 5% discount was assumed on costs and outcomes. Health outcomes were expressed as disability-adjusted life years (DALYs).Results: Over a 10-year time horizon, a bedaquiline-containing SCR dominated an injectable-containing SCR, with an incremental saving of US $982 per DALY averted. A bedaquiline-containing SCR was associated with lower total costs versus an injectable-containing SCR (US $597 versus $657 million), of which US $3.2 versus $21.9 million was attributed to adverse event management.Conclusions: Replacing an injectable-containing SCR with a bedaquiline-containing SCR is cost-effective, offering a cost-saving alternative with improved patient outcomes for MDR-TB.

Early Vascular Cells Improve Microvascularization Within 3D Cardiac Spheroids.

Introduction: A key obstacle in the creation of engineered cardiac tissues of clinically relevant sizes is limited diffusion of oxygen and nutrients. Thus, there is a need for organized vascularization within a three-dimensional (3D) tissue environment. Human induced pluripotent stem cell (hiPSC)-derived early vascular cells (EVCs) have shown to improve organization of vascular networks within hydrogels. We hypothesize that introduction of EVCs into 3D microtissue spheroids will lead to increased microvascular formation and improve spheroid formation. Methods: HiPSC-derived cardiomyocytes (CMs) were cocultured with human adult ventricular cardiac fibroblasts (FB) and either human umbilical vein endothelial cells (HUVECs) or hiPSC-derived EVCs for 72 h to form mixed cell spheroids. Three different groups of cell ratios were tested: Group 1 (control) consisted of CM:FB:HUVEC 70:15:15, Group 2 consisted of CM:FB:EVC 70:15:15, and Group 3 consisted of CM:FB:EVC 40:15:45. Vascularization, cell distribution, and cardiac function were investigated. Results: Improved microvasculature was found in EVC spheroids with new morphologies of endothelial organization not found in Group 1 spheroids. CMs were found in a core-shell type distribution in Group 1 spheroids, but more uniformly distributed in EVC spheroids. Contraction rate increased into Group 2 spheroids compared to Group 1 spheroids. Conclusion: The triculture of CM, FB, and EVC within a multicellular cardiac spheroid promotes microvascular formation and cardiac spheroid contraction.

Different degradation rates of nanofiber vascular grafts in small and large animal models.

Nanofiber vascular grafts have been shown to create neovessels made of autologous tissue, by in vivo scaffold biodegradation over time. However, many studies on graft materials and biodegradation have been conducted in vitro or in small animal models, instead of large animal models, which demonstrate different degradation profiles. In this study, we compared the degradation profiles of nanofiber vascular grafts in a rat model and a sheep model, while controlling for the type of graft material, the duration of implantation, fabrication method, type of circulation (arterial/venous), and type of surgery (interposition graft). We found that there was significantly less remaining scaffold (i.e., faster degradation) in nanofiber vascular grafts implanted in the sheep model compared with the rat model, in both the arterial and the venous circulations, at 6 months postimplantation. In addition, there was more extracellular matrix deposition, more elastin formation, more mature collagen, and no calcification in the sheep model compared with the rat model. In conclusion, studies comparing degradation of vascular grafts in large and small animal models remain limited. For clinical translation of nanofiber vascular grafts, it is important to understand these differences.

Cardiac regeneration using human-induced pluripotent stem cell-derived biomaterial-free 3D-bioprinted cardiac patch in vivo.

One of the leading causes of death worldwide is heart failure. Despite advances in the treatment and prevention of heart failure, the number of affected patients continues to increase. We have recently developed 3D-bioprinted biomaterial-free cardiac tissue that has the potential to improve cardiac function. This study aims to evaluate the in vivo regenerative potential of these 3D-bioprinted cardiac patches. The cardiac patches were generated using 3D-bioprinting technology in conjunction with cellular spheroids created from a coculture of human-induced pluripotent stem cell-derived cardiomyocytes, fibroblasts, and endothelial cells. Once printed and cultured, the cardiac patches were implanted into a rat myocardial infarction model (n = 6). A control group (n = 6) without the implantation of cardiac tissue patches was used for comparison. The potential for regeneration was measured 4 weeks after the surgery with histology and echocardiography. 4 weeks after surgery, the survival rates were 100% and 83% in the experimental and the control group, respectively. In the cardiac patch group, the average vessel counts within the infarcted area were higher than those within the control group. The scar area in the cardiac patch group was significantly smaller than that in the control group. (Figure S1) Echocardiography showed a trend of improvement of cardiac function for the experimental group, and this trend correlated with increased patch production of extracellular vesicles. 3D-bioprinted cardiac patches have the potential to improve the regeneration of cardiac tissue and promote angiogenesis in the infarcted tissues and reduce the scar tissue formation.

In vivo therapeutic applications of cell spheroids.

Spheroids are increasingly being employed to answer a wide range of clinical and biomedical inquiries ranging from pharmacology to disease pathophysiology, with the ultimate goal of using spheroids for tissue engineering and regeneration. When compared to traditional two-dimensional cell culture, spheroids have the advantage of better replicating the 3D extracellular microenvironment and its associated growth factors and signaling cascades. As knowledge about the preparation and maintenance of spheroids has improved, there has been a plethora of translational experiments investigating in vivo implantation of spheroids into various animal models studying tissue regeneration. We review methods for spheroid delivery and how they have been utilized in tissue engineering experiments. We break down efforts in this field by organ systems, discussing applications of spheroids to various animal models of disease processes and their potential clinical implications. These breakthroughs have been made possible by advancements in spheroid formation, in vivo delivery and assessment. There is unexplored potential and room for further research and development in spheroid-based tissue engineering approaches. Regenerative medicine and other clinical applications ensure this exciting area of research remains relevant for patient care.

3D bioprinting using stem cells.

Recent advances have allowed for three-dimensional (3D) printing technologies to be applied to biocompatible materials, cells and supporting components, creating a field of 3D bioprinting that holds great promise for artificial organ printing and regenerative medicine. At the same time, stem cells, such as human induced pluripotent stem cells, have driven a paradigm shift in tissue regeneration and the modeling of human disease, and represent an unlimited cell source for tissue regeneration and the study of human disease. The ability to reprogram patient-specific cells holds the promise of an enhanced understanding of disease mechanisms and phenotypic variability. 3D bioprinting has been successfully performed using multiple stem cell types of different lineages and potency. The type of 3D bioprinting employed ranged from microextrusion bioprinting, inkjet bioprinting, laser-assisted bioprinting, to newer technologies such as scaffold-free spheroid-based bioprinting. This review discusses the current advances, applications, limitations and future of 3D bioprinting using stem cells, by organ systems.

Mammalian Cell Division in 3D Matrices via Quantitative Confocal Reflection Microscopy.

The study of how mammalian cell division is regulated in a 3D environment remains largely unexplored despite its physiological relevance and therapeutic significance. Possible reasons for the lack of exploration are the experimental limitations and technical challenges that render the study of cell division in 3D culture inefficient. Here, we describe an imaging-based method to efficiently study mammalian cell division and cell-matrix interactions in 3D collagen matrices. Cells labeled with fluorescent H2B are synchronized using the combination of thymidine blocking and nocodazole treatment, followed by a mechanical shake-off technique. Synchronized cells are then embedded into a 3D collagen matrix. Cell division is monitored using live-cell microscopy. The deformation of collagen fibers during and after cell division, which is an indicator of cell-matrix interaction, can be monitored and quantified using quantitative confocal reflection microscopy. The method provides an efficient and general approach to study mammalian cell division and cell-matrix interactions in a physiologically relevant 3D environment. This approach not only provides novel insights into the molecular basis of the development of normal tissue and diseases, but also allows for the design of novel diagnostic and therapeutic approaches.