A combinatorial cell-laden gel microarray for inducing osteogenic differentiation of human mesenchymal stem cells

Development of three dimensional (3D) microenvironments that direct stem cell differentiation into functional cell types remains a major challenge in the field of regenerative medicine. Here, we describe a new platform to address this challenge by utilizing a robotic microarray spotter for testing stem cell fates inside various miniaturized cell-laden gels in a systematic manner. To demonstrate the feasibility of our platform, we evaluated the osteogenic differentiation of human mesenchymal stem cells (hMSCs) within combinatorial 3D niches. We were able to identify specific combinations, that enhanced the expression of osteogenic markers. Notably, these ‘hit' combinations directed hMSCs to form mineralized tissue when conditions were translated to 3D macroscale hydrogels, indicating that the miniaturization of the experimental system did not alter stem cell fate. Overall, our findings confirmed that the 3D cell-laden gel microarray can be used for screening of different conditions in a rapid, cost-effective, and multiplexed manner for a broad range of tissue engineering applications

Bone mineral density status in patients with recent-onset rheumatoid arthritis

Background: Osteoporosis is a sizable comorbidity complication in Rheumatoid Arthritis (RA) sufferers. In the current study, the prevalence of osteopenia and osteoporosis in active RA sufferers and the association of disease-related factors of osteoporosis and reduced bone mineral density (BMD) have been examined. Methods: In this cross-sectional study, 300 new-onset symptoms (less than one year) RA patients without a history of glucocorticoids or DMARDs were selected. Biochemical blood measurements and BMD status were performed with dual-energy X-ray absorptiometry. According to the T-scores of the patients, they were divided into three groups: osteoporosis<-2.5, -2.5 < osteopenia <-1, and − 1 < normal. Also, the MDHAQ questionnaire, DAS-28, and FRAX criteria were calculated for all patients. Multivariate logistic regression was used to determine the associated factors of osteoporosis and osteopenia. Results: The Prevalence of osteoporosis and osteopenia was 27% (95%CI:22–32) and 45% (95%CI:39–51), respectively. The multivariate regression analysis showed that age could play a role as an associated factor for spine/hip Osteoporosis and Osteopenia. The female gender is also a predictor of Spine osteopenia Patients with Total hip Osteoporosis were more likely to have higher DAS-28 (OR 1.86, CI 1.16–3.14) and positive CRP (OR 11.42, CI 2.65–63.26). Conclusion: recent-onset RA patients are at risk for osteoporosis and its complications, regardless of using glucocorticoids or DMARDs. Demographic factors (e.g. age and female gender), patients’ MDHAQ scores, and disease-related factors(e.g., DAS-28, positive CRP were associated with reduced BMD levels. Therefore, it is recommended that clinicians investigate early BMD measurements to have a reasonable judgment for further interventions. © 2023, The Author(s), under exclusive licence to Tehran University of Medical Sciences

Thin Polymer Brush Decouples Biomaterial's Micro-/Nano-Topology and Stem Cell Adhesion

Surface morphology and chemistry of polymers used as biomaterials, such as tissue engineering scaffolds, have a strong influence on the adhesion and behavior of human mesenchymal stem cells. Here we studied semicrystalline poly(ε-caprolactone) (PCL) substrate scaffolds, which exhibited a variation of surface morphologies and roughness originating from different spherulitic superstructures. Different substrates were obtained by varying the parameters of the thermal processing, i.e. crystallization conditions. The cells attached to these polymer substrates adopted different morphologies responding to variations in spherulite density and size. In order to decouple substrate topology effects on the cells, sub-100 nm bio-adhesive polymer brush coatings of oligo(ethylene glycol) methacrylates were grafted from PCL and functionalized with fibronectin. On surfaces featuring different surface textures, dense and sub-100 nm thick brush coatings determined the response of cells, irrespective to the underlying topology. Thus, polymer brushes decouple substrate micro-/nano-topology and the adhesion of stem cells

Quantitative mechanistic model reveals key determinants of placental IgG transfer and informs prenatal immunization strategies.

Transplacental antibody transfer is crucially important in shaping neonatal immunity. Recently, prenatal maternal immunization has been employed to boost pathogen-specific immunoglobulin G (IgG) transfer to the fetus. Multiple factors have been implicated in antibody transfer, but how these key regulators work together to elicit selective transfer is pertinent to engineering vaccines for mothers to optimally immunize their newborns. Here, we present the first quantitative mechanistic model to uncover the determinants of placental antibody transfer and inform personalized immunization approaches. We identified placental FcγRIIb expressed by endothelial cells as a limiting factor in receptor-mediated transfer, which plays a key role in promoting preferential transport of subclasses IgG1, IgG3, and IgG4, but not IgG2. Integrated computational modeling and in vitro experiments reveal that IgG subclass abundance, Fc receptor (FcR) binding affinity, and FcR abundance in syncytiotrophoblasts and endothelial cells contribute to inter-subclass competition and potentially inter- and intra-patient antibody transfer heterogeneity. We developed an in silico prenatal vaccine testbed by combining a computational model of maternal vaccination with this placental transfer model using the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine as a case study. Model simulations unveiled precision prenatal immunization opportunities that account for a patient's anticipated gestational length, placental size, and FcR expression by modulating vaccine timing, dosage, and adjuvant. This computational approach provides new perspectives on the dynamics of maternal-fetal antibody transfer in humans and potential avenues to optimize prenatal vaccinations that promote neonatal immunity

A PSO-DP Based Method to Determination of the Optimal Number, Location, and Size of FACTS Devices in Power Systems

The presence of reactive component of current in transmission lines causes adverse impact on the network, including power losses, reduction of line capacity, and voltage drop. These adverse impacts can be reduced by using the first or second generation of FACTS devices. In this paper, these adverse impacts can be reduced optimally by using one of the modern optimization techniques, i.e., particle swarm optimization algorithm (PSO algorithm). By using this algorithm, the optimal size of the static VAr compensator (FACTS devices) in a 30 bus IEEE test system is determined. At first, the load flow equations of the 30 bus IEEE test system is defined in the MATLAB software by means of dynamic programming method, and the number of SVCs will be determined by using the system sensitivity function (power losses and the sum of buses voltage drop square); then, the optimal sizes of the FACTS devices is obtained by means of PSO algorithm

Fundamental properties of smart hydrogels for tissue engineering applications:A review

Tissue engineering is an advanced and potential biomedical approach to treat patients suffering from lost or failed an organ or tissue to repair and regenerate damaged tissues that increase life expectancy. The biopolymers have been used to fabricate smart hydrogels to repair damaged tissue as they imitate the extracellular matrix (ECM) with intricate structural and functional characteristics. These hydrogels offer desired and controllable qualities, such as tunable mechanical stiffness and strength, inherent adaptability and biocompatibility, swellability, and biodegradability, all crucial for tissue engineering. Smart hydrogels provide a superior cellular environment for tissue engineering, enabling the generation of cutting-edge synthetic tissues due to their special qualities, such as stimuli sensitivity and reactivity. Numerous review articles have presented the exceptional potential of hydrogels for various biomedical applications, including drug delivery, regenerative medicine, and tissue engineering. Still, it is essential to write a comprehensive review article on smart hydrogels that successfully addresses the essential challenging issues in tissue engineering. Hence, the recent development on smart hydrogel for state-of-the-art tissue engineering conferred progress, highlighting significant challenges and future perspectives. This review discusses recent advances in smart hydrogels fabricated from biological macromolecules and their use for advanced tissue engineering. It also provides critical insight, emphasizing future research directions and progress in tissue engineering.</p

3D cell-laden polymers to release bioactive products in the eye.

Millions of people worldwide suffer from debilitating, progressive, and often permanent loss of vision without any viable treatment options. The complex physiological barriers of the eye contribute to the difficulty in developing novel therapies by limiting our ability to deliver therapeutics in a sustained and controlled manner; especially when attempting to deliver drugs to the posterior eye or trying to regenerate the diseased retina. Cell-based therapies offer a significant potential advancement in these situations. In particular, encapsulating, or immunoisolating, cells within implantable, semi-permeable membranes has emerged as a clinically viable means of delivering therapeutic molecules to the eye for indefinite periods of time. The optimization of encapsulation device designs is occurring together with refinements in biomaterials, genetic engineering, and stem-cell production, yielding, for the first time, the possibility of widespread therapeutic use of this technology. Here, we highlight the status of the most advanced and widely explored iteration of cell encapsulation with an eye toward translating the potential of this technological approach to the medical reality