Decellularized Articular Cartilage Microgels as Microcarriers for Expansion of Mesenchymal Stem Cells

Conventional microcarriers used for expansion of human mesenchymal stem cells (hMSCs) require detachment and separation of the cells from the carrier prior to use in clinical applications for regeneration of articular cartilage, and the carrier can cause undesirable phenotypic changes in the expanded cells. This work describes a novel approach to expand hMSCs on biomimetic carriers based on adult or fetal decellularized bovine articular cartilage that supports tissue regeneration without the need to detach the expanded cells from the carrier. In this approach, the fetal or adult bovine articular cartilage was minced, decellularized, freeze-dried, ground, and sieved to produce articular cartilage microgels (CMGs) in a specified size range. Next, the hMSCs were expanded on CMGs in a bioreactor in basal medium to generate hMSC-loaded CMG microgels (CMG-MSCs). Then, the CMG-MSCs were suspended in sodium alginate, injected in a mold, crosslinked with calcium chloride, and incubated in chondrogenic medium as an injectable cellular construct for regeneration of articular cartilage. The expression of chondrogenic markers and compressive moduli of the injectable CMG-MSCs/alginate hydrogels incubated in chondrogenic medium were higher compared to the hMSCs directly encapsulated in alginate hydrogels.</jats:p

Decellularized Articular Cartilage Microgels as Microcarriers for Expansion of Mesenchymal Stem Cells

Conventional microcarriers used for expansion of human mesenchymal stem cells (hMSCs) require detachment and separation of the cells from the carrier prior to use in clinical applications for regeneration of articular cartilage, and the carrier can cause undesirable phenotypic changes in the expanded cells. This work describes a novel approach to expand hMSCs on biomimetic carriers based on adult or fetal decellularized bovine articular cartilage that supports tissue regeneration without the need to detach the expanded cells from the carrier. In this approach, the fetal or adult bovine articular cartilage was minced, decellularized, freeze-dried, ground, and sieved to produce articular cartilage microgels (CMGs) in a specified size range. Next, the hMSCs were expanded on CMGs in a bioreactor in basal medium to generate hMSC-loaded CMG microgels (CMG-MSCs). Then, the CMG-MSCs were suspended in sodium alginate, injected in a mold, crosslinked with calcium chloride, and incubated in chondrogenic medium as an injectable cellular construct for regeneration of articular cartilage. The expression of chondrogenic markers and compressive moduli of the injectable CMG-MSCs/alginate hydrogels incubated in chondrogenic medium were higher compared to the hMSCs directly encapsulated in alginate hydrogels

Hydrogel-Based Formulations for Drug Delivery to the Posterior Segment of the Eye

Hydrogel-based formulations hold significant promise for treating ocular diseases that impact the posterior segment of the eye. These formulations exhibit the ability to surmount ocular barriers and offer sustained drug release, rendering them efficacious drug delivery systems. This article addresses the challenges linked to treating disorders affecting the posterior eye segment and underscores the imperative for less invasive drug delivery methodologies. We further delve into diverse contemporary ocular dosage forms, encompassing gels, nanostructures, and implants, with a specific emphasis on hydrogels. Hydrogels offer several merits, including precise targeting, sustained release, enhanced bioavailability, and non-invasiveness. Moreover, they curtail the risk of adverse effects and foster patient adherence. An enthralling advancement is the amalgamation of hybrid drug delivery systems, integrating nanoparticles, liposomes, dendrimers, and stimuli-activated nano-systems, with hydrogels for posterior eye ailment treatment. These hybrid nano-systems exhibit promise in enhancing drug stability, prolonging drug release, and pinpointing specific tissues within the posterior segment. We also provide an overview of ongoing clinical trials and approved hydrogel-based drug delivery systems, like Retisert and Ozurdex. These systems have demonstrated efficacy in managing chronic non-infectious uveitis, Age-related Macular Degeneration (AMD), and diabetic macular edema. Nevertheless, challenges persist, including optimizing bioavailability, maintaining drug stability, and implementing personalized treatment approaches. The incessant evolution of gel-based drug delivery systems stands to substantially enhance patients&rsquo; quality of life and establish new benchmarks in treating posterior eye diseases. The future of ophthalmology brims with excitement, as gel-based drug delivery systems hold the potential to revolutionize ocular therapies, providing effective remedies for an array of vision-related afflictions

Decellularized Articular Cartilage Microparticles for Expansion of Mesenchymal Stem Cells and Zonal Regeneration of Articular Cartilage

AbstractIntroductionThe objective was to create multilayer cellular constructs using fetal or adult, decellularized articular cartilage in particulate form as microcarriers for expansion and fusion of mesenchymal stem cells (MSCs) to regenerate the stratified structure of articular cartilage.MethodsPorous microparticles (CMPs) generated from decellularized fetal or adult bovine articular cartilage were used as microcarriers for expansion of human MSCs. The CMP expanded MSCs (CMP-MSCs) were used to generate injectable hydrogels or preformed multilayer constructs for articular cartilage regeneration. In the injectable approach, CMP-MSCs were suspended in alginate gel, crosslinked with calcium chloride, and incubated in chondrogenic medium to generate an injectable regenerative construct. In the preformed approach, fetal or adult CMP-MSCs were suspended in a culture medium, allowed to settle sequentially by the force of gravity, and fused by incubation in chondrogenic medium to generate multilayer cell sheets. The constructs were characterized with respect to compressive modulus, cellularity, and expression of chondrogenic markers.ResultsHuman MSCs expanded on fetal or adult CMPs in basal medium maintained the expression of mesenchymal markers. The injectable CMP-MSCs hydrogels had significantly higher expression of chondrogenic markers and compressive modulus after four weeks incubation in chondrogenic medium compared to MSCs directly encapsulated in alginate gel; preformed CMP-MSCs cell sheets had significantly higher compressive modulus and expression of chondrogenic markers compared to MSCs in the pellet culture.ConclusionThe preformed cell sheet approach is potentially useful for creating multilayer constructs by sequential gravitational settling of CMP-MSCs to mimic the stratified structure of articular cartilage.Insight, Innovation, IntegrationThis work described a novel approach to recreate the zonal structure of articular cartilage. Human MSCs were expanded on porous microcarrier beads generated from decellularized fetal or adult bovine articular cartilage. The cell-seeded microbeads were fused by gravitational settling to form mono- or bi-layer cell sheets. The cell sheets were cultured in chondrogenic medium to regenerate the articular cartilage tissue. The in vitro regenerated tissue had higher compressive modulus and expression of chondrogenic markers compared to the MSC pellet culture.</jats:sec

COVID-19: insights into virus–receptor interactions

AbstractThe recent outbreak of Coronavirus Disease 2019 (COVID-19) calls for rapid mobilization of scientists to probe and explore solutions to this deadly disease. A limited understanding of the high transmissibility of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) relative to other coronavirus strains guides a deeper investigation into the virus/receptor interactions. The cutting-edge studies in thermodynamic and kinetic properties of interactions such as protein-protein interplays have been reviewed in many modeling and analysis studies. Highlighting the thermodynamic assessments of biological interactions and emphasizing the boosted transmissibility of SARS-CoV-2 despite its high similarity in structure and sequence with other coronavirus strains is an important and highly valuable investigation that can lead scientists to discover analytical and fundamental approaches in studying virus’s interactions. Accordingly, we have attempted to describe the crucial factors such as conformational changes and hydrophobicity particularities that influence on thermodynamic potentials in the SARS-COV-2 S-protein adsorption process. Discussing the thermodynamic potentials and the kinetics of the SARS-CoV-2 S-protein in its interaction with the ACE2 receptors of the host cell is a fundamental approach that would be extremely valuable in designing candidate pharmaceutical agents or exploring alternative treatments.</jats:p