Collagen scaffold anisotropy and static tension maintain human tendon cell phenotype in culture.

Biophysical in nature signals, due to their simplicity in implementation, are at the forefront of research and innovation to control tendon cell function in vitro. In this work, we first assessed the influence of substrate rigidity and surface topography on human tendon cells using differentially crosslinked planar and grooved collagen scaffolds. We identified the 0.

Assessing the Potential of Caprine Collagen Type I in the Development of Medical Devices.

We isolated collagen I from caprine, porcine, and bovine skin and tendon tissues and assessed their purity and chemical properties. We fabricated non-cross-linked and cross-linked scaffolds from each collagen I preparation and assessed their physicochemical and biological properties. Purity and chemical analyses did not reveal any notable differences between the groups.

The Effects of the Pneumonia Lung Microenvironment on MSC Function.

Background: Despite promise in preclinical models of acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC) have failed to translate to therapeutic benefit in clinical trials. The MSC is a live cell medicine and interacts with the patient's disease state. Here, we explored this interaction, seeking to devise strategies to enhance MSC therapeutic function.

Nebulised mesenchymal stem cell derived extracellular vesicles ameliorate E. coli induced pneumonia in a rodent model.

Background: Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) have been proposed as an alternative to cell therapy, creating new possible delivery modalities such as nebulisation. We wished to investigate the therapeutic potential of directly nebulised MSC-EVs in the mitigation of Escherichia coli-induced pneumonia.

Methods: EV size, surface markers and miRNA content were assessed pre- and post-nebulisation.

Development of three-layer collagen scaffolds to spatially direct tissue-specific cell differentiation for enthesis repair.

Enthesis repair remains a challenging clinical indication. Herein, a three-layer scaffold composed of a tendon-like layer of collagen type I, a fibrocartilage-like layer of collagen type II and a bone-like layer of collagen type I and hydroxyapatite, was designed to recapitulate the matrix composition of the enthesis. To aid tenogenic and fibrochondrogenic differentiation, bioactive molecules were loaded in the tendon-like layer or the fibrocartilage-like layer and their effect was assessed in setting using human bone marrow derived mesenchymal stromal cells and in an model.

Driving Hierarchical Collagen Fiber Formation for Functional Tendon, Ligament, and Meniscus Replacement.

Hierarchical collagen fibers are the primary source of strength in musculoskeletal tendons, ligaments, and menisci. It has remained a challenge to develop these large fibers in engineered replacements or in vivo after injury. The objective of this study was to investigate the ability of restrained cell-seeded high density collagen gels to drive hierarchical fiber formation for multiple musculoskeletal tissues.

The Few Who Made It: Commercially and Clinically Successful Innovative Bone Grafts.

Bone reconstruction techniques are mainly based on the use of tissue grafts and artificial scaffolds. The former presents well-known limitations, such as restricted graft availability and donor site morbidity, while the latter commonly results in poor graft integration and fixation in the bone, which leads to the unbalanced distribution of loads, impaired bone formation, increased pain perception, and risk of fracture, ultimately leading to recurrent surgeries. In the past decade, research efforts have been focused on the development of innovative bone substitutes that not only provide immediate mechanical support, but also ensure appropriate graft anchoring by, for example, promoting bone tissue formation.

The synergistic effect of low oxygen tension and macromolecular crowding in the development of extracellular matrix-rich tendon equivalents.

Cellular therapies play an important role in tendon tissue engineering, with tenocytes being the most prominent and potent cell population available. However, for the development of a rich extracellular matrix tenocyte-assembled tendon equivalent, prolonged in vitro culture is required, which is associated with phenotypic drift. Recapitulation of tendon tissue microenvironment in vitro with cues that enhance and accelerate extracellular matrix synthesis and deposition, whilst maintaining tenocyte phenotype, may lead to functional cell therapies.

Production and Characterization of Chemically Cross-Linked Collagen Scaffolds.

Chemical cross-linking of collagen-based devices is used as a means of increasing the mechanical stability and control the degradation rate upon implantation. Herein, we describe techniques to produce cross-linked with glutaraldehyde (GTA; amine terminal cross-linker), 4-arm polyethylene glycol succinimidyl glutarate (4SP; amine terminal cross-linker), diphenyl phosphoryl azide (DPPA; carboxyl terminal cross-linker), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC; carboxyl terminal cross-linker) collagen films. In addition, we provide protocols to characterize the biophysical (swelling), biomechanical (tensile), and biological (metabolic activity, proliferation and viability using human dermal fibroblasts and THP-1 macrophages) properties of the cross-linked collagen scaffolds.

UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells.

Dendritic cells (DC) have the unique ability to present exogenous antigens via the major histocompatibility complex class I pathway to stimulate naive CD8 T cells. In DCs with a non-functional mutation in Unc93b1 (3d mutation), endosomal acidification, phagosomal maturation, antigen degradation, antigen export to the cytosol and the function of the store-operated-Ca-entry regulator STIM1 are impaired. These defects result in compromised antigen cross-presentation and anti-tumor responses in 3d-mutated mice.