Reproducible lung protective effects of a TGFβR1/ALK5 inhibitor in a bleomycin-induced and spirometry-confirmed model of IPF in male mice.

This study comprehensively validated the bleomycin (BLEO) induced mouse model of IPF for utility in preclinical drug discovery. To this end, the model was rigorously evaluated for reproducible phenotype and TGFβ-directed treatment outcomes. Lung disease was profiled longitudinally in male C57BL6/JRJ mice receiving a single intratracheal instillation of BLEO (n = 10-12 per group).

Histological and immunohistochemical guide to tendon tissue.

Tendons are unique dense connective tissues with discrete zones having specific structure and function. They are juxtaposed with other tissues (e.g.

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.

Macromolecular crowding in animal component-free, xeno-free and foetal bovine serum media for human bone marrow mesenchymal stromal cell expansion and differentiation.

Cell culture media containing undefined animal-derived components and prolonged culture periods in the absence of native extracellular matrix result in phenotypic drift of human bone marrow stromal cells (hBMSCs). Herein, we assessed whether animal component-free (ACF) or xeno-free (XF) media formulations maintain hBMSC phenotypic characteristics more effectively than foetal bovine serum (FBS)-based media. In addition, we assessed whether tissue-specific extracellular matrix, induced macromolecular crowding (MMC) during expansion and/or differentiation, can more tightly control hBMSC fate.

Assessing the combined effect of surface topography and substrate rigidity in human bone marrow stem cell cultures.

The combined effect of surface topography and substrate rigidity in stem cell cultures is still under-investigated, especially when biodegradable polymers are used. Herein, we assessed human bone marrow stem cell response on aliphatic polyester substrates as a function of anisotropic grooved topography and rigidity (7 and 12 kPa). Planar tissue culture plastic (TCP, 3 GPa) and aliphatic polyester substrates were used as controls.

Craniofacial tendon development-Characterization of extracellular matrix morphology and spatiotemporal protein distribution.

Craniofacial (CF) tendons are often affected by traumatic injuries and painful disorders that can severely compromise critical jaw functions, such as mastication and talking. Unfortunately, tendons lack the ability to regenerate, and there are no solutions to restore their native properties or function. An understanding of jaw tendon development could inform tendon regeneration strategies to restore jaw function, however CF tendon development has been relatively unexplored.

Macromolecular crowding transforms regenerative medicine by enabling the accelerated development of functional and truly three-dimensional cell assembled micro tissues.

Scaffold-free in vitro organogenesis exploits the innate ability of cells to synthesise and deposit their own extracellular matrix to fabricate tissue-like assemblies. Unfortunately, cell-assembled tissue engineered concepts require prolonged ex vivo culture periods of very high cell numbers for the development of a borderline three-dimensional implantable device, which are associated with phenotypic drift and high manufacturing costs, thus, hindering their clinical translation and commercialisation. Herein, we report the accelerated (10 days) development of a truly three-dimensional (338.

The Influence of Bloom Index, Endotoxin Levels and Polyethylene Glycol Succinimidyl Glutarate Crosslinking on the Physicochemical and Biological Properties of Gelatin Biomaterials.

In the medical device sector, bloom index and residual endotoxins should be controlled, as they are crucial regulators of the device's physicochemical and biological properties. It is also imperative to identify a suitable crosslinking method to increase mechanical integrity, without jeopardising cellular functions of gelatin-based devices. Herein, gelatin preparations with variable bloom index and endotoxin levels were used to fabricate non-crosslinked and polyethylene glycol succinimidyl glutarate crosslinked gelatin scaffolds, the physicochemical and biological properties of which were subsequently assessed.

Hyaluronic Acid as Macromolecular Crowder in Equine Adipose-Derived Stem Cell Cultures.

The use of macromolecular crowding in the development of extracellular matrix-rich cell-assembled tissue equivalents is continuously gaining pace in regenerative engineering. Despite the significant advancements in the field, the optimal macromolecular crowder still remains elusive. Herein, the physicochemical properties of different concentrations of different molecular weights hyaluronic acid (HA) and their influence on equine adipose-derived stem cell cultures were assessed.

Extracellular matrix-based biomaterials as adipose-derived stem cell delivery vehicles in wound healing: a comparative study between a collagen scaffold and two xenografts.

Background: Stem cell therapies represent a promising tool in regenerative medicine. Considering the drawbacks of direct stem cell injections (e.g.

Seaweed polysaccharides as macromolecular crowding agents.

Development of mesenchymal stem cell-based tissue engineered implantable devices requires prolonged in vitro culture for the development of a three-dimensional implantable device, which leads to phenotypic drift, thus hindering the clinical translation and commercialisation of such approaches. Macromolecular crowding, a biophysical phenomenon based on the principles of excluded-volume effect, dramatically accelerates and increases extracellular matrix deposition during in vitro culture. However, the optimal macromolecular crowder is still elusive.

Global Responses of Il-1β-Primed 3D Tendon Constructs to Treatment with Pulsed Electromagnetic Fields.

Tendinopathy is accompanied by a cascade of inflammatory events promoting tendon degeneration. Among various cytokines, interleukin-1β plays a central role in driving catabolic processes, ultimately resulting in the activation of matrix metalloproteinases and a diminished collagen synthesis, both of which promote tendon extracellular matrix degradation. Pulsed electromagnetic field (PEMF) therapy is often used for pain management, osteoarthritis, and delayed wound healing.

Bevacizumab Improves Achilles Tendon Repair in a Rat Model.

Background/aims: Effective wound-healing generally requires efficient re-vascularization after injury, ensuring sufficient supply with oxygen, nutrients, and various cell populations. While this applies to most tissues, tendons are mostly avascular in nature and harbor relatively few cells, probably contributing to their poor regenerative capacity. Considering the minimal vascularization of healthy tendons, we hypothesize that controlling angiogenesis in early tendon healing is beneficial for repair tissue quality and function.

Limiting angiogenesis to modulate scar formation.

Angiogenesis, the process of new blood vessel formation from existing blood vessels, is a key aspect of virtually every repair process. During wound healing an extensive, but immature and leaky vascular plexus forms which is subsequently reduced by regression of non-functional vessels. More recent studies indicate that uncontrolled vessel growth or impaired vessel regression as a consequence of an excessive inflammatory response can impair wound healing, resulting in scarring and dysfunction.

A high-glucose diet affects Achilles tendon healing in rats.

Chronic and acute tendinopathies are difficult to treat and tendon healing is generally a very slow and incomplete process and our general understanding of tendon biology and regeneration lags behind that of muscle or bone. Although still largely unexplored, several studies suggest a positive effect of nutritional interventions on tendon health and repair. With this study, we aim to reveal effects of a high-glucose diet on tendon neoformation in a non-diabetic rat model of Achilles tenotomy.

Comparing the osteogenic potential of bone marrow and tendon-derived stromal cells to repair a critical-sized defect in the rat femur.

Despite significant advancements in bone tissue-engineering applications, the clinical impact of bone marrow stromal cells (BMSCs) for the treatment of large osseous defects remains limited. Therefore, other cell sources are under investigation for their osteogenic potential to repair bone. In this study, tendon-derived stromal cells (TDSCs) were evaluated in comparison to BMSCs to support the functional repair of a 5 mm critical-sized, segmental defect in the rat femur.

Presence of lymphatics in a rat tendon lesion model.

Tendons lack sufficient blood supply and represent a bradytroph tissue with prolonged healing time under pathological conditions. While the role of lymphatics in wound/defect healing in tissues with regular blood supply is well investigated, its involvement in tendon defects is not clear. We here try to identify the role of the lymphatic system in a tendon lesion model with morphological methods.

ACL injuries and stem cell therapy.

Tears of the anterior cruciate ligament (ACL) are very frequent injuries, particularly in young and active people. Arthroscopic reconstruction using tendon auto- or allograft represents the gold-standard for the management of ACL tears. Interestingly, the ACL has the potential to heal upon intensive non-surgical rehabilitation procedures.

Neural crest origin of retinal and choroidal pericytes.

Purpose: The origin of pericytes (PCs) has been controversially discussed and at least three different sources of PCs are proposed: a neural crest, mesodermal, or bone marrow origin. In the present study we investigated a potential neural crest origin of ocular PCs in a transgenic Rosa26-YFP-Sox10-Cre neural crest-specific reporter mouse model at different developmental stages.

Methods: The Rosa26-YFP-Sox10-Cre mouse model expresses the yellow fluorescent protein (YFP) reporter in cells with an active Sox10 promoter and was here used for cell fate studies of Sox10-positive neural crest derived progeny cells.